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Sample records for brain stem implant

  1. Lymphoscintigraphy and autologous stem cell implantation

    International Nuclear Information System (INIS)

    Peña, Yamile; Batista, Juan F.; Perera, Alejandro; Torres, Leonel A.; Sánchez, Elvia L.; Sánchez, Yolaine; Ducat, Luis; Prats, Anais; Hernández, Porfirio; Romero, Susana; Goicochea, Pedro; Quintela, Ana M.

    2016-01-01

    Lymphoscintigraphy is the criterion standard technique for the diagnosis of lymphedema. Advances of the application of autologous hematopoietic stem cells in ischemic disorders of lower limbs have increased the attention of researchers in this field. Aim: To determine the usefulness of lymphoscintigraphy for the assessment the efficacy of autologous stem cell implantation in patients with chronic lymphedema of the upper and lower limbs. Methods: Sixty-five patients were included. Clinical evaluation and lymphoscintigraphy were performed before and six months after stem cells implantation. The stem cells implantations were carried out by multiple superficial and deep injections in the trajectory of the lymphatic vessels and also in the inguinal region. A volume of 0.75 to 1.00 mL of cell suspension (1.0-2.2 x 109 stem cells) was administered in each injection site. Lymphoscintigraphy: Whole-body scans were acquired at 20 minutes, 1 hour, and 3 hours after administration of 185 to 259 MBq (5–7mCi) of 99m Tc-albumin nanocolloids in the interdigital space of both limbs. The anatomy and function of the lymphatic system were evaluated. Results: Functional assessment before implantation of stem cells showed that 69.2% of the patients had severe lymphatic insufficiency. The 61.5% of patients showed clinical improvement, confirmed by the results of the lymphoscintigraphy. The 46.1% of the cases evaluated showed a clear improvement. The study showed that the isotopic lymphography can evaluate the therapeutic response and its intensity. Conclusion: Lymphoscintigraphy is a useful technique for the evaluation and monitoring of autologous stem cell transplantation in patients with chronic lymphedema. (author)

  2. Transcranial magnetic stimulation of human adult stem cells in the mammalian brain

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    Karlea L Kremer

    2016-03-01

    Full Text Available Introduction: The burden of stroke on the community is growing, and therefore, so is the need for a therapy to overcome the disability following stroke. Cellular-based therapies are being actively investigated at a pre-clinical and clinical level. Studies have reported the beneficial effects of exogenous stem cell implantation, however, these benefits are also associated with limited survival of implanted stem cells. This exploratory study investigated the use of transcranial magnetic stimulation (TMS as a complementary therapy to increase stem cell survival following implantation of human dental pulp stem cells (DPSC in the rodent cortex. Methods: Sprague-Dawley rats were anaesthetised and injected with 6x105 DPSC or control media via an intracranial injection, and then received real TMS (TMS0.2Hz or sham TMS (TMSsham every 2nd day beginning on day 3 post DPSC injection for 2 weeks. Brain sections were analysed for the survival, migration and differentiation characteristics of the implanted cells. Results: In animals treated with DPSC and TMS0.2Hz there were significantly less implanted DPSC and those that survived remained in the original cerebral hemisphere compared to animals that received TMSsham. The surviving implanted DPSC in TMS0.2Hz were also found to express the apoptotic marker Caspase-3. Conclusions: We suggest that TMS at this intensity may cause an increase in glutamate levels, which promotes an unfavourable environment for stem cell implantation, proliferation and differentiation. It should be noted that only one paradigm of TMS was tested as this was conducted as an exploratory study, and further TMS paradigms should be investigated in the future.

  3. Sensorimotor Functional and Structural Networks after Intracerebral Stem Cell Grafts in the Ischemic Mouse Brain.

    Science.gov (United States)

    Green, Claudia; Minassian, Anuka; Vogel, Stefanie; Diedenhofen, Michael; Beyrau, Andreas; Wiedermann, Dirk; Hoehn, Mathias

    2018-02-14

    Past investigations on stem cell-mediated recovery after stroke have limited their focus on the extent and morphological development of the ischemic lesion itself over time or on the integration capacity of the stem cell graft ex vivo However, an assessment of the long-term functional and structural improvement in vivo is essential to reliably quantify the regenerative capacity of cell implantation after stroke. We induced ischemic stroke in nude mice and implanted human neural stem cells (H9 derived) into the ipsilateral cortex in the acute phase. Functional and structural connectivity changes of the sensorimotor network were noninvasively monitored using magnetic resonance imaging for 3 months after stem cell implantation. A sharp decrease of the functional sensorimotor network extended even to the contralateral hemisphere, persisting for the whole 12 weeks of observation. In mice with stem cell implantation, functional networks were stabilized early on, pointing to a paracrine effect as an early supportive mechanism of the graft. This stabilization required the persistent vitality of the stem cells, monitored by bioluminescence imaging. Thus, we also observed deterioration of the early network stabilization upon vitality loss of the graft after a few weeks. Structural connectivity analysis showed fiber-density increases between the cortex and white matter regions occurring predominantly on the ischemic hemisphere. These fiber-density changes were nearly the same for both study groups. This motivated us to hypothesize that the stem cells can influence, via early paracrine effect, the functional networks, while observed structural changes are mainly stimulated by the ischemic event. SIGNIFICANCE STATEMENT In recent years, research on strokes has made a shift away from a focus on immediate ischemic effects and towards an emphasis on the long-range effects of the lesion on the whole brain. Outcome improvements in stem cell therapies also require the understanding of

  4. Traumatic primary brain stem haemorrhage

    International Nuclear Information System (INIS)

    Andrioli, G.C.; Zuccarello, M.; Trincia, G.; Fiore, D.L.; De Caro, R.

    1983-01-01

    We report 36 cases of post-traumatic 'primary brain stem haemorrhage' visualized by the CT scan and confirmed at autopsy. Clinical experience shows that many technical factors influence the inability to visualize brain stem haemorrhages. Experimental injection of fresh blood into the pons and midbrain of cadavers shows that lesions as small as 0.25 ml in volume may be visualized. The volume and the anatomical configuration of traumatic lesions of the brain stem extended over a rostro-caudal direction, and their proximity to bony structures at the base of the skull are obstacles to the visualization of brain stem haemorrhages. (Author)

  5. The stem cell secretome and its role in brain repair.

    Science.gov (United States)

    Drago, Denise; Cossetti, Chiara; Iraci, Nunzio; Gaude, Edoardo; Musco, Giovanna; Bachi, Angela; Pluchino, Stefano

    2013-12-01

    Compelling evidence exists that non-haematopoietic stem cells, including mesenchymal (MSCs) and neural/progenitor stem cells (NPCs), exert a substantial beneficial and therapeutic effect after transplantation in experimental central nervous system (CNS) disease models through the secretion of immune modulatory or neurotrophic paracrine factors. This paracrine hypothesis has inspired an alternative outlook on the use of stem cells in regenerative neurology. In this paradigm, significant repair of the injured brain may be achieved by injecting the biologics secreted by stem cells (secretome), rather than implanting stem cells themselves for direct cell replacement. The stem cell secretome (SCS) includes cytokines, chemokines and growth factors, and has gained increasing attention in recent years because of its multiple implications for the repair, restoration or regeneration of injured tissues. Thanks to recent improvements in SCS profiling and manipulation, investigators are now inspired to harness the SCS as a novel alternative therapeutic option that might ensure more efficient outcomes than current stem cell-based therapies for CNS repair. This review discusses the most recent identification of MSC- and NPC-secreted factors, including those that are trafficked within extracellular membrane vesicles (EVs), and reflects on their potential effects on brain repair. It also examines some of the most convincing advances in molecular profiling that have enabled mapping of the SCS. Copyright © 2013 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  6. Monitoring of implanted stem cell migration in vivo: A highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat

    Science.gov (United States)

    Hoehn, Mathias; Küstermann, Ekkehard; Blunk, James; Wiedermann, Dirk; Trapp, Thorsten; Wecker, Stefan; Föcking, Melanie; Arnold, Heinz; Hescheler, Jürgen; Fleischmann, Bernd K.; Schwindt, Wolfram; Bührle, Christian

    2002-01-01

    In vivo monitoring of stem cells after grafting is essential for a better understanding of their migrational dynamics and differentiation processes and of their regeneration potential. Migration of endogenous or grafted stem cells and neurons has been described in vertebrate brain, both under normal conditions from the subventricular zone along the rostral migratory stream and under pathophysiological conditions, such as degeneration or focal cerebral ischemia. Those studies, however, relied on invasive analysis of brain sections in combination with appropriate staining techniques. Here, we demonstrate the observation of cell migration under in vivo conditions, allowing the monitoring of the cell dynamics within individual animals, and for a prolonged time. Embryonic stem (ES) cells, constitutively expressing the GFP, were labeled by a lipofection procedure with a MRI contrast agent and implanted into rat brains. Focal cerebral ischemia had been induced 2 weeks before implantation of ES cells into the healthy, contralateral hemisphere. MRI at 78-μm isotropic spatial resolution permitted the observation of the implanted cells with high contrast against the host tissue, and was confirmed by GFP registration. During 3 weeks, cells migrated along the corpus callosum to the ventricular walls, and massively populated the borderzone of the damaged brain tissue on the hemisphere opposite to the implantation sites. Our results indicate that ES cells have high migrational dynamics, targeted to the cerebral lesion area. The imaging approach is ideally suited for the noninvasive observation of cell migration, engraftment, and morphological differentiation at high spatial and temporal resolution. PMID:12444255

  7. Osseointegration of a 3D Printed Stemmed Titanium Dental Implant: A Pilot Study

    Directory of Open Access Journals (Sweden)

    James Tedesco

    2017-01-01

    Full Text Available In this pilot study, a 3D printed Grade V titanium dental implant with a novel dual-stemmed design was investigated for its biocompatibility in vivo. Both dual-stemmed (n = 12 and conventional stainless steel conical (n = 4 implants were inserted into the tibial metaphysis of New Zealand white rabbits for 3 and 12 weeks and then retrieved with the surrounding bone, fixed, dehydrated, and embedded into epoxy resin. The implants were analyzed using correlative histology, microcomputed tomography, scanning electron microscopy (SEM, and transmission electron microscopy (TEM. The histological presence of multinucleated osteoclasts and cuboidal osteoblasts revealed active bone remodeling in the stemmed implant starting at 3 weeks and by 12 weeks in the conventional implant. Bone-implant contact values indicated that the stemmed implants supported bone growth along the implant from the coronal crest at both 3- and 12-week time periods and showed bone growth into microporosities of the 3D printed surface after 12 weeks. In some cases, new bone formation was noted in between the stems of the device. Conventional implants showed mechanical interlocking but did have indications of stress cracking and bone debris. This study demonstrates the comparable biocompatibility of these 3D printed stemmed implants in rabbits up to 12 weeks.

  8. Osseointegration of a 3D Printed Stemmed Titanium Dental Implant: A Pilot Study.

    Science.gov (United States)

    Tedesco, James; Lee, Bryan E J; Lin, Alex Y W; Binkley, Dakota M; Delaney, Kathleen H; Kwiecien, Jacek M; Grandfield, Kathryn

    2017-01-01

    In this pilot study, a 3D printed Grade V titanium dental implant with a novel dual-stemmed design was investigated for its biocompatibility in vivo. Both dual-stemmed ( n  = 12) and conventional stainless steel conical ( n  = 4) implants were inserted into the tibial metaphysis of New Zealand white rabbits for 3 and 12 weeks and then retrieved with the surrounding bone, fixed, dehydrated, and embedded into epoxy resin. The implants were analyzed using correlative histology, microcomputed tomography, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The histological presence of multinucleated osteoclasts and cuboidal osteoblasts revealed active bone remodeling in the stemmed implant starting at 3 weeks and by 12 weeks in the conventional implant. Bone-implant contact values indicated that the stemmed implants supported bone growth along the implant from the coronal crest at both 3- and 12-week time periods and showed bone growth into microporosities of the 3D printed surface after 12 weeks. In some cases, new bone formation was noted in between the stems of the device. Conventional implants showed mechanical interlocking but did have indications of stress cracking and bone debris. This study demonstrates the comparable biocompatibility of these 3D printed stemmed implants in rabbits up to 12 weeks.

  9. Paraneoplastic brain stem encephalitis.

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    Blaes, Franz

    2013-04-01

    Paraneoplastic brain stem encephalitis can occur as an isolated clinical syndrome or, more often, may be part of a more widespread encephalitis. Different antineuronal autoantibodies, such as anti-Hu, anti-Ri, and anti-Ma2 can be associated with the syndrome, and the most frequent tumors are lung and testicular cancer. Anti-Hu-associated brain stem encephalitis does not normally respond to immunotherapy; the syndrome may stabilize under tumor treatment. Brain stem encephalitis with anti-Ma2 often improves after immunotherapy and/or tumor therapy, whereas only a minority of anti-Ri positive patients respond to immunosuppressants or tumor treatment. The Opsoclonus-myoclonus syndrome (OMS) in children, almost exclusively associated with neuroblastoma, shows a good response to steroids, ACTH, and rituximab, some patients do respond to intravenous immunoglobulins or cyclophosphamide. In adults, OMS is mainly associated with small cell lung cancer or gynecological tumors and only a small part of the patients show improvement after immunotherapy. Earlier diagnosis and treatment seem to be one major problem to improve the prognosis of both, paraneoplastic brain stem encephalitis, and OMS.

  10. Brain stem type neuro-Behcet's syndrome

    International Nuclear Information System (INIS)

    Kataoka, Satoshi; Hirose, Genjiro; Kosoegawa, Hiroshi; Oda, Rokuhei; Yoshioka, Akira

    1987-01-01

    Two cases of brain stem type Neuro-Behcet's syndrome were evaluated by brain CT and Magnetic Resonance Imaging (Super-conducting type, 0.5 tesla) to correlate with the neurological findings. In the acute phase, low density area with peripheral enhancement effect and mass effect were seen at the brain stem in brain CT. MRI revealed a extensive high intensity signal area mainly involving the corticospinal tract in the meso-diencephalon as well as pons by T 2 weighted images (spin echo, TR = 1, 600 msec, TE = 90 msec) and the value of T 1 , T 2 , at the brain stem lesion were prolonged moderately. After high dose steroid treatment, the low density area in brain CT and high signal area in MRI were gradually reduced in its size. Peripheral enhancement effect in brain CT disappeared within 10 months in case 1, one month in the other case. In the chronic stage, the reduction of low density area and atrophy of brain stem were noted in brain CT. The lesion in chronic stage had low intensity in T 1 , T 2 weighted images and the T 1 , T 2 values at the lesion were mildly prolonged in MRI. Sequentially CT with enhancement and MRI examinations with T 1 , T 2 weighted images were useful to detect the lesion and to evaluate the activity, evolution of brain stem type Neuro-Behcet's syndrome. (author)

  11. Brain mesenchymal stem cells: The other stem cells of the brain?

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    Appaix, Florence; Nissou, Marie-France; van der Sanden, Boudewijn; Dreyfus, Matthieu; Berger, François; Issartel, Jean-Paul; Wion, Didier

    2014-04-26

    Multipotent mesenchymal stromal cells (MSC), have the potential to differentiate into cells of the mesenchymal lineage and have non-progenitor functions including immunomodulation. The demonstration that MSCs are perivascular cells found in almost all adult tissues raises fascinating perspectives on their role in tissue maintenance and repair. However, some controversies about the physiological role of the perivascular MSCs residing outside the bone marrow and on their therapeutic potential in regenerative medicine exist. In brain, perivascular MSCs like pericytes and adventitial cells, could constitute another stem cell population distinct to the neural stem cell pool. The demonstration of the neuronal potential of MSCs requires stringent criteria including morphological changes, the demonstration of neural biomarkers expression, electrophysiological recordings, and the absence of cell fusion. The recent finding that brain cancer stem cells can transdifferentiate into pericytes is another facet of the plasticity of these cells. It suggests that the perversion of the stem cell potential of pericytes might play an even unsuspected role in cancer formation and tumor progression.

  12. The effect of distal ulnar implant stem material and length on bone strains.

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    Austman, Rebecca L; Beaton, Brendon J B; Quenneville, Cheryl E; King, Graham J W; Gordon, Karen D; Dunning, Cynthia E

    2007-01-01

    Implant design parameters can greatly affect load transfer from the implant stem to the bone. We have investigated the effect of length or material of distal ulnar implant stems on the surrounding bone strains. Eight cadaveric ulnas were instrumented with 12 strain gauges and secured in a customized jig. Strain data were collected while loads (5-30 N) were applied to the medial surface of the native ulnar head. The native ulnar head was removed, and a stainless steel implant with an 8-cm-long finely threaded stem was cemented into the canal. After the cement had cured, the 8-cm stem was removed, leaving a threaded cement mantle in the canal that could accept shorter threaded stems of interest. The loading protocol was then repeated for stainless steel stems that were 7, 5, and 3 cm in length, as well as for a 5-cm-long titanium alloy (TiAl(6)V(4)) stem. Other stainless steel stem lengths between 3 and 7 cm were tested at intervals of 0.5 cm, with only a 20 N load applied. No stem length tested matched the native strains at all gauge locations. No significant differences were found between any stem length and the native bone at the 5th and 6th strain gauge positions. Strains were consistently closer to the native bone strains with the titanium stem than the stainless steel stem for each gauge pair that was positioned on the bone overlying the stem. The 3-cm stem results were closer to the native strains than the 7-cm stem for all loads at gauges locations that were on top of the stem. The results from this study suggest that the optimal stem characteristics for distal ulnar implants from a load transfer point of view are possessed by shorter (approximately 3 to 4 cm) titanium stems.

  13. Neurofibromatosis type 1: brain stem tumours

    International Nuclear Information System (INIS)

    Bilaniuk, L.T.; Molloy, P.T.; Zimmerman, R.A.; Phillips, P.C.; Vaughan, S.N.; Liu, G.T.; Sutton, L.N.; Needle, M.

    1997-01-01

    We describe the clinical and imaging findings of brain stem tumours in patients with neurofibromatosis type 1 (NF1). The NF1 patients imaged between January 1984 and January 1996 were reviewed and 25 patients were identified with a brain stem tumour. Clinical, radiographical and pathological results were obtained by review of records and images. Brain stem tumour identification occurred much later than the clinical diagnosis of NF1. Medullary enlargement was most frequent (68 %), followed by pontine (52 %) and midbrain enlargement (44 %). Patients were further subdivided into those with diffuse (12 patients) and those with focal (13 patients) tumours. Treatment for hydrocephalus was required in 67 % of the first group and only 15 % of the second group. Surgery was performed in four patients and revealed fibrillary astrocytomas, one of which progressed to an anaplastic astrocytoma. In 40 % of patients both brain stem and optic pathway tumours were present. The biological behaviour of brain stem tumours in NF1 is unknown. Diffuse tumours in the patients with NF1 appear to have a much more favourable prognosis than patients with similar tumours without neurofibromatosis type 1. (orig.). With 7 figs., 3 tabs

  14. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model.

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    Stine Skov Jensen

    Full Text Available Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking invasion and tumor stemness into account.Glioblastoma stem cell-like containing spheroid (GSS cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models.We observed a pronounced invasion into brain slice cultures both by confocal time-lapse microscopy and immunohistochemistry. This invasion closely resembled the invasion in vivo. The Ki-67 proliferation indexes in spheroids implanted into brain slices were lower than in free-floating spheroids. The expression of stem cell markers varied between free-floating spheroids, spheroids implanted into brain slices and tumors in vivo.The established invasion model kept in stem cell medium closely mimics tumor cell invasion into the brain in vivo preserving also to some extent the expression of stem cell markers. The model is feasible and robust and we suggest the model as an in vivo-like model with a great potential in glioma studies and drug discovery.

  15. Machine learning techniques for the optimization of joint replacements: Application to a short-stem hip implant.

    Science.gov (United States)

    Cilla, Myriam; Borgiani, Edoardo; Martínez, Javier; Duda, Georg N; Checa, Sara

    2017-01-01

    Today, different implant designs exist in the market; however, there is not a clear understanding of which are the best implant design parameters to achieve mechanical optimal conditions. Therefore, the aim of this project was to investigate if the geometry of a commercial short stem hip prosthesis can be further optimized to reduce stress shielding effects and achieve better short-stemmed implant performance. To reach this aim, the potential of machine learning techniques combined with parametric Finite Element analysis was used. The selected implant geometrical parameters were: total stem length (L), thickness in the lateral (R1) and medial (R2) and the distance between the implant neck and the central stem surface (D). The results show that the total stem length was not the only parameter playing a role in stress shielding. An optimized implant should aim for a decreased stem length and a reduced length of the surface in contact with the bone. The two radiuses that characterize the stem width at the distal cross-section in contact with the bone were less influential in the reduction of stress shielding compared with the other two parameters; but they also play a role where thinner stems present better results.

  16. Childhood Brain Stem Glioma Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Childhood brain stem glioma can be a benign (not cancer) or malignant (cancer) condition where abnormal cells form in the tissues of the brain stem. Get information about the symptoms, diagnosis, prognosis, and treatment of newly diagnosed and recurrent childhood brain stem glioma in this expert-reviewed summary.

  17. Brain stem cavernous angioma

    International Nuclear Information System (INIS)

    Delcarpio-O'Donovan, R.; Melanson, D.; Tampieri, D.; Ethier, R.

    1988-01-01

    Twenty-two cases of cavernous angioma of the brain stem were definitely diagnosed by means of magnetic resonance (MR) imaging. In many cases, the diagnosis had remained elusive for several years. Clinically, some cases behaved like multiple sclerosis or brain stem tumor. Others, usually associated with bleeding, caused increased intracranial pressure or subarachnoid hemorrhage. The diagnostic limitations of computed tomography in the posterior fossa are well known. Angiography fails to reveal abnormalities, since this malformation has neither a feeding artery nor a draining vein. Diagnosticians' familiarity with the MR appearance of this lesion may save patients from invasive diagnostic studies and potentially risky treatment

  18. Failure of Emperion modular femoral stem with implant analysis

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    Benjamin M. Stronach, MD, MS

    2016-03-01

    Full Text Available Modularity in total hip arthroplasty provides multiple benefits to the surgeon in restoring the appropriate alignment and position to a previously damaged hip joint. The vast majority of modern implants incorporate modularity into their design with some implants having multiple modular interfaces. There is the potential for failure at modular junctions because of fretting and crevice corrosion in combination with mechanical loading. This case report details the failure of an Emperion (Smith and Nephew, Memphis, TN femoral stem in a 67-year-old male patient 6 years after total hip replacement. Analysis of the implant revealed mechanically assisted crevice corrosion that likely accelerated fatigue crack initiation in the hip stem. The benefits of modularity come with the potential drawback of a combination of fretting and crevice corrosion at the modular junction, which may accelerate fatigue, crack initiation and ultimately reduce the hip longevity.

  19. Modeling Stem/Progenitor Cell-Induced Neovascularization and Oxygenation Around Solid Implants

    KAUST Repository

    Jain, Harsh Vardhan

    2012-07-01

    Tissue engineering constructs and other solid implants with biomedical applications, such as drug delivery devices or bioartificial organs, need oxygen (O(2)) to function properly. To understand better the vascular integration of such devices, we recently developed a novel model sensor containing O(2)-sensitive crystals, consisting of a polymeric capsule limited by a nanoporous filter. The sensor was implanted in mice with hydrogel alone (control) or hydrogel embedded with mouse CD117/c-kit+ bone marrow progenitor cells in order to stimulate peri-implant neovascularization. The sensor provided local partial O(2) pressure (pO(2)) using noninvasive electron paramagnetic resonance signal measurements. A consistently higher level of peri-implant oxygenation was observed in the cell-treatment case than in the control over a 10-week period. To provide a mechanistic explanation of these experimental observations, we present in this article a mathematical model, formulated as a system of coupled partial differential equations, that simulates peri-implant vascularization. In the control case, vascularization is considered to be the result of a foreign body reaction, while in the cell-treatment case, adipogenesis in response to paracrine stimuli produced by the stem cells is assumed to induce neovascularization. The model is validated by fitting numerical predictions of local pO(2) to measurements from the implanted sensor. The model is then used to investigate further the potential for using stem cell treatment to enhance the vascular integration of biomedical implants. We thus demonstrate how mathematical modeling combined with experimentation can be used to infer how vasculature develops around biomedical implants in control and stem cell-treated cases.

  20. Modeling Stem/Progenitor Cell-Induced Neovascularization and Oxygenation Around Solid Implants

    KAUST Repository

    Jain, Harsh Vardhan; Moldovan, Nicanor I.; Byrne, Helen M.

    2012-01-01

    Tissue engineering constructs and other solid implants with biomedical applications, such as drug delivery devices or bioartificial organs, need oxygen (O(2)) to function properly. To understand better the vascular integration of such devices, we recently developed a novel model sensor containing O(2)-sensitive crystals, consisting of a polymeric capsule limited by a nanoporous filter. The sensor was implanted in mice with hydrogel alone (control) or hydrogel embedded with mouse CD117/c-kit+ bone marrow progenitor cells in order to stimulate peri-implant neovascularization. The sensor provided local partial O(2) pressure (pO(2)) using noninvasive electron paramagnetic resonance signal measurements. A consistently higher level of peri-implant oxygenation was observed in the cell-treatment case than in the control over a 10-week period. To provide a mechanistic explanation of these experimental observations, we present in this article a mathematical model, formulated as a system of coupled partial differential equations, that simulates peri-implant vascularization. In the control case, vascularization is considered to be the result of a foreign body reaction, while in the cell-treatment case, adipogenesis in response to paracrine stimuli produced by the stem cells is assumed to induce neovascularization. The model is validated by fitting numerical predictions of local pO(2) to measurements from the implanted sensor. The model is then used to investigate further the potential for using stem cell treatment to enhance the vascular integration of biomedical implants. We thus demonstrate how mathematical modeling combined with experimentation can be used to infer how vasculature develops around biomedical implants in control and stem cell-treated cases.

  1. Modeling Stem/Progenitor Cell-Induced Neovascularization and Oxygenation Around Solid Implants

    Science.gov (United States)

    Moldovan, Nicanor I.; Byrne, Helen M.

    2012-01-01

    Tissue engineering constructs and other solid implants with biomedical applications, such as drug delivery devices or bioartificial organs, need oxygen (O2) to function properly. To understand better the vascular integration of such devices, we recently developed a novel model sensor containing O2-sensitive crystals, consisting of a polymeric capsule limited by a nanoporous filter. The sensor was implanted in mice with hydrogel alone (control) or hydrogel embedded with mouse CD117/c-kit+ bone marrow progenitor cells in order to stimulate peri-implant neovascularization. The sensor provided local partial O2 pressure (pO2) using noninvasive electron paramagnetic resonance signal measurements. A consistently higher level of peri-implant oxygenation was observed in the cell-treatment case than in the control over a 10-week period. To provide a mechanistic explanation of these experimental observations, we present in this article a mathematical model, formulated as a system of coupled partial differential equations, that simulates peri-implant vascularization. In the control case, vascularization is considered to be the result of a foreign body reaction, while in the cell-treatment case, adipogenesis in response to paracrine stimuli produced by the stem cells is assumed to induce neovascularization. The model is validated by fitting numerical predictions of local pO2 to measurements from the implanted sensor. The model is then used to investigate further the potential for using stem cell treatment to enhance the vascular integration of biomedical implants. We thus demonstrate how mathematical modeling combined with experimentation can be used to infer how vasculature develops around biomedical implants in control and stem cell-treated cases. PMID:22224628

  2. Osseointegration of a 3D Printed Stemmed Titanium Dental Implant: A Pilot Study

    OpenAIRE

    James Tedesco; Bryan E. J. Lee; Alex Y. W. Lin; Dakota M. Binkley; Kathleen H. Delaney; Jacek M. Kwiecien; Kathryn Grandfield

    2017-01-01

    In this pilot study, a 3D printed Grade V titanium dental implant with a novel dual-stemmed design was investigated for its biocompatibility in vivo. Both dual-stemmed (n = 12) and conventional stainless steel conical (n = 4) implants were inserted into the tibial metaphysis of New Zealand white rabbits for 3 and 12 weeks and then retrieved with the surrounding bone, fixed, dehydrated, and embedded into epoxy resin. The implants were analyzed using correlative histology, microcomputed tomogra...

  3. Training stem cells for treatment of malignant brain tumors

    Institute of Scientific and Technical Information of China (English)

    Shengwen; Calvin; Li; Mustafa; H; Kabeer; Long; T; Vu; Vic; Keschrumrus; Hong; Zhen; Yin; Brent; A; Dethlefs; Jiang; F; Zhong; John; H; Weiss; William; G; Loudon

    2014-01-01

    The treatment of malignant brain tumors remains a challenge. Stem cell technology has been applied in the treatment of brain tumors largely because of the ability of some stem cells to infiltrate into regions within the brain where tumor cells migrate as shown in preclinical studies. However, not all of these efforts can translate in the effective treatment that improves the quality of life for pa-tients. Here, we perform a literature review to identify the problems in the field. Given the lack of efficacy of most stem cell-based agents used in the treatment of malignant brain tumors, we found that stem cell distribution(i.e., only a fraction of stem cells applied capable of targeting tumors) are among the limiting factors. We provide guidelines for potential improvements in stem cell distribution. Specifically, we use an engineered tissue graft platform that replicates the in vivo microenvironment, and provide our data to validate that this culture platform is viable for producing stem cells that have better stem cell distribution than with the Petri dish culture system.

  4. Electrical Guidance of Human Stem Cells in the Rat Brain

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    Jun-Feng Feng

    2017-07-01

    Full Text Available Limited migration of neural stem cells in adult brain is a roadblock for the use of stem cell therapies to treat brain diseases and injuries. Here, we report a strategy that mobilizes and guides migration of stem cells in the brain in vivo. We developed a safe stimulation paradigm to deliver directional currents in the brain. Tracking cells expressing GFP demonstrated electrical mobilization and guidance of migration of human neural stem cells, even against co-existing intrinsic cues in the rostral migration stream. Transplanted cells were observed at 3 weeks and 4 months after stimulation in areas guided by the stimulation currents, and with indications of differentiation. Electrical stimulation thus may provide a potential approach to facilitate brain stem cell therapies.

  5. Biology of teeth and implants: Host factors - pathology, regeneration, and the role of stem cells.

    Science.gov (United States)

    Eggert, F-Michael; Levin, Liran

    2018-01-01

    In chronic periodontitis and peri-implantitis, cells of the innate and adaptive immune systems are involved directly in the lesions within the tissues of the patient. Absence of a periodontal ligament around implants does not prevent a biologic process similar to that of periodontitis from affecting osseointegration. Our first focus is on factors in the biology of individuals that are responsible for the susceptibility of such individuals to chronic periodontitis and to peri-implantitis. Genetic factors are of significant importance in susceptibility to these diseases. Genetic factors of the host affect the composition of the oral microbiome in the same manner that they influence other microbiomes, such as those of the intestines and of the lungs. Our second focus is on the central role of stem cells in tissue regeneration, in the functioning of innate and adaptive immune systems, and in metabolism of bone. Epithelial cell rests of Malassez (ERM) are stem cells of epithelial origin that maintain the periodontal ligament as well as the cementum and alveolar bone associated with the ligament. The tissue niche within which ERM are found extends into the supracrestal areas of collagen fiber-containing tissues of the gingivae above the bony alveolar crest. Maintenance and regeneration of all periodontal tissues involves the activity of a variety of stem cells. The success of dental implants indicates that important groups of stem cells in the periodontium are active to enable that biologic success. Successful replantation of avulsed teeth and auto-transplantation of teeth is comparable to placing dental implants, and so must also involve periodontal stem cells. Biology of teeth and biology of implants represents the biology of the various stem cells that inhabit specialized niches within the periodontal tissues. Diverse biologic processes must function together successfully to maintain periodontal health. Osseointegration of dental implants does not involve formation of

  6. Combination cell therapy with mesenchymal stem cells and neural stem cells for brain stroke in rats.

    Science.gov (United States)

    Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

    2015-05-01

    Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.

  7. Stem cells for brain repair in neonatal hypoxia-ischemia.

    Science.gov (United States)

    Chicha, L; Smith, T; Guzman, R

    2014-01-01

    Neonatal hypoxic-ischemic insults are a significant cause of pediatric encephalopathy, developmental delays, and spastic cerebral palsy. Although the developing brain's plasticity allows for remarkable self-repair, severe disruption of normal myelination and cortical development upon neonatal brain injury are likely to generate life-persisting sensory-motor and cognitive deficits in the growing child. Currently, no treatments are available that can address the long-term consequences. Thus, regenerative medicine appears as a promising avenue to help restore normal developmental processes in affected infants. Stem cell therapy has proven effective in promoting functional recovery in animal models of neonatal hypoxic-ischemic injury and therefore represents a hopeful therapy for this unmet medical condition. Neural stem cells derived from pluripotent stem cells or fetal tissues as well as umbilical cord blood and mesenchymal stem cells have all shown initial success in improving functional outcomes. However, much still remains to be understood about how those stem cells can safely be administered to infants and what their repair mechanisms in the brain are. In this review, we discuss updated research into pathophysiological mechanisms of neonatal brain injury, the types of stem cell therapies currently being tested in this context, and the potential mechanisms through which exogenous stem cells might interact with and influence the developing brain.

  8. Characterization of Cancer Stem Cells in Patients with Brain ...

    African Journals Online (AJOL)

    Background: Gliomas, in general, and astrocytomas, in particular, represent the most frequent primary brain tumors. Nowadays, it is increasingly believed that gliomas may arise from cancer stem cells, which share several characteristics with normal neural stem cells. Brain tumor stem cells have been found to express a ...

  9. Magnetic resonance imaging in brain-stem tumors

    International Nuclear Information System (INIS)

    Nomura, Mikio; Saito, Hisazumi; Akino, Minoru; Abe, Hiroshi.

    1988-01-01

    Four patients with brain-stem tumors underwent magnetic resonance imaging (MRI) before and after radiotherapy. The brain-stem tumors were seen as a low signal intensity on T1-weighted images and as a high signal intensity on T2-weighted images. A tumor and its anatomic involvement were more clearly visualized on MRI than on cuncurrently performed CT. Changes in tumor before and after radiotherapy could be determined by measuring the diameter of tumor on sagittal and coronal images. This allowed quantitative evaluation of the reduction of tumor in association with improvement of symptoms. The mean T1 value in the central part of tumors was shortened in all patients after radiotherapy. The results indicate that MRI may assist in determining the effect of radiotherapy for brain-stem tumors. (Namekawa, K)

  10. The Potential of Stem Cells in Treatment of Traumatic Brain Injury.

    Science.gov (United States)

    Weston, Nicole M; Sun, Dong

    2018-01-25

    Traumatic brain injury (TBI) is a global public health concern, with limited treatment options available. Despite improving survival rate after TBI, treatment is lacking for brain functional recovery and structural repair in clinic. Recent studies have suggested that the mature brain harbors neural stem cells which have regenerative capacity following brain insults. Much progress has been made in preclinical TBI model studies in understanding the behaviors, functions, and regulatory mechanisms of neural stem cells in the injured brain. Different strategies targeting these cell population have been assessed in TBI models. In parallel, cell transplantation strategy using a wide range of stem cells has been explored for TBI treatment in pre-clinical studies and some in clinical trials. This review summarized strategies which have been explored to enhance endogenous neural stem cell-mediated regeneration and recent development in cell transplantation studies for post-TBI brain repair. Thus far, neural regeneration through neural stem cells either by modulating endogenous neural stem cells or by stem cell transplantation has attracted much attention. It is highly speculated that targeting neural stem cells could be a potential strategy to repair and regenerate the injured brain. Neuroprotection and neuroregeneration are major aspects for TBI therapeutic development. With technique advancement, it is hoped that stem cell-based therapy targeting neuroregeneration will be able to translate to clinic in not so far future.

  11. Wallerian degeneration of the corticospinal tract in the brain stem

    International Nuclear Information System (INIS)

    Uchino, Akira; Onomura, Kentaro; Ohno, Masato

    1989-01-01

    Magnetic resonance imaging (MRI) of wallerian degeneration of the corticospinal tract in the brain stem was studied in 25 patients with chronic supratentorial vascular accidents. In the relatively early stages, at least three months after ictus, increased signal intensities in axial T 2 -weighted images - with or without decreased signal intensities in axial T 1 -weighted images - were observed in the brain stem ipsilaterally. In later stages, at least six months after ictus, shrinkage of the brain stem ipsilaterally - with or without decreased signal intensities - was clearly observed in axial T 1 -weighted images. MRI is therefore regarded a sensitive diagnostic modality for evaluating wallerian degeneration in the brain stem. (author)

  12. Semiautomated volumetry of the cerebrum, cerebellum-brain stem, and temporal lobe on brain magnetic resonance images

    International Nuclear Information System (INIS)

    Hayashi, Norio; Matsuura, Yukihiro; Kawahara, Kazuhiro; Tsujii, Hideo; Yamamoto, Tomoyuki; Sanada, Shigeru; Suzuki, Masayuki; Matsui, Osamu

    2008-01-01

    The aim of this study was to develop an automated method of segmenting the cerebrum, cerebellum-brain stem, and temporal lobe simultaneously on magnetic resonance (MR) images. We obtained T1-weighted MR images from 10 normal subjects and 19 patients with brain atrophy. To perform automated volumetry from MR images, we performed the following three steps: segmentation of the brain region; separation between the cerebrum and the cerebellum-brain stem; and segmentation of the temporal lobe. Evaluation was based on the correctly recognized region (CRR) (i.e., the region recognized by both the automated and manual methods). The mean CRRs of the normal and atrophic brains were 98.2% and 97.9% for the cerebrum, 87.9% and 88.5% for the cerebellum-brain stem, and 76.9% and 85.8% for the temporal lobe, respectively. We introduce an automated volumetric method for the cerebrum, cerebellum-brain stem, and temporal lobe on brain MR images. Our method can be applied to not only the normal brain but also the atrophic brain. (author)

  13. Establishment of 9L/F344 rat intracerebral glioma model of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Zong-yu XIAO

    2015-04-01

    Full Text Available Objective To establish the 9L/F344 rat intracerebral glioma model of brain tumor stem cells.  Methods Rat 9L gliosarcoma stem-like cells were cultured in serum-free suspension. The expression of CD133 and nestin were tested by immunohistochemistry. A total of 48 inbredline male F344 rats were randomly divided into 2 groups, and 9L tumor sphere cells and 9L monolayer cells were respectively implanted into the right caudate nucleus of F344 rats in 2 groups. Survival time was observed and determined using the method of Kaplan-Meier survival analysis. Fourteen days after implantation or when the rats were dying, their brains were perfused and sectioned for HE staining, and CD133 and nestin were detected by immunohistochemistry.  Results Rat 9L tumor spheres were formed with suspension culture in serum-free medium. The gliomas formed in both groups were invasive without obvious capsule. More new vessels, bleeding and necrosis could be detected in 9L tumor spheres group. The tumor cells in both groups were positive for CD133 and nestin. There was no significant difference in the expression of CD133 and nestin between 2 groups (P > 0.05, for all. According to the expression of nestin, the tumors formed by 9L tumor sphere cells were more invasive. The median survival time of the rats bearing 9L tumor sphere cells was 15 d (95%CI: 15.219-15.781, and the median survival time of the rats bearing 9L monolayer cells was 21 d (95%CI: 20.395-21.605. There was significant difference between 2 groups (χ2 = 12.800, P = 0.000.  Conclusions 9L/F344 rat intracerebral glioma model of brain tumor stem cells is successfully established, which provides a glioma model for the future research. DOI: 10.3969/j.issn.1672-6731.2015.04.012

  14. Clinical implementation of stereotaxic brain implant optimization

    International Nuclear Information System (INIS)

    Rosenow, U.F.; Wojcicka, J.B.

    1991-01-01

    This optimization method for stereotaxic brain implants is based on seed/strand configurations of the basic type developed for the National Cancer Institute (NCI) atlas of regular brain implants. Irregular target volume shapes are determined from delineation in a stack of contrast enhanced computed tomography scans. The neurosurgeon may then select up to ten directions, or entry points, of surgical approach of which the program finds the optimal one under the criterion of smallest target volume diameter. Target volume cross sections are then reconstructed in 5-mm-spaced planes perpendicular to the implantation direction defined by the entry point and the target volume center. This information is used to define a closed line in an implant cross section along which peripheral seed strands are positioned and which has now an irregular shape. Optimization points are defined opposite peripheral seeds on the target volume surface to which the treatment dose rate is prescribed. Three different optimization algorithms are available: linear least-squares programming, quadratic programming with constraints, and a simplex method. The optimization routine is implemented into a commercial treatment planning system. It generates coordinate and source strength information of the optimized seed configurations for further dose rate distribution calculation with the treatment planning system, and also the coordinate settings for the stereotaxic Brown-Roberts-Wells (BRW) implantation device

  15. The brain stem function in patients with brain bladder

    International Nuclear Information System (INIS)

    Takahashi, Toshihiro

    1990-01-01

    A syndrome of detrusor-sphincter dyssynergia (DSD) is occasionally found in patients with brain bladder. To evaluate the brain stem function in cases of brain bladder, urodynamic study, dynamic CT scan of the brain stem (DCT) and auditory brainstem response (ABR) were performed. The region of interest of DCT aimed at the posterolateral portion of the pons. The results were analysed in contrast with the presense of DSD in urodynamic study. DCT studies were performed in 13 cases with various brain diseases and 5 control cases without neurological diseases. Abnormal patterns of the time-density curve consisted of low peak value, prolongation of filling time and low rapid washout ratio (low clearance ratio) of the contrast medium. Four of 6 cases with DSD showed at least one of the abnormal patterns of the time-density curve bilaterally. In 7 cases without DSD none showed bilateral abnormality of the curve and in 2 of 7 cases only unilateral abnormality was found. ABR was performed in 8 patients with brain diseases. The interpeak latency of the wave I-V (I-V IPL) was considered to be prolonged in 2 cases with DSD compared to that of 4 without DSD. In 2 cases with DSD who had normal DCT findings, measurement of the I-V IPL was impossible due to abnormal pattern of the ABR wave. Above mentioned results suggests the presence of functional disturbance at the posterolateral portion of the pons in cases of brain bladder with DSD. (author)

  16. Are there fetal stem cells in the maternal brain?

    Institute of Scientific and Technical Information of China (English)

    Osman Demirhan; Necmi (C)ekin; Deniz Ta(s)temir; Erdal Tun(c); Ali irfan Güzel; Demet Meral; Bülent Demirbek

    2013-01-01

    Fetal cells can enter maternal blood during pregnancy but whether they can also cross the blood-brain barrier to enter the maternal brain remains poorly understood. Previous results suggest that fetal cells are summoned to repair damage to the mother's brain. If this is confirmed, it would open up new and safer avenues of treatment for brain damage caused by strokes and neural diseases. In this study, we aimed to investigate whether a baby's stem cells can enter the maternal brain during pregnancy. Deceased patients who had at least one male offspring and no history of abortion and blood transfusion were included in this study. DNA was extracted from brain tissue samples of deceased women using standard phenol-chloroform extraction and ethanol precipitation methods. Genomic DNA was screened by quantitative fluorescent-polymerase chain reaction amplification together with short tandem repeat markers specific to the Y chromosome, and 13, 18, 21 and X. Any foreign DNA residues that could be used to interpret the presence of fetal stem cells in the maternal brain were monitored. Results indicated that fetal stem cells can not cross the blood-brain barrier to enter the maternal brain.

  17. Cellular modulation of polymeric device surfaces: promise of adult stem cells for neuroprosthetics

    Directory of Open Access Journals (Sweden)

    Anja eRichter

    2011-10-01

    Full Text Available Minimizing the foreign body response is seen as one critical research strategy for implants especially when designed for immune-privileged organs like the brain. The context of this work is to improve deep brain stimulating devices used in a consistently growing spectrum of psychomotoric and psychiatric diseases mainly in form of stiff electrodes. Based on the compliance match hypothesis of biocompatibility we present another step forward using flexible implant materials covered with brain-mimicking layers. Therefore we covered two types of flexible polyimide films with glandular stem cells derived from pancreatic acini. Using Real Time-PCR and fluorescent immunocytochemistry we analyzed markers representing various cell types of all three germ layers and stemness. The results demonstrate on mRNA and protein level the unchanged differentiation potential of the cells on the polyimides. We additionally developed a fibrinous hydrogel coating to protect them against shear forces upon eventual implantation. By repeating previous analysis and additional metabolism tests for all stages we corroborate the validity of this improvement. Consequently we assume that a stem cell cover may provide a native, fully and actively integrating brain-mimicking interface to the neuropil.

  18. Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke.

    Science.gov (United States)

    Tatebayashi, Kotaro; Tanaka, Yasue; Nakano-Doi, Akiko; Sakuma, Rika; Kamachi, Saeko; Shirakawa, Manabu; Uchida, Kazutaka; Kageyama, Hiroto; Takagi, Toshinori; Yoshimura, Shinichi; Matsuyama, Tomohiro; Nakagomi, Takayuki

    2017-06-01

    Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to understand the traits of iSCs in the poststroke human brain for possible applications in stem cell-based therapies for stroke patients. In this study, we report for the first time that iSCs can be isolated from the poststroke human brain. Putative iSCs were derived from poststroke brain tissue obtained from elderly stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction. Immunohistochemistry showed that these iSCs were localized near blood vessels within poststroke areas containing apoptotic/necrotic neurons and expressed both the stem cell marker nestin and several pericytic markers. Isolated iSCs expressed these same markers and demonstrated high proliferative potential without loss of stemness. Furthermore, isolated iSCs expressed other stem cell markers, such as Sox2, c-myc, and Klf4, and differentiated into multiple cells in vitro, including neurons. These results show that iSCs, which are likely brain pericyte derivatives, are present within the poststroke human brain. This study suggests that iSCs can contribute to neural repair in patients with stroke.

  19. Technical devices for hearing-impaired individuals: cochlear implants and brain stem implants - developments of the last decade.

    Science.gov (United States)

    Müller, Joachim

    2005-01-01

    Over the past two decades, the fascinating possibilities of cochlear implants for congenitally deaf or deafened children and adults developed tremendously and created a rapidly developing interdisciplinary research field.The main advancements of cochlear implantation in the past decade are marked by significant improvement of hearing and speech understanding in CI users. These improvements are attributed to the enhancement of speech coding strategies.The Implantation of more (and increasingly younger) children as well as the possibilities of the restoration of binaural hearing abilities with cochlear implants reflect the high standards reached by this development. Despite this progress, modern cochlear implants do not yet enable normal speech understanding, not even for the best patients. In particular speech understanding in noise remains problematic [1]. Until the mid 1990ies research concentrated on unilateral implantation. Remarkable and effective improvements have been made with bilateral implantation since 1996. Nowadays an increasing numbers of patients enjoy these benefits.

  20. Acute traumatic brain-stem hemorrhage produced by sudden caudal displacement of the brain

    International Nuclear Information System (INIS)

    Mirvis, S.E.; Wolf, A.L.; Thompson, R.K.

    1990-01-01

    This paper determines in an experimental canine study and a clinical review, whether acute caudal displacement of the brain following blunt trauma produces hemorrhage in the rostral anterior midline of the brain stem by tethering the basilar to the fixed carotid arteries. In four dogs, a balloon catheter was suddenly inflated over the frontal lobe; in two, the carotid-basilar vascular connections were severed prior to balloon inflation. ICP was monitored during and after balloon inflation. Hemorrhage was verified by MR imaging and direct inspection of the fixed brain specimens. Admission CT scans demonstrating acute traumatic brain stem hemorrhage (TBH) in human patients were reviewed to determine the site of TBH, predominant site of impact, and neurologic outcome

  1. Cochlear Implant Outcomes and Genetic Mutations in Children with Ear and Brain Anomalies

    Directory of Open Access Journals (Sweden)

    Micol Busi

    2015-01-01

    Full Text Available Background. Specific clinical conditions could compromise cochlear implantation outcomes and drastically reduce the chance of an acceptable development of perceptual and linguistic capabilities. These conditions should certainly include the presence of inner ear malformations or brain abnormalities. The aims of this work were to study the diagnostic value of high resolution computed tomography (HRCT and magnetic resonance imaging (MRI in children with sensorineural hearing loss who were candidates for cochlear implants and to analyse the anatomic abnormalities of the ear and brain in patients who underwent cochlear implantation. We also analysed the effects of ear malformations and brain anomalies on the CI outcomes, speculating on their potential role in the management of language developmental disorders. Methods. The present study is a retrospective observational review of cochlear implant outcomes among hearing-impaired children who presented ear and/or brain anomalies at neuroimaging investigations with MRI and HRCT. Furthermore, genetic results from molecular genetic investigations (GJB2/GJB6 and, additionally, in selected cases, SLC26A4 or mitochondrial-DNA mutations on this study group were herein described. Longitudinal and cross-sectional analysis was conducted using statistical tests. Results. Between January 1, 1996 and April 1, 2012, at the ENT-Audiology Department of the University Hospital of Ferrara, 620 cochlear implantations were performed. There were 426 implanted children at the time of the present study (who were <18 years. Among these, 143 patients (64 females and 79 males presented ear and/or brain anomalies/lesions/malformations at neuroimaging investigations with MRI and HRCT. The age of the main study group (143 implanted children ranged from 9 months and 16 years (average = 4.4; median = 3.0. Conclusions. Good outcomes with cochlear implants are possible in patients who present with inner ear or brain abnormalities

  2. Stem cells to regenerate the newborn brain

    NARCIS (Netherlands)

    van Velthoven, C.T.J.

    2011-01-01

    Perinatal hypoxia-ischemia (HI) is a frequent cause of perinatal morbidity and mortality with limited therapeutic options. In this thesis we investigate whether mesenchymal stem cells (MSC) regenerate the neonatal brain after HI injury. We show that transplantation of MSC after neonatal brain injury

  3. Therapeutic interaction of systemically-administered mesenchymal stem cells with peri-implant mucosa.

    Directory of Open Access Journals (Sweden)

    Ryosuke Kondo

    Full Text Available OBJECTIVES: The objective of this study was to investigate the effect of systemically transplanted mesenchymal stem cells (MSCs on the peri-implant epithelial sealing around dental implants. MATERIALS AND METHODS: MSCs were isolated from bone marrow of donor rats and expanded in culture. After recipient rats received experimental titanium dental implants in the bone sockets after extraction of maxillary right first molars, donor rat MSCs were intravenously transplanted into the recipient rats. RESULTS: The injected MSCs were found in the oral mucosa surrounding the dental implants at 24 hours post-transplantation. MSC transplantation accelerated the formation of the peri-implant epithelium (PIE-mediated mucosa sealing around the implants at an early stage after implantation. Subsequently, enhanced deposition of laminin-332 was found along the PIE-implant interface at 4 weeks after the replacement. We also observed enhanced attachment and proliferation of oral mucous epithelial cells. CONCLUSION: Systemically transplanted MSCs might play a critical role in reinforcing the epithelial sealing around dental implants.

  4. Brain stem hypoplasia associated with Cri-du-Chat syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu [Dept. of Radiology, Inha University Hospital, Inha University School of Medicine, Incheon (Korea, Republic of)

    2013-12-15

    Cri-du-Chat syndrome, also called the 5p-syndrome, is a rare genetic abnormality, and only few cases have been reported on its brain MRI findings. We describe the magnetic resonance imaging findings of a 1-year-old girl with Cri-du-Chat syndrome who showed brain stem hypoplasia, particularly in the pons, with normal cerebellum and diffuse hypoplasia of the cerebral hemispheres. We suggest that Cri-du-Chat syndrome chould be suspected in children with brain stem hypoplasia, particularly for those with high-pitched cries.

  5. Identifying cochlear implant channels with poor electrode-neuron interfaces: electrically evoked auditory brain stem responses measured with the partial tripolar configuration.

    Science.gov (United States)

    Bierer, Julie Arenberg; Faulkner, Kathleen F; Tremblay, Kelly L

    2011-01-01

    The goal of this study was to compare cochlear implant behavioral measures and electrically evoked auditory brain stem responses (EABRs) obtained with a spatially focused electrode configuration. It has been shown previously that channels with high thresholds, when measured with the tripolar configuration, exhibit relatively broad psychophysical tuning curves. The elevated threshold and degraded spatial/spectral selectivity of such channels are consistent with a poor electrode-neuron interface, defined as suboptimal electrode placement or reduced nerve survival. However, the psychophysical methods required to obtain these data are time intensive and may not be practical during a clinical mapping session, especially for young children. Here, we have extended the previous investigation to determine whether a physiological approach could provide a similar assessment of channel functionality. We hypothesized that, in accordance with the perceptual measures, higher EABR thresholds would correlate with steeper EABR amplitude growth functions, reflecting a degraded electrode-neuron interface. Data were collected from six cochlear implant listeners implanted with the HiRes 90k cochlear implant (Advanced Bionics). Single-channel thresholds and most comfortable listening levels were obtained for stimuli that varied in presumed electrical field size by using the partial tripolar configuration, for which a fraction of current (σ) from a center active electrode returns through two neighboring electrodes and the remainder through a distant indifferent electrode. EABRs were obtained in each subject for the two channels having the highest and lowest tripolar (σ = 1 or 0.9) behavioral threshold. Evoked potentials were measured with both the monopolar (σ = 0) and a more focused partial tripolar (σ ≥ 0.50) configuration. Consistent with previous studies, EABR thresholds were highly and positively correlated with behavioral thresholds obtained with both the monopolar and partial

  6. Delayed radiation injury of brain stem after radiotherapy in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Yang Yunli; Liu Yingxin; Xie Dong; Su Danke; Chen Mingzhong

    2002-01-01

    Objective: To study the clinical characteristics, MRI findings, diagnosis, treatment and prognostic factors of patients with radiation induced brain stem injury in nasopharyngeal carcinoma. Methods: From January 1991 to January 2001, 24 patients with radiation injury of brain stem were treated, 14 males and 10 females. The latency ranged from 6 to 38 months, with a median of 18 months. The lesions were located in the pons in 10 patients, mesencephalon + pons in 4, pons + medulla oblongata in 5, medulla oblongata in 2 and mesencephalon + pons + medulla oblongata in 3. MRI findings showed that the injury was chiefly presented as hypointensity foci on T 1 WI and hyperintensity foci on T 2 WI. Results: Eighteen patients were treated with dexamethasone in the early phase, with symptoms relieved in 12 patients but unimproved in 6 patients. Eight 44% patients died within the 8-38 months, leaving 16 patients surviving for 0.5 to 6.0 years. Conclusions: Radiation injury of brain stem has a short latency with severe symptoms, signifying poor prognosis. It is suggested that adequate reduction of irradiation volume and dose at the brain stem should be able to lower the incidence of brain stem injury

  7. Wallerian degeneration of the corticospinal tract in the brain stem; MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, Akira; Onomura, Kentaro; Ohno, Masato (Kyushu Rosai Hospital, Kitakyushu, Fukuoka (Japan))

    1989-04-01

    Magnetic resonance imaging (MRI) of wallerian degeneration of the corticospinal tract in the brain stem was studied in 25 patients with chronic supratentorial vascular accidents. In the relatively early stages, at least three months after ictus, increased signal intensities in axial T{sub 2}-weighted images - with or without decreased signal intensities in axial T{sub 1}-weighted images - were observed in the brain stem ipsilaterally. In later stages, at least six months after ictus, shrinkage of the brain stem ipsilaterally - with or without decreased signal intensities - was clearly observed in axial T{sub 1}-weighted images. MRI is therefore regarded a sensitive diagnostic modality for evaluating wallerian degeneration in the brain stem. (author).

  8. In situ epicatechin-loaded hydrogel implants for local drug delivery ...

    African Journals Online (AJOL)

    induce apoptosis and cell cycle arrest in a wide array of cell lines, and protect ... attenuated ischaemic brain injury and inhibition ..... biodegradable smart implants for tissue regeneration after spinal ... Synthetic hydrogels for controlled stem cell.

  9. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model

    DEFF Research Database (Denmark)

    Jensen, Stine Skov; Meyer, Morten; Petterson, Stine Asferg

    2016-01-01

    AIMS: Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking...... invasion and tumor stemness into account. METHODS: Glioblastoma stem cell-like containing spheroid (GSS) cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains...... of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models. RESULTS: We observed a pronounced invasion into brain slice...

  10. CT findings of traumatic primary brain-stem injury

    International Nuclear Information System (INIS)

    Hosaka, Yasuaki; Hatashita, Shizuo; Bandou, Kuniaki; Ueki, Yasuyuki; Abe, Kouzou; Koga, Nobunori; Sugimura, Jun; Sakakibara, Tokiwa; Takagi, Suguru

    1984-01-01

    A series of 27 consecutive patients with traumatic primary brain stem injuries was studied. They were diagnosed by means of clinical signs, neurological examination, and computerized tomography (CT). The CT findings of the brain-stem lesions were classified into 4 types: Type H, spotty, high-density; Type H and L, high- and low-densities; Type L, low-density; Type I, isodensity. The Glasgow coma scale (GCS), neurological findings on admission, CT findings (findings in the brain stem, obliteration of perimesencephalic cistern (PMC), and other findings), and the Glasgow outcome scale (GOS) were examined. In the 9 cases of Type H, there was a correlation between the GCS and the GOS, and the spotty, high-density lesions were localized mainly in the dorsal and/or ventral midbrain parenchyma, but these lesions did not show focal signs and symptoms. Without an obliteration of the PMC, Type-H patients did not always have a bad outcome. In the 4 cases of Type H and L, the 2 cases of Type L, and the 12 cases of Type I, there was an obliteration of the PMC. All of the these cases had a bad outcome (1 case of moderate disability, 3 cases of severe disability, and 14 cases of death). The mechanism producing a spotty, high-density area was discussed. The weaker impact (than the other types) and individual anatomical differences weresupposed to make for a spotty, high-density are in the brain stem. (author)

  11. Neural stem cells in the ischemic and injured brain: endogenous and transplanted.

    Science.gov (United States)

    Dong, Jing; Liu, Baohua; Song, Lei; Lu, Lei; Xu, Haitao; Gu, Yue

    2012-12-01

    Neural stem cells functions as the pool of new neurons in adult brain, and plays important roles in normal brain function. Additionally, this pool reacts to brain ischemia, hemorrhage, trauma and many kinds of diseases, serving as endogenous repair mechanisms. The present manuscript discussed the responses of adult neurogenesis to brain ischemia and other insults, then the potential of neural stem cell transplantation therapy to treat such brain injury conditions.

  12. Stem Cell Technology for (Epi)genetic Brain Disorders.

    Science.gov (United States)

    Riemens, Renzo J M; Soares, Edilene S; Esteller, Manel; Delgado-Morales, Raul

    2017-01-01

    Despite the enormous efforts of the scientific community over the years, effective therapeutics for many (epi)genetic brain disorders remain unidentified. The common and persistent failures to translate preclinical findings into clinical success are partially attributed to the limited efficiency of current disease models. Although animal and cellular models have substantially improved our knowledge of the pathological processes involved in these disorders, human brain research has generally been hampered by a lack of satisfactory humanized model systems. This, together with our incomplete knowledge of the multifactorial causes in the majority of these disorders, as well as a thorough understanding of associated (epi)genetic alterations, has been impeding progress in gaining more mechanistic insights from translational studies. Over the last years, however, stem cell technology has been offering an alternative approach to study and treat human brain disorders. Owing to this technology, we are now able to obtain a theoretically inexhaustible source of human neural cells and precursors in vitro that offer a platform for disease modeling and the establishment of therapeutic interventions. In addition to the potential to increase our general understanding of how (epi)genetic alterations contribute to the pathology of brain disorders, stem cells and derivatives allow for high-throughput drugs and toxicity testing, and provide a cell source for transplant therapies in regenerative medicine. In the current chapter, we will demonstrate the validity of human stem cell-based models and address the utility of other stem cell-based applications for several human brain disorders with multifactorial and (epi)genetic bases, including Parkinson's disease (PD), Alzheimer's disease (AD), fragile X syndrome (FXS), Angelman syndrome (AS), Prader-Willi syndrome (PWS), and Rett syndrome (RTT).

  13. 192Ir high dose rate (HDR) interstitial brain implant: optimisation

    International Nuclear Information System (INIS)

    Tyagi, Anuj; Singh, Dinesh; Chitra, S.; Gupta, J.P.

    2001-01-01

    The new modality of stepping source dosimetry system (SSDs) illustrates a remarkable improvement in attaining the uniform and homogeneous dose distribution within the target volume. The technique enables the physicist to correct for a certain amount of misplacement or curvature of implant geometry. The short course of brachytherapy provides good palliation in terms of functional improvements with low and acceptable toxicity in high-grade glioma. With continual refinements of the technique, brachytherapy performed by a skilled brachytherapy team offers an opportunity to improve patient survival and quality of life. Since 1997, micro selectron HDR 192 Ir treatments are done including gynecological, oesophageal, breast, surface mould, soft tissue sarcoma (STS) and brain in our hospital. In this paper, procedure of interstitial brain implant in glioma as implant technique, simulation and treatment planning will be discussed

  14. Childhood Brain Stem Glioma Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Childhood brain stem glioma presents as a diffuse intrinsic pontine glioma (DIPG; a fast-growing tumor that is difficult to treat and has a poor prognosis) or a focal glioma (grows more slowly, is easier to treat, and has a better prognosis). Learn about the diagnosis, cellular classification, staging, treatment, and clinical trials for pediatric brain stem glioma in this expert-reviewed summary.

  15. Preparation and biocompatibility study of in situ forming polymer implants in rat brains.

    Science.gov (United States)

    Nasongkla, Norased; Boongird, Atthaporn; Hongeng, Suradej; Manaspon, Chawan; Larbcharoensub, Noppadol

    2012-02-01

    We describe the development of polymer implants that were designed to solidify once injected into rat brains. These implants comprised of glycofurol and copolymers of D: ,L: -lactide (LA), ε-caprolactone and poly(ethylene glycol) (PLECs). Scanning electron microscopy (SEM) and gel permeation chromatography (GPC) showed that the extent of implant degradation was increased with LA: content in copolymers. SEM analysis revealed the formation of porosity on implant surface as the degradation proceeds. PLEC with 19.3% mole of LA: was chosen to inject in rat brains at the volume of 10, 25 and 40 μl. Body weights, hematological and histopathological data of rats treated with implants were evaluated on day 3, 6, 14, 30 and 45 after the injection. Polymer solution at the injection volume of 10 μl were tolerated relatively well compared to those of 25 and 40 μl as confirmed by higher body weight and healing action (fibrosis tissue) 30 days after treatment. The results from this study suggest a possible application as drug delivery systems that can bypass the blood brain barrier.

  16. Mapping the calcitonin receptor in human brain stem

    DEFF Research Database (Denmark)

    Bower, Rebekah L; Eftekhari, Sajedeh; Waldvogel, Henry J

    2016-01-01

    understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract...... receptors (AMY) are a heterodimer formed by the coexpression of CTR with receptor activity-modifying proteins (RAMPs). CTR with RAMP1 responds potently to both amylin and CGRP. The brain stem is a major site of action for circulating amylin and is a rich site of CGRP binding. This study aimed to enhance our...

  17. UV-activated 7-dehydrocholesterol-coated titanium implants promote differentiation of human umbilical cord mesenchymal stem cells into osteoblasts.

    Science.gov (United States)

    Satué, María; Ramis, Joana M; Monjo, Marta

    2016-01-01

    Vitamin D metabolites are essential for bone regeneration and mineral homeostasis. The vitamin D precursor 7-dehydrocholesterol can be used after UV irradiation to locally produce active vitamin D by osteoblastic cells. Furthermore, UV-irradiated 7-dehydrocholesterol is a biocompatible coating for titanium implants with positive effects on osteoblast differentiation. In this study, we examined the impact of titanium implants surfaces coated with UV-irradiated 7-dehydrocholesterol on the osteogenic differentiation of human umbilical cord mesenchymal stem cells. First, the synthesis of cholecalciferol (D3) was achieved through the incubation of the UV-activated 7-dehydrocholesterol coating for 48 h at 23℃. Further, we investigated in vitro the biocompatibility of this coating in human umbilical cord mesenchymal stem cells and its potential to enhance their differentiation towards the osteogenic lineage. Human umbilical cord mesenchymal stem cells cultured onto UV-irradiated 7-dehydrocholesterol-coated titanium implants surfaces, combined with osteogenic supplements, upregulated the gene expression of several osteogenic markers and showed higher alkaline phosphatase activity and calcein blue staining, suggesting increased mineralization. Thus, our results show that the use of UV irradiation on 7-dehydrocholesterol -treated titanium implants surfaces generates a bioactive coating that promotes the osteogenic differentiation of human umbilical cord mesenchymal stem cells, with regenerative potential for improving osseointegration in titanium-based bone anchored implants. © The Author(s) 2015.

  18. Mesenchymal stem cells attenuate blood-brain barrier leakage after cerebral ischemia in mice.

    Science.gov (United States)

    Cheng, Zhuo; Wang, Liping; Qu, Meijie; Liang, Huaibin; Li, Wanlu; Li, Yongfang; Deng, Lidong; Zhang, Zhijun; Yang, Guo-Yuan

    2018-05-03

    Ischemic stroke induced matrixmetallo-proteinase-9 (MMP-9) upregulation, which increased blood-brain barrier permeability. Studies demonstrated that mesenchymal stem cell therapy protected blood-brain barrier disruption from several cerebrovascular diseases. However, the underlying mechanism was largely unknown. We therefore hypothesized that mesenchymal stem cells reduced blood-brain barrier destruction by inhibiting matrixmetallo-proteinase-9 and it was related to intercellular adhesion molecule-1 (ICAM-1). Adult ICR male mice (n = 118) underwent 90-min middle cerebral artery occlusion and received 2 × 10 5 mesenchymal stem cell transplantation. Neurobehavioral outcome, infarct volume, and blood-brain barrier permeability were measured after ischemia. The relationship between myeloperoxidase (MPO) activity and ICAM-1 release was further determined. We found that intracranial injection of mesenchymal stem cells reduced infarct volume and improved behavioral function in experimental stroke models (p mesenchymal stem cell-treated mice compared to the control group following ischemia (p cells and myeloperoxidase activity were decreased in mesenchymal stem cell-treated mice (p mesenchymal stem cell therapy attenuated blood-brain barrier disruption in mice after ischemia. Mesenchymal stem cells attenuated the upward trend of MMP-9 and potentially via downregulating ICAM-1 in endothelial cells. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway may influence MMP-9 expression of neutrophils and resident cells, and ICAM-1 acted as a key factor in the paracrine actions of mesenchymal stem cell.

  19. Discovery of Undescribed Brain Tissue Changes Around Implanted Microelectrode Arrays

    Directory of Open Access Journals (Sweden)

    Himanshi Desai

    2012-01-01

    Full Text Available Brain-implantable microelectrode arrays are devicesdesigned to record or electrically stimulate the activity ofneurons in the brain. These devices hold the potential tohelp treat epilepsy, paralysis, blindness, and deafness, andalso provide researchers with insights into a varietyof neural processes, such as memory formation.While these devices have a very promising future,researchers are discovering that their long-termfunctionality is greatly limited by the brain’s naturalimmune response to foreign objects. To improve thefunctional lifetime of these devices, one solution lies infully characterizing and understanding this tissue response.Roles for microglia and astrocytes in this biologicalresponse have been characterized. However, changesto oligodendrocytes, cells that myelinate axons, remainpoorly understood. These cells provide insulationto the axons, which is required for proper neuralfunctioning. Here we report on the changes that occurwith oligodendrocyte processes in tissue aroundmicroelectrode implants in the brain.Six rats were surgically implanted with microelectrodearrays and allowed to recover for 1, 2, or 4 weeks.Subjects were then sacrificed and the brain tissue wasprocessed using our recently developed method, Device-Capture Histology. Immunohistochemistry and confocalmicroscopy was employed to assess the responsearound the device. Results indicated a decrease inoligodendrocyte density and a loss in typical directionalorientation of oligodendrocyte processes in tissue near thedevice. These results suggest alterations in the underlyingneuronal networks around these devices, which maygreatly impact the current functional utility of thesepromising devices.

  20. Influence of bone marrow-derived mesenchymal stem cells pre-implantation differentiation approach on periodontal regeneration in vivo.

    Science.gov (United States)

    Cai, Xinjie; Yang, Fang; Yan, Xiangzhen; Yang, Wanxun; Yu, Na; Oortgiesen, Daniel A W; Wang, Yining; Jansen, John A; Walboomers, X Frank

    2015-04-01

    The implantation of bone marrow-derived mesenchymal stem cells (MSCs) has previously been shown successful to achieve periodontal regeneration. However, the preferred pre-implantation differentiation strategy (e.g. maintenance of stemness, osteogenic or chondrogenic induction) to obtain optimal periodontal regeneration is still unknown. This in vivo study explored which differentiation approach is most suitable for periodontal regeneration. Mesenchymal stem cells were obtained from Fischer rats and seeded onto poly(lactic-co-glycolic acid)/poly(ɛ-caprolactone) electrospun scaffolds, and then pre-cultured under different in vitro conditions: (i) retention of multilineage differentiation potential; (ii) osteogenic differentiation approach; and (iii) chondrogenic differentiation approach. Subsequently, the cell-scaffold constructs were implanted into experimental periodontal defects of Fischer rats, with empty scaffolds as controls. After 6 weeks of implantation, histomorphometrical analyses were applied to evaluate the regenerated periodontal tissues. The chondrogenic differentiation approach showed regeneration of alveolar bone and ligament tissues. The retention of multilineage differentiation potential supported only ligament regeneration, while the osteogenic differentiation approach boosted alveolar bone regeneration. Chondrogenic differentiation of MSCs before implantation is a useful strategy for regeneration of alveolar bone and periodontal ligament, in the currently used rat model. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Subretinal Implantation of Retinal Pigment Epithelial Cells Derived From Human Embryonic Stem Cells: Improved Survival When Implanted as a Monolayer

    Science.gov (United States)

    Diniz, Bruno; Thomas, Padmaja; Thomas, Biju; Ribeiro, Ramiro; Hu, Yuntao; Brant, Rodrigo; Ahuja, Ashish; Zhu, Danhong; Liu, Laura; Koss, Michael; Maia, Mauricio; Chader, Gerald; Hinton, David R.; Humayun, Mark S.

    2013-01-01

    Purpose. To evaluate cell survival and tumorigenicity of human embryonic stem cell–derived retinal pigment epithelium (hESC-RPE) transplantation in immunocompromised nude rats. Cells were transplanted as a cell suspension (CS) or as a polarized monolayer plated on a parylene membrane (PM). Methods. Sixty-nine rats (38 male, 31 female) were surgically implanted with CS (n = 33) or PM (n = 36). Cohort subsets were killed at 1, 6, and 12 months after surgery. Both ocular tissues and systemic organs (brain, liver, kidneys, spleen, heart, and lungs) were fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned. Every fifth section was stained with hematoxylin and eosin and analyzed histologically. Adjacent sections were processed for immunohistochemical analysis (as needed) using the following antibodies: anti-RPE65 (RPE-specific marker), anti-TRA-1-85 (human cell marker), anti-Ki67 (proliferation marker), anti-CD68 (macrophage), and anti-cytokeratin (epithelial marker). Results. The implanted cells were immunopositive for the RPE65 and TRA-1-85. Cell survival (P = 0.006) and the presence of a monolayer (P < 0.001) of hESC-RPE were significantly higher in eyes that received the PM. Gross morphological and histological analysis of the eye and the systemic organs after the surgery revealed no evidence of tumor or ectopic tissue formation in either group. Conclusions. hESC-RPE can survive for at least 12 months in an immunocompromised animal model. Polarized monolayers of hESC-RPE show improved survival compared to cell suspensions. The lack of teratoma or any ectopic tissue formation in the implanted rats bodes well for similar results with respect to safety in human subjects. PMID:23833067

  2. Long-term implantation of deep brain stimulation electrodes in the pontine micturition centre of the Göttingen minipig.

    Science.gov (United States)

    Jensen, Kristian N; Deding, Dorthe; Sørensen, Jens Christian; Bjarkam, Carsten R

    2009-07-01

    To implant deep brain stimulation (DBS) electrodes in the porcine pontine micturition centre (PMC) in order to establish a large animal model of PMC-DBS. Brain stems from four Göttingen minipigs were sectioned coronally into 40-mum-thick histological sections and stained with Nissl, auto-metallographic myelin stain, tyrosine hydroxylase and corticotrophin-releasing factor immunohistochemistry in order to identify the porcine PMC. DBS electrodes were then stereotaxically implanted on the right side into the PMC in four Göttingen minipigs, and the bladder response to electrical stimulation was evaluated by subsequent cystometry performed immediately after the operation and several weeks later. A paired CRF-dense area homologous to the PMC in other species was encountered in the rostral pontine tegmentum medial to the locus coeruleus and ventral to the floor of the fourth ventricle. Electrical stimulation of the CRF-dense area resulted in an increased detrusor pressure followed by visible voiding in some instances. The pigs were allowed to survive between 14 and 55 days, and electrical stimulation resulting in an increased detrusor pressure was performed on more than one occasion without affecting consciousness or general thriving. None of the pigs developed postoperative infections or died prematurely. DBS electrodes can be implanted for several weeks in the identified CRF-dense area resulting in a useful large animal model for basic research on micturition and the future clinical use of this treatment modality in neurogenic supra-pontine voiding disorders.

  3. Recruitment of host's progenitor cells to sites of human amniotic fluid stem cells implantation.

    Science.gov (United States)

    Mirabella, Teodelinda; Poggi, Alessandro; Scaranari, Monica; Mogni, Massimo; Lituania, Mario; Baldo, Chiara; Cancedda, Ranieri; Gentili, Chiara

    2011-06-01

    The amniotic fluid is a new source of multipotent stem cells with a therapeutic potential for human diseases. Cultured at low cell density, human amniotic fluid stem cells (hAFSCs) were still able to generate colony-forming unit-fibroblast (CFU-F) after 60 doublings, thus confirming their staminal nature. Moreover, after extensive in vitro cell expansion hAFSCs maintained a stable karyotype. The expression of genes, such as SSEA-4, SOX2 and OCT3/4 was confirmed at early and later culture stage. Also, hAFSCs showed bright expression of mesenchymal lineage markers and immunoregulatory properties. hAFSCs, seeded onto hydroxyapatite scaffolds and subcutaneously implanted in nude mice, played a pivotal role in mounting a response resulting in the recruitment of host's progenitor cells forming tissues of mesodermal origin such as fat, muscle, fibrous tissue and immature bone. Implanted hAFSCs migrated from the scaffold to the skin overlying implant site but not to other organs. Given their in vivo: (i) recruitment of host progenitor cells, (ii) homing towards injured sites and (iii) multipotentiality in tissue repair, hAFSCs are a very appealing reserve of stem cells potentially useful for clinical application in regenerative medicine. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Analysis of migration of the Nanos® short-stem hip implant within two years after surgery.

    Science.gov (United States)

    Budde, Stefan; Seehaus, Frank; Schwarze, Michael; Hurschler, Christof; Floerkemeier, Thilo; Windhagen, Henning; Noll, Yvonne; Ettinger, Max; Thorey, Fritz

    2016-08-01

    Short-stem implants provide a bone-preserving alternative in total hip arthroplasty. However, some evidence exists that the smaller implant-bone contact surface may compromise primary stability and impair osseo-integration. The purpose of this study was to analyse the migration characteristics of the Nanos® short stem over two years by means of model-based roentgen stereophotogrammetric analysis (MBRSA). Eighteen patients aged 53.6 ± 7.2 years were included. After being treated with a Nanos implant, 14 patients were followed-up radiologically at three, six, 12 and 24 months by means of MBRSA. Early implant migration was calculated. Clinical data have been assessed in addition. Highest translational migration was observed with a mean value of -0.22 ± 0.39 mm along the proximo-distal axis after three months and highest rotational migration with 0.8 ± 3.2° also around the y-axis after two years. The resulting total migration was 0.46 ± 0.31 mm, with the largest proportion occurring within three months after surgery (0.40 ± 0.34 mm). The Nanos short-stem hip implant shows only a slight initial migration within three months after implantation, followed by secondary stabilisation. These results suggest both good primary stability and osseo-integration, suggesting a low risk of aseptic loosening.

  5. Transcriptional profiling of adult neural stem-like cells from the human brain.

    Directory of Open Access Journals (Sweden)

    Cecilie Jonsgar Sandberg

    Full Text Available There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60. Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate. We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6, foetal human neural stem cells (n = 1 and human brain tissues (n = 12. The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular

  6. Diffusion-weighted magnetic resonance imaging (MRI) in acute brain stem infarction

    International Nuclear Information System (INIS)

    Narisawa, Aya; Shamoto, Hiroshi; Shimizu, Hiroaki; Tominaga, Teiji; Yoshimoto, Takashi

    2001-01-01

    Diffusion-weighted magnetic resonance imaging (DWI) provides one of the earliest demonstrations of ischemic lesions. However some lesions may be missed in the acute stage due to technical limitation of DWI. We therefore conducted the study to clarify the sensitivity of DWI to acute brain stem infarctions. Twenty-eight patients with the final diagnosis of brain stem infarction (midbrain 2, pons 9, medulla oblongata 17) who had been examined by DWI within 24 hours of onset were retrospectively analyzed for how sensitively the initial DWI demonstrated the final ischemic lesion. Only obvious (distinguishable with DWI alone without referring clinical symptoms and other informations) hyperintensity on DWI was regarded to show an ischemic lesion. Sixteen (57.1%) out of 28 patients had brain stem infarctions demonstrated by initial DWI. In the remaining 12 cases, no obvious ischemic lesion was evident on initial DWI. Subsequent MRI studies obtained 127 hours, on average after the onset showed infarction in the medulla oblongate in 11 cases and in the pons in one case. Negative findings of DWI in the acute stage does not exclude possibility of the brain stem infarction, in particularly medulla oblongata infarction. (author)

  7. Implantation of stem cells in the treatment of acute myocardial infarction

    International Nuclear Information System (INIS)

    Obregon Santos, Angel; Wilford de Leon, Mario; Aroche Aportela, Ronald; Isla Garcia, Rosa; Conde Cerdeira, Hector; Vila Garcia, Elena

    2007-01-01

    A lot of investigations demonstrate the possibility of regeneration of the cardiomiocity from stem cells. A longitudinal, prospective, observational study was conducted in patients with acute myocardial infarction in CIMEQ'S hospital since January 2004 up to January 2007 with the purpose to evaluate the security and efficacy of the intracoronary transfer of autologous bone-marrow-cells during acute myocardial infarction. Patients within seven days of the onset of symptoms of a first ST-segment elevation myocardial infarction, and between 18 and 70 years old. The patients are evaluated previous to apply the procedure and 6 months for clinic, electrocardiography, echocardiography, ergometry and coronariography. The drug eluting stent is placed on the culprit lesion and the bone marrow is stimulated with granulocyte colony-stimulating factor (G-CSF). The mononuclear's cells which are obtained have been implanted using the intracoronary way. The implantation by means of the intracoronary way of stem cells, after of stimulation of bone marrow during acute myocardial infarction demonstrated to be an effective and safety procedure

  8. A reliable method for intracranial electrode implantation and chronic electrical stimulation in the mouse brain.

    Science.gov (United States)

    Jeffrey, Melanie; Lang, Min; Gane, Jonathan; Wu, Chiping; Burnham, W McIntyre; Zhang, Liang

    2013-08-06

    Electrical stimulation of brain structures has been widely used in rodent models for kindling or modeling deep brain stimulation used clinically. This requires surgical implantation of intracranial electrodes and subsequent chronic stimulation in individual animals for several weeks. Anchoring screws and dental acrylic have long been used to secure implanted intracranial electrodes in rats. However, such an approach is limited when carried out in mouse models as the thin mouse skull may not be strong enough to accommodate the anchoring screws. We describe here a screw-free, glue-based method for implanting bipolar stimulating electrodes in the mouse brain and validate this method in a mouse model of hippocampal electrical kindling. Male C57 black mice (initial ages of 6-8 months) were used in the present experiments. Bipolar electrodes were implanted bilaterally in the hippocampal CA3 area for electrical stimulation and electroencephalographic recordings. The electrodes were secured onto the skull via glue and dental acrylic but without anchoring screws. A daily stimulation protocol was used to induce electrographic discharges and motor seizures. The locations of implanted electrodes were verified by hippocampal electrographic activities and later histological assessments. Using the glue-based implantation method, we implanted bilateral bipolar electrodes in 25 mice. Electrographic discharges and motor seizures were successfully induced via hippocampal electrical kindling. Importantly, no animal encountered infection in the implanted area or a loss of implanted electrodes after 4-6 months of repetitive stimulation/recording. We suggest that the glue-based, screw-free method is reliable for chronic brain stimulation and high-quality electroencephalographic recordings in mice. The technical aspects described this study may help future studies in mouse models.

  9. Four cases with localized brain-stem lesion on CT scan following closed head injury

    International Nuclear Information System (INIS)

    Saeki, Naokatsu; Odaki, Masaru; Oka, Nobuo; Takase, Manabu; Ono, Junichi.

    1981-01-01

    Cases of primary brain-stem injury following closed head injury, verified by a CT scan, have been increasingly reported. However, most of them have other intracranial lesions in addition to the brain stem, resulting in a poor outcome. The CT scan of 200 cases with severe head injury-Araki's classification of types 3 and 4 - were analysed. Four cases out of them had localized brain-stem lesion without any other significant intracranial injury on a CT scan at the acute stage and had a better outcome than had previously been reported. In this analysis, these 4 cases were studied, and the CT findings, prognosis, and pathogenesis of the localized brain-stem injury were discussed. Follow-up CT of three cases, and taken one month or more later, showed diffuse cortical atrophy. This may indicate the presence of diffuse cerebral injury which could not be seen on CT scans at the acute stage. This atrophic change may also be related with the mechanism of posttraumatic conscious impairment and posttraumatic neurological deficits, such as mental symptoms and impairment of the higher cortical function. Shearing injury is a probable pathogenesis for this diffuse cortical injury. On the other hand, one case did not have any cortical atrophy on a follow-up CT scan. Therefore, this is a case with a localized primary brain-stem injury. Coup injury against the brain stem by a tentorial margin in a case with a small tentorial opening is a possible mechanism producing the localized brain-stem injury. (J.P.N.)

  10. Electrochemical behavior and biological response of Mesenchymal Stem Cells on cp-Ti after N-ions implantation

    Energy Technology Data Exchange (ETDEWEB)

    Rizwan, M.; Ahmad, A. [Department of Metallurgical and Materials Engineering, University of Engineering and Technology, 54890 Lahore (Pakistan); Deen, K.M. [Corrosion Control Research Cell, Department of Metallurgy and Materials Engineering, CEET, University of the Punjab, 54590 Lahore (Pakistan); Haider, W., E-mail: haiderw@utpa.edu [Mechanical Engineering Department, University of Texas Pan American, Edinburg, TX 78539 (United States)

    2014-11-30

    Highlights: • Nitrogen ions of known dosage were implanted on cp-Ti. • Increase in surface roughness with increase in ions dose was confirmed by AFM. • TiN{sub 0.3} and Ti{sub 3}N{sub 2−x} nitride phases were formed and validated by XRD. • The ions implantation reduced the corrosion rate and stabilized the passive film. • Surface roughness greatly affected the morphology and growth of Mesenchymal Stem Cells. - Abstract: Titanium and its alloys are most widely used as implant materials due to their excellent biocompatibility, mechanical properties and chemical stability. In this study Nitrogen ions of known dosage were implanted over cp-Ti by Pelletron accelerator with beam energy of 0.25 MeV.The atomic force microscopy of bare and nitrogen implanted specimens confirmed increase in surface roughness with increase in nitrogen ions concentration. X-ray diffraction patterns of ions implanted surfaces validated the formation of TiN{sub 0.3} and Ti{sub 3}N{sub 2-x}nitride phases. The tendency to form passive film and electrochemical behavior of these surfaces in ringer lactate (RL) solution was evaluated by Potentiodynamic polarization and electrochemical impedance spectroscopy respectively. It is proved that nitrogen ions implantation was beneficial to reduce corrosion rate and stabilizing passive film by increasing charge transfer resistance in RL. It was concluded that morphology and proliferation of Mesenchymal Stem Cells on nitrogen ions implanted surfaces strongly depends on surface roughness and nitride phases.

  11. Distinct spatial distribution of microglia and macrophages following mesenchymal stem cell implantation in mouse brain.

    Science.gov (United States)

    Le Blon, Debbie; Hoornaert, Chloé; Daans, Jasmijn; Santermans, Eva; Hens, Niel; Goossens, Herman; Berneman, Zwi; Ponsaerts, Peter

    2014-09-01

    Although implantation of cellular material in the central nervous system (CNS) is a key direction in CNS regenerative medicine, this approach is currently limited by the occurrence of strong endogenous immune cell responses. In a model of mesenchymal stem cell (MSC) grafting in the CNS of immune-competent mice, we previously described that MSC grafts become highly surrounded and invaded by Iba1(+) myeloid cells (microglia and/or macrophages). Here, following grafting of blue fluorescent protein (BFP)-expressing MSC in the CNS of CX3CR1(+/-) and CX3CR1(-/-) mice, our results indicate: (1) that the observed inflammatory response is independent of the fractalkine signalling axis, and (2) that a significant spatial distribution of Iba1(+) inflammatory cells occurs, in which Iba1(+) CX3CR1(+) myeloid cells mainly surround the MSC graft and Iba1(+) CX3CR1(-) myeloid cells mainly invade the graft at 10 days post transplantation. Although Iba1(+) CX3CR1(+) myeloid cells are considered to be of resident microglial origin, Iba1(+) CX3CR1(-) myeloid cells are most likely of peripheral monocyte/macrophage origin. In order to confirm the latter, we performed MSC-BFP grafting experiments in the CNS of eGFP(+) bone marrow chimeric C57BL/6 mice. Analysis of MSC-BFP grafts in the CNS of these mice confirmed our observation that peripheral monocytes/macrophages invade the MSC graft and that resident microglia surround the MSC graft site. Furthermore, analysis of major histocompatibility complex class II (MHCII) expression revealed that mainly macrophages, but not microglia, express this M1 pro-inflammatory marker in the context of MSC grafting in the CNS. These results again highlight the complexity of cell implantation immunology in the CNS.

  12. Anaesthetic management of a patient with deep brain stimulation implant for radical nephrectomy

    Directory of Open Access Journals (Sweden)

    Monica Khetarpal

    2014-01-01

    Full Text Available A 63-year-old man with severe Parkinson′s disease (PD who had been implanted with deep brain stimulators into both sides underwent radical nephrectomy under general anaesthesia with standard monitoring. Deep brain stimulation (DBS is an alternative and effective treatment option for severe and refractory PD and other illnesses such as essential tremor and intractable epilepsy. Anaesthesia in the patients with implanted neurostimulator requires special consideration because of the interaction between neurostimulator and the diathermy. The diathermy can damage the brain tissue at the site of electrode. There are no standard guidelines for the anaesthetic management of a patient with DBS electrode in situ posted for surgery.

  13. Applications of Mesenchymal Stem Cells in Sinus Lift Augmentation as a Dental Implant Technology

    Directory of Open Access Journals (Sweden)

    Feridoun Parnia

    2018-01-01

    Full Text Available The potential application of stem cell biology in human dentistry is a new and emerging field of research. The objective of the current review was to study the efficiency of mesenchymal stem cells (MSCs in sinus lift augmentation (SLA. A literature review was performed in PubMed Central using MeSH keywords such as sinus lift, MSCs, dental implants, and augmentation. The searches involved full-text papers written in English, published in the past 10 years (2007–2017. The review included in vitro and in vivo studies on the use of MSCs in SLA. Electronic searching provided 45 titles, and among them, 8 papers were chosen as suitable based on the inclusion requirements of this review. The reviewed studies have revealed the potential of MSCs in SLA. According to these papers, stem cell therapy combined with different biomaterials may considerably improve bone regeneration in previous steps of dental implantation and may veritably lead to efficient clinical usages in the recent future. However, the identification of an ideal source of stem cells as well as long-term studies is vital to assess the success rate of this technology. Further clinical trials are also needed to approve the potential of MSCs in SLA.

  14. Sumoylation of hypoxia-inducible factor-1α ameliorates failure of brain stem cardiovascular regulation in experimental brain death.

    Directory of Open Access Journals (Sweden)

    Julie Y H Chan

    2011-03-01

    Full Text Available One aspect of brain death is cardiovascular deregulation because asystole invariably occurs shortly after its diagnosis. A suitable neural substrate for mechanistic delineation of this aspect of brain death resides in the rostral ventrolateral medulla (RVLM. RVLM is the origin of a life-and-death signal that our laboratory detected from blood pressure of comatose patients that disappears before brain death ensues. At the same time, transcriptional upregulation of heme oxygenase-1 in RVLM by hypoxia-inducible factor-1α (HIF-1α plays a pro-life role in experimental brain death, and HIF-1α is subject to sumoylation activated by transient cerebral ischemia. It follows that sumoylation of HIF-1α in RVLM in response to hypoxia may play a modulatory role on brain stem cardiovascular regulation during experimental brain death.A clinically relevant animal model that employed mevinphos as the experimental insult in Sprague-Dawley rat was used. Biochemical changes in RVLM during distinct phenotypes in systemic arterial pressure spectrum that reflect maintained or defunct brain stem cardiovascular regulation were studied. Western blot analysis, EMSA, ELISA, confocal microscopy and immunoprecipitation demonstrated that drastic tissue hypoxia, elevated levels of proteins conjugated by small ubiquitin-related modifier-1 (SUMO-1, Ubc9 (the only known conjugating enzyme for the sumoylation pathway or HIF-1α, augmented sumoylation of HIF-1α, nucleus-bound translocation and enhanced transcriptional activity of HIF-1α in RVLM neurons took place preferentially during the pro-life phase of experimental brain death. Furthermore, loss-of-function manipulations by immunoneutralization of SUMO-1, Ubc9 or HIF-1α in RVLM blunted the upregulated nitric oxide synthase I/protein kinase G signaling cascade, which sustains the brain stem cardiovascular regulatory machinery during the pro-life phase.We conclude that sumoylation of HIF-1α in RVLM ameliorates brain stem

  15. Effects of neuroinflammation on the regenerative capacity of brain stem cells.

    Science.gov (United States)

    Russo, Isabella; Barlati, Sergio; Bosetti, Francesca

    2011-03-01

    In the adult brain, neurogenesis under physiological conditions occurs in the subventricular zone and in the dentate gyrus. Although the exact molecular mechanisms that regulate neural stem cell proliferation and differentiation are largely unknown, several factors have been shown to affect neurogenesis. Decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age-related brain dysfunction. Furthermore, in pathological conditions of the central nervous system associated with neuroinflammation, inflammatory mediators such as cytokines and chemokines can affect the capacity of brain stem cells and alter neurogenesis. In this review, we summarize the state of the art on the effects of neuroinflammation on adult neurogenesis and discuss the use of the lipopolysaccharide-model to study the effects of inflammation and reactive-microglia on brain stem cells and neurogenesis. Furthermore, we discuss the possible causes underlying reduced neurogenesis with normal aging and potential anti-inflammatory, pro-neurogenic interventions aimed at improving memory deficits in normal and pathological aging and in neurodegenerative diseases. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  16. In-vitro chondrogenic potential of synovial stem cells and chondrocytes allocated for autologous chondrocyte implantation

    DEFF Research Database (Denmark)

    Kubosch, Eva Johanna; Heidt, Emanuel; Niemeyer, Philipp

    2017-01-01

    Purpose: The use of passaged chondrocytes is the current standard for autologous chondrocyte implantation (ACI). De-differentiation due to amplification and donor site morbidity are known drawbacks highlighting the need for alternative cell sources. Methods: Via clinically validated flow cytometry...... analysis, we compared the expression of human stem cell and cartilage markers (collagen type 2 (Col2), aggrecan (ACAN), CD44) of chondrocytes (CHDR), passaged chondrocytes for ACI (CellGenix™), bone marrow derived mesenchymal stem cells (BMSC), and synovial derived stem cells (SDSC). Results: Primary...

  17. The response of breast cancer cells to mesenchymal stem cells: a possible role of inflammation by breast implants.

    Science.gov (United States)

    Orciani, Monia; Lazzarini, Raffaella; Scartozzi, Mario; Bolletta, Elisa; Mattioli-Belmonte, Monica; Scalise, Alessandro; Di Benedetto, Giovanni; Di Primio, Roberto

    2013-12-01

    Breast implants are widely used and at times might cause inflammation as a foreign body, followed by fibrous capsule formation around the implant. In cancer, the inflamed stroma is essential for preservation of the tumor. Mesenchymal stem cells can be recruited to sites of inflammation, and their role in cancer development is debated. The authors assessed the effects of inflammation caused by breast implants' effects on tumor. Mesenchymal stem cells were isolated from the fibrous capsules of women who underwent a second operation after 1 year (presenting inflammation) or after 20 years (not presenting inflammation) since initial surgery. After characterization, cells were co-cultured with MCF7, a breast cancer cell line. The expression of genes involved in oncogenesis, proliferation, and epithelial-to-mesenchymal transition was investigated, followed by Western blot analyses. After co-culture with mesenchymal stem cells from the inflamed capsule, MCF7 induced a dose- and time-dependent increase in proliferation. Polymerase chain reaction analyses revealed a dysregulation of genes involved in oncogenesis, proliferation, and epithelial-to-mesenchymal transition. The subsequent evaluation by Western blot did not confirm these results, showing only a modest decrease in the expression of E-cadherin after co-culture with mesenchymal stem cells (both derived from inflamed or control capsules). These data indicate that inflammation caused by breast implants partially affects proliferation of MCF7 but does not influence key mechanisms of tumor development.

  18. Stereotaxic implantation of dispersed cell suspensions into brain. A systematic appraisal of cell placement and survival

    International Nuclear Information System (INIS)

    Plunkett, R.J.; Weber, R.J.; Oldfield, E.H.

    1988-01-01

    The application of several recent advances in cell biology, brain implantation, and cell-mediated tumor immunotherapy requires successful and reproducible placement of viable cell suspensions into brain. Stereotaxic implantation is being used to inject cytotoxic lymphocytes into gliomas and to replace dopaminergic cells in parkinsonian models. Systematic assessment of the factors that influence success in implantation of cell suspensions into solid tissues is needed. A model was developed for investigation of stereotaxic implantation using radiolabeled rat lymphokine-activated killer (LAK) cells. Anesthetized rats received microliter injections of cell suspension into the right caudate nucleus. The injection volume, cell concentration, infusion rate, and needle size were varied systematically. The animals were sacrificed 1 hour after injection; the brain was removed and sectioned, and the radioactivity was counted. Three aliquots of the suspension were injected into counting tubes for control analysis. Recovery of radioactivity was expressed as the percent of mean counts per minute (cpm) in the right frontal lobe/mean cpm in the three control tubes. To assess the viability of implanted cells, the right frontal region was mechanically dissociated in media and centrifuged, and the pellet and supernatant were counted. By using small needles and slow infusion of volumes of 10 microliters or less, 85% to 90% of the radioactivity was recovered in the caudate nucleus. At least half of the implanted cells were viable. Consistent, accurate implantation of dispersed cells into brain over a range of volumes, cell concentrations, infusion rates, and needle sizes was achieved

  19. A prospective dual-energy X-ray absorptiometry study of bone remodeling after implantation of the Nanos short-stemmed prosthesis.

    Science.gov (United States)

    Zeh, Alexander; Pankow, Franziska; Röllinhoff, Marc; Delank, Stefan; Wohlrab, David

    2013-04-01

    The aim of this study was to analyze the bone remodeling around the Nanos stem (Smith & Nephew, Marl, Germany) after primary total hip arthroplasty for coxarthrosis. In 25 patients (15 male, 10 female, mean age 59.9 years) with the diagnosis of coxarthrosis, a DEXA scan was performed immediately after surgery, 97 days (SD 6.1 days) and 368 days (SD 6.2 days) after implantation of a Nanos prosthesis. Plain radiographs were analyzed digitally for radiolucent lines, varus-valgus femoral stem alignment, measurement of stem migration and changes in varus-valgus femoral stem alignment. The position of the center of rotation (COR) and the offset were assessed pre- and postoperatively. Harris Hip Score was used to evaluate the clinical outcome. The DEXA scan showed a significant and relevant increase in BMD (Bone Mineral Density) in Gruen-Zone 6 (12%) and a decrease in Zone 1 (15%), 2 (5%) and 7 (12%), which was interpreted as reflecting a distal load transfer in the metaphysis of the femur. There was no clinically relevant migration or tilting of the Nanos stem. Radiolucent lines were noted in 12 cases, mainly at the polished tip area of the prosthesis; this was not regarded as a sign of impaired osseointegration. There was no significant difference between the position of the COR and the pre- and postoperative offset. The absence of stem migration, angulation, or relevant radiolucent lines is seen as evidence for an unimpaired osseointegration of the Nanos stem approximately 12 months after implantation. It is concluded that the Nanos prosthesis can reduce loss of BMD of the proximal femur composed with conventional stems or other short-stemmed implants.

  20. Toward angiogenesis of implanted bio-artificial liver using scaffolds with type I collagen and adipose tissue-derived stem cells.

    Science.gov (United States)

    Lee, Jae Geun; Bak, Seon Young; Nahm, Ji Hae; Lee, Sang Woo; Min, Seon Ok; Kim, Kyung Sik

    2015-05-01

    Stem cell therapies for liver disease are being studied by many researchers worldwide, but scientific evidence to demonstrate the endocrinologic effects of implanted cells is insufficient, and it is unknown whether implanted cells can function as liver cells. Achieving angiogenesis, arguably the most important characteristic of the liver, is known to be quite difficult, and no practical attempts have been made to achieve this outcome. We carried out this study to observe the possibility of angiogenesis of implanted bio-artificial liver using scaffolds. This study used adipose tissue-derived stem cells that were collected from adult patients with liver diseases with conditions similar to the liver parenchyma. Specifically, microfilaments were used to create an artificial membrane and maintain the structure of an artificial organ. After scratching the stomach surface of severe combined immunocompromised (SCID) mice (n=4), artificial scaffolds with adipose tissue-derived stem cells and type I collagen were implanted. Expression levels of angiogenesis markers including vascular endothelial growth factor (VEGF), CD34, and CD105 were immunohistochemically assessed after 30 days. Grossly, the artificial scaffolds showed adhesion to the stomach and surrounding organs; however, there was no evidence of angiogenesis within the scaffolds; and VEGF, CD34, and CD105 expressions were not detected after 30 days. Although implantation of cells into artificial scaffolds did not facilitate angiogenesis, the artificial scaffolds made with type I collagen helped maintain implanted cells, and surrounding tissue reactions were rare. Our findings indicate that type I collagen artificial scaffolds can be considered as a possible implantable biomaterial.

  1. Finite difference time domain (FDTD) modeling of implanted deep brain stimulation electrodes and brain tissue.

    Science.gov (United States)

    Gabran, S R I; Saad, J H; Salama, M M A; Mansour, R R

    2009-01-01

    This paper demonstrates the electromagnetic modeling and simulation of an implanted Medtronic deep brain stimulation (DBS) electrode using finite difference time domain (FDTD). The model is developed using Empire XCcel and represents the electrode surrounded with brain tissue assuming homogenous and isotropic medium. The model is created to study the parameters influencing the electric field distribution within the tissue in order to provide reference and benchmarking data for DBS and intra-cortical electrode development.

  2. Persistent Inflammation Alters the Function of the Endogenous Brain Stem Cell Compartment

    OpenAIRE

    Pluchino, Stefano; Muzio, Luca; Alfaro-Cervello, Clara; Salani, Giuliana; Porcheri, Cristina; Brambilla, Elena; Cavasinni, Francesca; Bergamaschi, Andrea; Garcia-Verdugo, Jose Manuel; Comi, Giancarlo; Martino, Gianvito; Imitola, Jaime; Deleidi, Michela; Khoury, Samia Joseph

    2008-01-01

    Endogenous neural stem/precursor cells (NPCs) are considered a functional reservoir for promoting tissue homeostasis and repair after injury, therefore regenerative strategies that mobilize these cells have recently been proposed. Despite evidence of increased neurogenesis upon acute inflammatory insults (e.g. ischaemic stroke), the plasticity of the endogenous brain stem cell compartment in chronic CNS inflammatory disorders remains poorly characterized. Here we show that persistent brain in...

  3. Neurogenesis in the brain stem of the rabbit: an autoradiographic study

    International Nuclear Information System (INIS)

    Oblinger, M.M.; Das, G.D.

    1981-01-01

    With the aid of ( 3 H)-thymidine autoradiography, neurogenesis was documented in the nuclear groups of the medulla oblongata, pons, and mid-brain, as well as in the brain stem reticular formation of the rabbit. Following single injections of ( 3 H)-thymidine, counts were taken of intensely labeled neurons within the nuclei of the functional columns related to the cranial nerves, nuclei of several other functional classifications, and nuclei that did not fit into a functional category. In the brain stem as a whole, neurogenesis was found to occur between days 10.0 and 18.5 of gestation: however, the majority of nuclei studied contained intensely neurons only between days 12.0 and 15.0. Only in the pontine nucleus and the tectum were intensely labeled cells observed as late as day 18.5. Directional gradients of histogenesis were often observed within, as well as between, various nuclei. Within the nuclear columns related to the cranial nerves, a clear mediolateral spread of neurogenesis was observable such that nuclei of the motor columns reached a peak in neurogenesis before those in the sensory columns. Likewise, a mediolateral proliferation pattern was seen in the brain stem reticular formation. Other individual directional gradients were discernible; however, in the brain stem as a whole, distinct overall gradients were not observable. In many individual nuclei, gradients in neuron size were observed such that large neurons preferentially arose prior to smaller neurons. Information pertaining to gradients in neurogenesis, as well as to relationships among functionally related nuclei, are discussed

  4. Hermetic electronic packaging of an implantable brain-machine-interface with transcutaneous optical data communication.

    Science.gov (United States)

    Schuettler, Martin; Kohler, Fabian; Ordonez, Juan S; Stieglitz, Thomas

    2012-01-01

    Future brain-computer-interfaces (BCIs) for severely impaired patients are implanted to electrically contact the brain tissue. Avoiding percutaneous cables requires amplifier and telemetry electronics to be implanted too. We developed a hermetic package that protects the electronic circuitry of a BCI from body moisture while permitting infrared communication through the package wall made from alumina ceramic. The ceramic package is casted in medical grade silicone adhesive, for which we identified MED2-4013 as a promising candidate.

  5. Comparison of biological characteristics of mesenchymal stem cells grown on two different titanium implant surfaces

    International Nuclear Information System (INIS)

    Wang Chengyue; Zhao Baohong; Ai Hongjun; Wang Yiwei

    2008-01-01

    This study examined the biological characteristics of mesenchymal stem cells (MSCs) grown on sand-blasted, large-grit, acid-etched (SLA) surface and hydroxyapatite (HA) coating on the SLA (HA/SLA) surface of titanium dental implants. The HA/SLA surfaces of titanium dental implants were formed by the ion beam assisted deposition (IBAD) method. Rabbit bone marrow derived mesenchymal stem cells cultured in vitro were seeded onto the surface of SLA and HA/SLA; the growth states of MSCs on the two samples were observed by a scanning electron microscope; the proliferation index, alkaline phosphatase (ALP) activity, osteocalcin (OCN) content of MSCs and mRNA relative expression level of osteopontin (opn) were compared between two groups. MSCs were found to be easier to adhere to the HA/SLA surface compared to the SLA surface. At the same time, the ALP activity and the OCN content of MSCs grown on the HA/SLA surface were obviously higher, and the relative expression level of opn mRNA was 4.78 times higher than that on the SLA surface. The HA coating formed by the IBAD method on the SLA surface of titanium dental implants significantly improves proliferation and well-differentiated osteoblastic phenotype of MSCs, which indicates a promising method for the surface modification of titanium dental implants

  6. Comparative brain stem lesions on MRI of acute disseminated encephalomyelitis, neuromyelitis optica, and multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Zhengqi Lu

    Full Text Available BACKGROUND: Brain stem lesions are common in patients with acute disseminated encephalomyelitis (ADEM, neuromyelitis optica (NMO, and multiple sclerosis (MS. OBJECTIVES: To investigate comparative brain stem lesions on magnetic resonance imaging (MRI among adult patients with ADEM, NMO, and MS. METHODS: Sixty-five adult patients with ADEM (n = 17, NMO (n = 23, and MS (n = 25 who had brain stem lesions on MRI were enrolled. Morphological features of brain stem lesions among these diseases were assessed. RESULTS: Patients with ADEM had a higher frequency of midbrain lesions than did patients with NMO (94.1% vs. 17.4%, P<0.001 and MS (94.1% vs. 40.0%, P<0.001; patients with NMO had a lower frequency of pons lesions than did patients with MS (34.8% vs. 84.0%, P<0.001 and ADEM (34.8% vs. 70.6%, P = 0.025; and patients with NMO had a higher frequency of medulla oblongata lesions than did patients with ADEM (91.3% vs. 35.3%, P<0.001 and MS (91.3% vs. 36.0%, P<0.001. On the axial section of the brain stem, the majority (82.4% of patients with ADEM showed lesions on the ventral part; the brain stem lesions in patients with NMO were typically located in the dorsal part (91.3%; and lesions in patients with MS were found in both the ventral (44.0% and dorsal (56.0% parts. The lesions in patients with ADEM (100% and NMO (91.3% had poorly defined margins, while lesions of patients with MS (76.0% had well defined margins. Brain stem lesions in patients with ADEM were usually bilateral and symmetrical (82.4%, while lesions in patients with NMO (87.0% and MS (92.0% were asymmetrical or unilateral. CONCLUSIONS: Brain stem lesions showed various morphological features among adult patients with ADEM, NMO, and MS. The different lesion locations may be helpful in distinguishing these diseases.

  7. Aberrant brain-stem morphometry associated with sleep disturbance in drug-naïve subjects with Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Lee JH

    2016-08-01

    Full Text Available Ji Han Lee,1 Won Sang Jung,2 Woo Hee Choi,3 Hyun Kook Lim4 1Washington University in St Louis, St Louis, MO, USA; 2Department of Radiology, 3Department of Nuclear Medicine, 4Department of Psychiatry, Saint Vincent Hospital, College of Medicine, The Catholic University of Korea, Suwon, South Korea Objective: Among patients with Alzheimer’s disease (AD, sleep disturbances are common and serious noncognitive symptoms. Previous studies of AD patients have identified deformations in the brain stem, which may play an important role in the regulation of sleep. The aim of this study was to further investigate the relationship between sleep disturbances and alterations in brain stem morphology in AD.Materials and methods: In 44 patients with AD and 40 healthy elderly controls, sleep disturbances were measured using the Neuropsychiatry Inventory sleep subscale. We employed magnetic resonance imaging-based automated segmentation tools to examine the relationship between sleep disturbances and changes in brain stem morphology.Results: Analyses of the data from AD subjects revealed significant correlations between the Neuropsychiatry Inventory sleep-subscale scores and structural alterations in the left posterior lateral region of the brain stem, as well as normalized brain stem volumes. In addition, significant group differences in posterior brain stem morphology were observed between the AD group and the control group.Conclusion: This study is the first to analyze an association between sleep disturbances and brain stem morphology in AD. In line with previous findings, this study lends support to the possibility that brain stem structural abnormalities might be important neurobiological mechanisms underlying sleep disturbances associated with AD. Further longitudinal research is needed to confirm these findings. Keywords: Alzheimer’s disease, sleep, brain stem, MRI, shape analysis

  8. [Stem Cells in the Brain of Mammals and Human: Fundamental and Applied Aspects].

    Science.gov (United States)

    Aleksandrova, M A; Marey, M V

    2015-01-01

    Brain stem cells represent an extremely intriguing phenomenon. The aim of our review is to present an integrity vision of their role in the brain of mammals and humans, and their clinical perspectives. Over last two decades, investigations of biology of the neural stem cells produced significant changes in general knowledge about the processes of development and functioning of the brain. Researches on the cellular and molecular mechanisms of NSC differentiation and behavior led to new understanding of their involvement in learning and memory. In the regenerative medicine, original therapeutic approaches to neurodegenerative brain diseases have been elaborated due to fundamental achievements in this field. They are based on specific regenerative potential of neural stem cells and progenitor cells, which possess the ability to replace dead cells and express crucially significant biologically active factors that are missing in the pathological brain. For the needs of cell substitution therapy in the neural diseases, adequate methods of maintaining stem cells in culture and their differentiation into different types of neurons and glial cells, have been developed currently. The success of modern cellular technologies has significantly expanded the range of cells used for cell therapy. The near future may bring new perspective and distinct progress in brain cell therapy due to optimizing the cells types most promising for medical needs.

  9. Sapphire implant based neuro-complex for deep-lying brain tumors phototheranostics

    Science.gov (United States)

    Sharova, A. S.; Maklygina, YU S.; Yusubalieva, G. M.; Shikunova, I. A.; Kurlov, V. N.; Loschenov, V. B.

    2018-01-01

    The neuro-complex as a combination of sapphire implant optical port and osteoplastic biomaterial "Collapan" as an Aluminum phthalocyanine nanoform photosensitizer (PS) depot was developed within the framework of this study. The main goals of such neuro-complex are to provide direct access of laser radiation to the brain tissue depth and to transfer PS directly to the pathological tissue location that will allow multiple optical phototheranostics of the deep-lying tumor region without repeated surgical intervention. The developed complex spectral-optical properties research was carried out by photodiagnostics method using the model sample: a brain tissue phantom. The optical transparency of sapphire implant allows obtaining a fluorescent signal with high accuracy, comparable to direct measurement "in contact" with the tissue.

  10. Physics strategies for sparing neural stem cells during whole-brain radiation treatments

    International Nuclear Information System (INIS)

    Kirby, Neil; Chuang, Cynthia; Pouliot, Jean; Hwang, Andrew; Barani, Igor J.

    2011-01-01

    Purpose: Currently, there are no successful long-term treatments or preventive strategies for radiation-induced cognitive impairments, and only a few possibilities have been suggested. One such approach involves reducing the dose to neural stem cell compartments (within and outside of the hippocampus) during whole-brain radiation treatments for brain metastases. This study investigates the fundamental physics issues associated with the sparing of neural stem cells during photon radiotherapy for brain metastases. Methods: Several factors influence the stem cell dose: intracranial scattering, collimator leakage, beam energy, and total number of beams. The relative importance of these factors is investigated through a set of radiation therapy plans, which are all variations of an initial 6 MV intensity-modulated radiation therapy (IMRT) plan designed to simultaneously deliver a whole-brain dose of 30 Gy and maximally reduce stem cell compartment dose. Additionally, an in-house leaf segmentation algorithm was developed that utilizes jaw motion to minimize the collimator leakage. Results: The plans are all normalized such that 50% of the PTV receives 30 Gy. For the initial 6 MV IMRT plan, 50% of the stem cells receive a dose greater than 6.3 Gy. Calculations indicate that 3.6 Gy of this dose originates from intracranial scattering. The jaw-tracking segmentation algorithm, used in conjunction with direct machine parameter optimization, reduces the 50% stem cell dose to 4.3 and 3.7 Gy for 6 and 10 MV treatment beams, respectively. Conclusions: Intracranial scattering alone is responsible for a large dose contribution to the stem cell compartment. It is, therefore, important to minimize other contributing factors, particularly the collimator leakage, to maximally reduce dose to these critical structures. The use of collimator jaw tracking in conjunction with modern collimators can minimize this leakage.

  11. Paraneoplastic brain stem encephalitis in a woman with anti-Ma2 antibody.

    Science.gov (United States)

    Barnett, M; Prosser, J; Sutton, I; Halmagyi, G M; Davies, L; Harper, C; Dalmau, J

    2001-02-01

    A woman developed brain stem encephalopathy in association with serum anti-Ma2 antibodies and left upper lobe lung mass. T2 weighted MRI of the brain showed abnormalities involving the pons, left middle and superior cerebellar peduncles, and bilateral basal ganglia. Immunohistochemical analysis for serum antineuronal antibodies was confounded by the presence of a non-neuronal specific antinuclear antibody. Immunoblot studies showed the presence of anti-Ma2 antibodies. A premortem tissue diagnosis of the lung mass could not be established despite two CT guided needle biopsies, and the patient died as a result of rapid neurological deterioration. The necropsy showed that the lung lesion was an adenocarcinoma which expressed Ma2 immunoreactive protein. Neuropathological findings included prominent perivascular inflammatory infiltrates, glial nodules, and neuronophagia involving the brain stem, basal ganglia, hippocampus and the dentate nucleus of the cerebellum. Ma2 is an autoantigen previously identified in patients with germ cell tumours of the testis and paraneoplastic brain stem and limbic encephalitis. Our patient's clinical and immunopathological findings indicate that this disorder can affect women with lung adenocarcinoma, and that the encephalitic changes predominate in those regions of the brain known to express high concentrations of Ma proteins.

  12. Brain stem and cerebellar atrophy in chronic progressive neuro-Behçet's disease

    International Nuclear Information System (INIS)

    Kanoto, Masafumi; Hosoya, Takaaki; Toyoguchi, Yuuki; Oda, Atsuko

    2013-01-01

    Purpose: Chronic progressive neuro-Behçet's disease (CPNBD) resembles multiple sclerosis (MS) on patient background and image findings, and therefore is difficult to diagnose. The purpose is to identify the characteristic magnetic resonance imaging (MRI) findings of CPNBD and to clarify the differences between the MRI findings of CPNBD and those of MS. Materials and methods: The subjects consist of a CPNBD group (n = 4; 1 male and 3 females; mean age, 51 y.o.), a MS group (n = 19; 3 males and 16 females; mean age, 45 y.o.) and a normal control group (n = 23; 10 males and 13 females; mean age, 45 y.o.). Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were retrospectively evaluated in each subjects. In middle sagittal brain MR images, the prepontine distance was measured as an indirect index of brain stem and cerebellar atrophy and the pontine and mesencephalic distance was measured as a direct index of brain stem atrophy. These indexes were statistically analyzed. Results: Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were seen in all CPNBD cases. Prepontine distance was significantly different between the CPNBD group and the MS group (p < 0.05), and between the CPNBD group and the normal control group (p < 0.001). Pontine and mesencephalic distance were significantly different between the CPNBD group and the MS group (p < 0.001, p < 0.01 respectively), and between the CPNBD group and the normal control group (p < 0.001). Conclusions: Chronic progressive neuro-Behçet's disease should be considered in patients with brain stem and cerebellar atrophy in addition to leukoencephalopathy similar to that seen in multiple sclerosis

  13. HTLV-I associated myelopathy with multiple spotty areas in cerebral white matter and brain stem by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Hara, Yasuo; Takahashi, Mitsuo; Yoshikawa, Hiroo; Yorifuji, Shirou; Tarui, Seiichiro

    1988-01-01

    A 48-year-old woman was admitted with complaints of urinary incontinence and gait disturbance, both of which had progressed slowly without any sign of remission. Family history was not contributory. Neurologically, extreme spasticity was recoginized in the lower limbs. Babinski sign was positive bilaterally. Flower-like atypical lymphocytes were seen in blood. Positive anti-HTLV-I antibody was confirmed in serum and spinal fluid by western blot. She was diagnosed as having HTLV-I associated myelopathy (HAM). CT reveald calcification in bilateral globus pallidus, and MRI revealed multiple spotty areas in cerebral white matter and brain stem, but no spinal cord lesion was detectable. Electrophysiologically, brain stem auditory evoked potential (BAEP) suggested the presence of bilateral brain stem lesions. Neither median nor posterior tibial nerve somatosensory evoked potentials were evoked, a finding suggesting the existence of spinal cord lesion. In this case, the lesion was not confined to spinal cord, it was also observed in brain stem and cerebral white matter. Such distinct lesions in cerebral white matter and brain stem have not been reported in patients with HAM. It is suggested that HTLV-I is probably associated with cerebral white matter and brain stem.

  14. Aqp 9 and Brain Tumour Stem Cells

    Directory of Open Access Journals (Sweden)

    Guri Fossdal

    2012-01-01

    Full Text Available Several studies have implicated the aquaporins (aqp 1, 4, and 9 in the pathogenesis of malignant brain tumours, suggesting that they contribute to motility, invasiveness, and oedema formation and facilitate metabolism in tumour cells under hypoxic conditions. We have studied the expression of aqp1, 4, and 9 in biopsies from glioblastomas, isolated tumour stem cells grown in a tumoursphere assay and analyzed the progenitor and differentiated cells from these cultures. We have compared these to the situation in normal rat brain, its stem cells, and differentiated cells derived thereof. In short, qPCR in tumour tissue showed presence of aqp1, 4, and 9. In the tumour progenitor population, aqp9 was markedly more highly expressed, whilst in tumour-derived differentiated cells, aqp4 was downregulated. However, immunostaining did not reveal increased protein expression of aqp9 in the tumourspheres containing progenitor cells; in contrast, its expression (both mRNA and protein was high in differentiated cultures. We, therefore, propose that aquaporin 9 may have a central role in the tumorigenesis of glioblastoma.

  15. Delayed radiation-induced necrosis of the brain stem

    International Nuclear Information System (INIS)

    Yukawa, Osamu; Kodama, Yasunori; Kyoda, Jun; Yuki, Kiyoshi; Taniguchi, Eiji; Katayama, Shoichi; Hiroi, Tadashi; Uozumi, Toru.

    1993-01-01

    A 46-year-old man had surgery for a mixed glioma of the frontotemporal lobe. Postoperatively he received 50 Gy of irradiation. Sixteen months later he developed left hemiparesis and left facial palsy. MRI revealed lesion brain stem and basal ganglia. Despite chemotherapy and an additional 50 Gy dose, the patient deteriorated. Autopsy revealed a wide spread radiation-induced necrosis in the right cerebral hemisphere, midbrain and pons. In radiation therapy, great care must be taken to protect the normal brain tissue. (author)

  16. Dosimetric response of radioactive bio glass seeds implants on rabbit brain; Resposta radiodosimetrica de implantes de sementes de biovidros radioativos no cerebro de coelhos

    Energy Technology Data Exchange (ETDEWEB)

    Costa, I.T.; Campos, T.P.R., E-mail: itemponi@yahoo.com.br, E-mail: campos@nuclear.ufmg.br [Programa de Pos-Graduacao em Ciencias e Tecnicas Nucleares - Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2007-07-01

    Interstitial implants of radioactive seeds are used as an efficient way of treating brain tumors. Bio glasses is an interesting alternative to the metallic implanted materials, because they can be absorbed by the organism, reducing the possibilities of side effects. The present paper investigates the dosimetry by the implants performed on rabbit's brain on the NRI/UFMG research group. The spatial distribution of the specific ionizing energy deposited per unit of mass generated by Sm-153 seeds were evaluated. A computational model of the brain's region was built using the software SISCODES produced by the research group. The sections of the computer tomography of a rabbit, which was included on the experiment, were digitalized. Those were converted in a three dimensional voxel model, including the tissues, its chemical composition and density. A simulation of the particles transport is performed by the stochastic code MCNP5. The implants consist of 15 ceramic Ca-Si-Sm seeds enriched with Sm-153, with 1.1.6 mm of length and 0.3 mm diameter, implanted on the rabbit's brain. It was predicted on the model three ribbons of 5 seeds each, spaced by 1.1.2 mm, since the ribbons were in a triangular topology whose vertices were spaced by 8 mm. The activities were 120 MBq/seed. The results show isodose regions superposed over the rabbits' model, reproducing the spatial energy deposition on the brain region. The absorbed dose predicted was 3.2 Gy per 15 seed; however it was not enough to tumor control. The authors suggest to increase the number of seeds and activity, reduction of the space to 5-6 mm among ribbons, improving dose with the beta emitting. (author)

  17. Stereotactic technique of RF antenna implantation for brain hyperthermia

    International Nuclear Information System (INIS)

    Takahashi, H.; Uzuka, T.; Grinev, I.; Tanaka, R.

    2005-01-01

    Full text: We have tried 13.56 MHz RF interstitial hyperthermia for the patients with malignant brain tumor. The purpose of this report is to assess the complication risk rate and the achievement yield of stereotactic procedure for RF antenna implantation into the deep-seated brain tumor. One hundred and twenty-five patients underwent 144 stereotactic RF antenna implantation procedures for interstitial hyperthermia for malignant brain tumors at Niigata University, Japan. One hundred and eight patients had malignant gliomas (54 primary, 54 recurrent), 24 had metastatic tumors, 5 had malignant lymphomas, 5 had meningiomas and 2 had miscellaneous tumors. Indication of this trial was the tumor with inoperative deep-seated tumor or elderly patients. RF antennas and catheters for thermistor probes were set into the tumor with stereotactic apparatus under local anesthesia. Postoperative CT scan underwent in order to assess the accuracy of antenna setting and to check the complications. The hyperthermic treatment underwent with a single antenna in 85 patients, 2 antennas in 43 patients, 3 in 2, 4 in 12, 5 in 1 and 6 antennas in 1 patient. Appropriate RF antenna positioning was obtained in 138 of 144 procedures (95.8 %). Six patients incurred complications (4.2 %). Three patients suffered intratumoral hemorrhage. RF antennas were set into the inappropriate position in 2 cases, hyperthermia was not achieved. One patient occurred with liquorrhea. However, six patients (4.2 %) incurred complications, stereotactic RF antenna setting was a safe and reliable technique of the hyperthermic treatment for the patients with malignant brain tumors. (author)

  18. The integral biologically effective dose to predict brain stem toxicity of hypofractionated stereotactic radiotherapy

    International Nuclear Information System (INIS)

    Clark, Brenda G.; Souhami, Luis; Pla, Conrado; Al-Amro, Abdullah S.; Bahary, Jean-Paul; Villemure, Jean-Guy; Caron, Jean-Louis; Olivier, Andre; Podgorsak, Ervin B.

    1998-01-01

    Purpose: The aim of this work was to develop a parameter for use during fractionated stereotactic radiotherapy treatment planning to aid in the determination of the appropriate treatment volume and fractionation regimen that will minimize risk of late damage to normal tissue. Materials and Methods: We have used the linear quadratic model to assess the biologically effective dose at the periphery of stereotactic radiotherapy treatment volumes that impinge on the brain stem. This paper reports a retrospective study of 77 patients with malignant and benign intracranial lesions, treated between 1987 and 1995, with the dynamic rotation technique in 6 fractions over a period of 2 weeks, to a total dose of 42 Gy prescribed at the 90% isodose surface. From differential dose-volume histograms, we evaluated biologically effective dose-volume histograms and obtained an integral biologically-effective dose (IBED) in each case. Results: Of the 77 patients in the study, 36 had target volumes positioned so that the brain stem received more than 1% of the prescribed dose, and 4 of these, all treated for meningioma, developed serious late damage involving the brain stem. Other than type of lesion, the only significant variable was the volume of brain stem exposed. An analysis of the IBEDs received by these 36 patients shows evidence of a threshold value for late damage to the brain stem consistent with similar thresholds that have been determined for external beam radiotherapy. Conclusions: We have introduced a new parameter, the IBED, that may be used to represent the fractional effective dose to structures such as the brain stem that are partially irradiated with stereotactic dose distributions. The IBED is easily calculated prior to treatment and may be used to determine appropriate treatment volumes and fractionation regimens minimizing possible toxicity to normal tissue

  19. Brain tumour stem cells: implications for cancer therapy and regenerative medicine.

    Science.gov (United States)

    Sanchez-Martin, Manuel

    2008-09-01

    The cancer relapse and mortality rate suggest that current therapies do not eradicate all malignant cells. Currently, it is accepted that tumorigenesis and organogenesis are similar in many respects, as for example, homeostasis is governed by a distinct sub-population of stem cells in both situations. There is increasing evidence that many types of cancer contain their own stem cells: cancer stem cells (CSC), which are characterized by their self-renewing capacity and differentiation ability. The investigation of solid tumour stem cells has gained momentum particularly in the area of brain tumours. Gliomas are the most common type of primary brain tumours. Nearly two-thirds of gliomas are highly malignant lesions with fast progression and unfortunate prognosis. Despite recent advances, two-year survival for glioblastoma (GBM) with optimal therapy is less than 30%. Even among patients with low-grade gliomas that confer a relatively good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells endowed with features of primitive neural progenitor cells and a tumour-initiating function. In general, this fraction is characterized for forming neurospheres, being endowed with drug resistance properties and often, we can isolate some of them using sorting methods with specific antibodies. The molecular characterization of these stem populations will be critical to developing an effective therapy for these tumours with very dismal prognosis. To achieve this aim, the development of a mouse model which recapitulates the nature of these tumours is essential. This review will focus on glioma stem cell knowledge and discuss future implications in brain cancer therapy and regenerative medicine.

  20. Olivary degeneration after cerebellar or brain stem haemorrhage: MRI

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, A. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan) Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Hasuo, K. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Uchida, K. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Matsumoto, S. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Tsukamoto, Y. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Ohno, M. (Dept. of Radiology, Kyushu Rosai Hospital, Kitakyushu (Japan)); Masuda, K. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan))

    1993-05-01

    Magnetic resonance (MR) images of seven patients with olivary degeneration caused by cerebellar or brain stem haemorrhages were reviewed. In four patients with cerebellar haemorrhage, old haematomas were identified as being located in the dentate nucleus; the contralateral inferior olivary nuclei were hyperintense on proton-density- and T2-weighted images. In two patients with pontine haemorrhages, the old haematomas were in the tegmentum and the ipsilateral inferior olivary nuclei, which were hyperintense. In one case of midbrain haemorrhage, the inferior olivary nuclei were hyperintense bilaterally. The briefest interval from the ictus to MRI was 2 months. Hypertrophic olivary nuclei were observed only at least 4 months after the ictus. Olivary degeneration after cerebellar or brain stem haemorrhage should not be confused with ischaemic, neoplastic, or other primary pathological conditions of the medulla. (orig.)

  1. Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development

    Directory of Open Access Journals (Sweden)

    Bello Bruno C

    2008-02-01

    Full Text Available Abstract Background In the mammalian brain, neural stem cells divide asymmetrically and often amplify the number of progeny they generate via symmetrically dividing intermediate progenitors. Here we investigate whether specific neural stem cell-like neuroblasts in the brain of Drosophila might also amplify neuronal proliferation by generating symmetrically dividing intermediate progenitors. Results Cell lineage-tracing and genetic marker analysis show that remarkably large neuroblast lineages exist in the dorsomedial larval brain of Drosophila. These lineages are generated by brain neuroblasts that divide asymmetrically to self renew but, unlike other brain neuroblasts, do not segregate the differentiating cell fate determinant Prospero to their smaller daughter cells. These daughter cells continue to express neuroblast-specific molecular markers and divide repeatedly to produce neural progeny, demonstrating that they are proliferating intermediate progenitors. The proliferative divisions of these intermediate progenitors have novel cellular and molecular features; they are morphologically symmetrical, but molecularly asymmetrical in that key differentiating cell fate determinants are segregated into only one of the two daughter cells. Conclusion Our findings provide cellular and molecular evidence for a new mode of neurogenesis in the larval brain of Drosophila that involves the amplification of neuroblast proliferation through intermediate progenitors. This type of neurogenesis bears remarkable similarities to neurogenesis in the mammalian brain, where neural stem cells as primary progenitors amplify the number of progeny they generate through generation of secondary progenitors. This suggests that key aspects of neural stem cell biology might be conserved in brain development of insects and mammals.

  2. The modulation of stem cell behaviors by functionalized nanoceramic coatings on Ti-based implants

    Directory of Open Access Journals (Sweden)

    Xiangmei Liu

    2016-09-01

    Full Text Available Nanoceramic coating on the surface of Ti-based metallic implants is a clinical potential option in orthopedic surgery. Stem cells have been found to have osteogenic capabilities. It is necessary to study the influences of functionalized nanoceramic coatings on the differentiation and proliferation of stem cells in vitro or in vivo. In this paper, we summarized the recent advance on the modulation of stem cells behaviors through controlling the properties of nanoceramic coatings, including surface chemistry, surface roughness and microporosity. In addition, mechanotransduction pathways have also been discussed to reveal the interaction mechanisms between the stem cells and ceramic coatings on Ti-based metals. In the final part, the osteoinduction and osteoconduction of ceramic coating have been also presented when it was used as carrier of BMPs in new bone formation.

  3. MRI of the brain stem using fluid attenuated inversion recivery pulse sequences

    International Nuclear Information System (INIS)

    De Coene, B.; Hajnal, J.V.; Pennock, J.M.; Bydder, G.M.

    1993-01-01

    Heavily T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences with inversion times of 2000-2500 ms and echo times of 130-200 ms were used to image the brain stem of a normal adult and five patients. These sequences produce high signal from many white matter tracts and display high lesion contrast. The corticospinal and parietopontine tracts, lateral and medial lemnisci, superior and inferior cerebellar peduncles, medial longitudinal fasciculi, thalamo-olivary tracts the cuneate and gracile fasiculi gave high signal and were directly visualised. The oculomotor and trigeminal nerves were demonstrated within the brain stem. Lesions not seen with conventional T2-weighted spin echo sequences were seen with high contrast in patients with infarction, multiple sclerosis, sarcoidosis, chunt obstruction and metastatic tumour. The anatomical detail and high lesion contrast given by the FLAIR pulse sequence appear likely to be of value in diagnosis of disease in the brain stem. (orig.)

  4. Influence of prosthesis design and implantation technique on implant stresses after cementless revision THR

    Directory of Open Access Journals (Sweden)

    Duda Georg N

    2011-05-01

    Full Text Available Abstract Background Femoral offset influences the forces at the hip and the implant stresses after revision THR. For extended bone defects, these forces may cause considerable bending moments within the implant, possibly leading to implant failure. This study investigates the influences of femoral anteversion and offset on stresses in the Wagner SL revision stem implant under varying extents of bone defect conditions. Methods Wagner SL revision stems with standard (34 mm and increased offset (44 mm were virtually implanted in a model femur with bone defects of variable extent (Paprosky I to IIIb. Variations in surgical technique were simulated by implanting the stems each at 4° or 14° of anteversion. Muscle and joint contact forces were applied to the reconstruction and implant stresses were determined using finite element analyses. Results Whilst increasing the implant's offset by 10 mm led to increased implant stresses (16.7% in peak tensile stresses, altering anteversion played a lesser role (5%. Generally, larger stresses were observed with reduced bone support: implant stresses increased by as much as 59% for a type IIIb defect. With increased offset, the maximum tensile stress was 225 MPa. Conclusion Although increased stresses were observed within the stem with larger offset and increased anteversion, these findings indicate that restoration of offset, key to restoring joint function, is unlikely to result in excessive implant stresses under routine activities if appropriate fixation can be achieved.

  5. Patient-derived stem cells: pathways to drug discovery for brain diseases

    Directory of Open Access Journals (Sweden)

    Alan eMackay-Sim

    2013-03-01

    Full Text Available The concept of drug discovery through stem cell biology is based on technological developments whose genesis is now coincident. The first is automated cell microscopy with concurrent advances in image acquisition and analysis, known as high content screening (HCS. The second is patient-derived stem cells for modelling the cell biology of brain diseases. HCS has developed from the requirements of the pharmaceutical industry for high throughput assays to screen thousands of chemical compounds in the search for new drugs. HCS combines new fluorescent probes with automated microscopy and computational power to quantify the effects of compounds on cell functions. Stem cell biology has advanced greatly since the discovery of genetic reprogramming of somatic cells into induced pluripotent stem cells (iPSCs. There is now a rush of papers describing their generation from patients with various diseases of the nervous system. Although the majority of these have been genetic diseases, iPSCs have been generated from patients with complex diseases (schizophrenia and sporadic Parkinson’s disease. Some genetic diseases are also modelled in embryonic stem cells generated from blastocysts rejected during in vitro fertilisation. Neural stem cells have been isolated from post-mortem brain of Alzheimer’s patients and neural stem cells generated from biopsies of the olfactory organ of patients is another approach. These olfactory neurosphere-derived cells demonstrate robust disease-specific phenotypes in patients with schizophrenia and Parkinson’s disease. High content screening is already in use to find small molecules for the generation and differentiation of embryonic stem cells and induced pluripotent stem cells. The challenges for using stem cells for drug discovery are to develop robust stem cell culture methods that meet the rigorous requirements for repeatable, consistent quantities of defined cell types at the industrial scale necessary for high

  6. Novel Cranial Implants of Yttria-Stabilized Zirconia as Acoustic Windows for Ultrasonic Brain Therapy.

    Science.gov (United States)

    Gutierrez, Mario I; Penilla, Elias H; Leija, Lorenzo; Vera, Arturo; Garay, Javier E; Aguilar, Guillermo

    2017-11-01

    Therapeutic ultrasound can induce changes in tissues by means of thermal and nonthermal effects. It is proposed for treatment of some brain pathologies such as Alzheimer's, Parkinson's, Huntington's diseases, and cancer. However, cranium highly absorbs ultrasound reducing transmission efficiency. There are clinical applications of transcranial focused ultrasound and implantable ultrasound transducers proposed to address this problem. In this paper, biocompatible materials are proposed for replacing part of the cranium (cranial implants) based on low porosity polycrystalline 8 mol% yttria-stabilized-zirconia (8YSZ) ceramics as acoustic windows for brain therapy. In order to assess the viability of 8YSZ implants to effectively transmit ultrasound, various 8YSZ ceramics with different porosity are tested; their acoustic properties are measured; and the results are validated using finite element models simulating wave propagation to brain tissue through 8YSZ windows. The ultrasound attenuation is found to be linearly dependent on ceramics' porosity. Results for the nearly pore-free case indicate that 8YSZ is highly effective in transmitting ultrasound, with overall maximum transmission efficiency of ≈81%, compared to near total absorption of cranial bone. These results suggest that 8YSZ polycrystals could be suitable acoustic windows for ultrasound brain therapy at 1 MHz. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Electrochemical behavior and biological response of Mesenchymal Stem Cells on cp-Ti after N-ions implantation

    Science.gov (United States)

    Rizwan, M.; Ahmad, A.; Deen, K. M.; Haider, W.

    2014-11-01

    Titanium and its alloys are most widely used as implant materials due to their excellent biocompatibility, mechanical properties and chemical stability. In this study Nitrogen ions of known dosage were implanted over cp-Ti by Pelletron accelerator with beam energy of 0.25 MeV.The atomic force microscopy of bare and nitrogen implanted specimens confirmed increase in surface roughness with increase in nitrogen ions concentration. X-ray diffraction patterns of ions implanted surfaces validated the formation of TiN0.3 and Ti3N2-xnitride phases. The tendency to form passive film and electrochemical behavior of these surfaces in ringer lactate (RL) solution was evaluated by Potentiodynamic polarization and electrochemical impedance spectroscopy respectively. It is proved that nitrogen ions implantation was beneficial to reduce corrosion rate and stabilizing passive film by increasing charge transfer resistance in RL. It was concluded that morphology and proliferation of Mesenchymal Stem Cells on nitrogen ions implanted surfaces strongly depends on surface roughness and nitride phases.

  8. Imaging of human glioblastoma cells and their interactions with mesenchymal stem cells in the zebrafish (Danio rerio) embryonic brain

    International Nuclear Information System (INIS)

    Vittori, Milos; Breznik, Barbara; Gredar, Tajda; Hrovat, Katja; Bizjak Mali, Lilijana; Lah, Tamara T

    2016-01-01

    An attractive approach in the study of human cancers is the use of transparent zebrafish (Danio rerio) embryos, which enable the visualization of cancer progression in a living animal. We implanted mixtures of fluorescently labeled glioblastoma (GBM) cells and bonemarrow-derived mesenchymal stem cells (MSCs) into zebrafish embryos to study the cellular pathways of their invasion and the interactions between these cells in vivo. By developing and applying a carbocyanine-dye-compatible clearing protocol for observation of cells in deep tissues, we showed that U87 and U373 GBM cells rapidly aggregated into tumor masses in the ventricles and midbrain hemispheres of the zebrafish embryo brain, and invaded the central nervous system, often using the ventricular system and the central canal of the spinal cord. However, the GBM cells did not leave the central nervous system. With co-injection of differentially labeled cultured GBM cells and MSCs, the implanted cells formed mixed tumor masses in the brain. We observed tight associations between GBM cells and MSCs, and possible cell-fusion events. GBM cells and MSCs used similar invasion routes in the central nervous system. This simple model can be used to study the molecular pathways of cellular processes in GBM cell invasion, and their interactions with various types of stromal cells in double or triple cell co-cultures, to design anti-GBM cell therapies that use MSCs as vectors

  9. Characterization of TLX expression in neural stem cells and progenitor cells in adult brains.

    Science.gov (United States)

    Li, Shengxiu; Sun, Guoqiang; Murai, Kiyohito; Ye, Peng; Shi, Yanhong

    2012-01-01

    TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ) of adult mouse brains. Then, using a double thymidine analog labeling approach, we showed that almost all of the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX-positive cells in the SVZ represented the thymidine analog-negative, relatively quiescent neural stem cell population. Using cell type markers and short-term BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly dividing type C cells. Furthermore, loss of TLX expression dramatically reduced BrdU label-retaining neural stem cells and the actively dividing neural progenitor cells in the SVZ, but substantially increased GFAP staining and extended GFAP processes. These results suggest that TLX is essential to maintain the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the SVZ lose neural stem cell property upon loss of TLX expression. Understanding the cellular distribution of TLX and its function in specific cell types may provide insights into the development of therapeutic tools for neurodegenerative diseases by targeting TLX in neural stem/progenitors cells.

  10. Neuroengineering tools/applications for bidirectional interfaces, brain computer interfaces, and neuroprosthetic implants - a review of recent progress

    Directory of Open Access Journals (Sweden)

    Ryan M Rothschild

    2010-10-01

    Full Text Available The main focus of this review is to provide a holistic amalgamated overview of the most recent human in vivo techniques for implementing brain-computer interfaces (BCIs, bidirectional interfaces and neuroprosthetics. Neuroengineering is providing new methods for tackling current difficulties; however neuroprosthetics have been studied for decades. Recent progresses are permitting the design of better systems with higher accuracies, repeatability and system robustness. Bidirectional interfaces integrate recording and the relaying of information from and to the brain for the development of BCIs. The concepts of non-invasive and invasive recording of brain activity are introduced. This includes classical and innovative techniques like electroencephalography (EEG and near-infrared spectroscopy (NIRS. Then the problem of gliosis and solutions for (semi- permanent implant biocompatibility such as innovative implant coatings, materials and shapes are discussed. Implant power and the transmission of their data through implanted pulse generators (IPGs and wireless telemetry are taken into account. How sensation can be relayed back to the brain to increase integration of the neuroengineered systems with the body by methods such as micro-stimulation and transcranial magnetic stimulation (TMS are then addressed. The neuroprosthetic section discusses some of the various types and how they operate. Visual prosthetics are discussed and the three types, dependant on implant location, are examined. Auditory prosthetics, being cochlear or cortical, are then addressed. Replacement hand and limb prosthetics are then considered. These are followed by sections concentrating on the control of wheelchairs, computers and robotics directly from brain activity as recorded by non-invasive and invasive techniques.

  11. Infrequent lesions involving the brain stem: assessment with magnetic resonance

    International Nuclear Information System (INIS)

    Gonzalez, Alejandro P.; Salvatico, Rosana; Romero, Carlos; Lambre, Hector; Trejo, Mariano; Meli, Francisco

    2005-01-01

    Purpose: Report five non frequent cases that involve the brain stem studied with MRI. Material and methods: 115 patients were evaluated retrospectively between January 2002 and March 2004. Five non frequent cases were selected. Their ages were between 3 and 75 years, and all of them were male. A 1.5 magnet was used. The diagnosis was made with the clinical evolution, blood and CSF analysis and in one case by biopsy. Results: The mentioned cases were posterior reversible leucoencephalopathy, rhombencephalitis due to listeria monocytogenes, brain stem infiltrating glioma, Leigh syndrome and pontine myelinolysis. Conclusions: We think that the reported cases have to be considered among the different diagnosis of the brainstem pathology, in spite of their non frequent presentation. (author)

  12. Basal ganglia germinoma in children with associated ipsilateral cerebral and brain stem hemiatrophy

    Energy Technology Data Exchange (ETDEWEB)

    Ozelame, Rodrigo V.; Shroff, Manohar; Wood, Bradley; Bouffet, Eric; Bartels, Ute; Drake, James M.; Hawkins, Cynthia; Blaser, Susan [Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, Ontario (Canada)

    2006-04-15

    Germinoma is the most common and least-malignant intracranial germ cell tumor, usually found in the midline. Germinoma that arises in the basal ganglia, called ectopic germinoma, is a rare and well-documented entity representing 5% to 10% of all intracranial germinomas. The association of cerebral and/or brain stem atrophy with basal ganglia germinoma on CT and MRI is found in 33% of the cases. To review the literature and describe the CT and MRI findings of basal ganglia germinoma in children, known as ectopic germinoma, with associated ipsilateral cerebral and brain stem hemiatrophy. Three brain CT and six brain MRI studies performed in four children at two institutions were retrospectively reviewed. All patients were male (case 1, 14 years; case 2, 13 years; case 3, 9 years; case 4, 13 years), with pathologically proved germinoma arising in the basal ganglia, and associated ipsilateral cerebral and/or brain stem hemiatrophy on the first imaging study. It is important to note that three of these children presented with cognitive decline, psychosis and slowly progressive hemiparesis as their indication for imaging. Imaging results on initial scans were varied. In all patients, the initial study showed ipsilateral cerebral and/or brain stem hemiatrophy, representing Wallerian degeneration. All patients who underwent CT imaging presented with a hyperdense or calcified lesion in the basal ganglia on unenhanced scans. Only one of these lesions had a mass effect on the surrounding structures. In one of these patients a large, complex, heterogeneous mass appeared 15 months later. Initial MR showed focal or diffusely increased T2 signal in two cases and heterogeneous signal in the other two. (orig.)

  13. Basal ganglia germinoma in children with associated ipsilateral cerebral and brain stem hemiatrophy

    International Nuclear Information System (INIS)

    Ozelame, Rodrigo V.; Shroff, Manohar; Wood, Bradley; Bouffet, Eric; Bartels, Ute; Drake, James M.; Hawkins, Cynthia; Blaser, Susan

    2006-01-01

    Germinoma is the most common and least-malignant intracranial germ cell tumor, usually found in the midline. Germinoma that arises in the basal ganglia, called ectopic germinoma, is a rare and well-documented entity representing 5% to 10% of all intracranial germinomas. The association of cerebral and/or brain stem atrophy with basal ganglia germinoma on CT and MRI is found in 33% of the cases. To review the literature and describe the CT and MRI findings of basal ganglia germinoma in children, known as ectopic germinoma, with associated ipsilateral cerebral and brain stem hemiatrophy. Three brain CT and six brain MRI studies performed in four children at two institutions were retrospectively reviewed. All patients were male (case 1, 14 years; case 2, 13 years; case 3, 9 years; case 4, 13 years), with pathologically proved germinoma arising in the basal ganglia, and associated ipsilateral cerebral and/or brain stem hemiatrophy on the first imaging study. It is important to note that three of these children presented with cognitive decline, psychosis and slowly progressive hemiparesis as their indication for imaging. Imaging results on initial scans were varied. In all patients, the initial study showed ipsilateral cerebral and/or brain stem hemiatrophy, representing Wallerian degeneration. All patients who underwent CT imaging presented with a hyperdense or calcified lesion in the basal ganglia on unenhanced scans. Only one of these lesions had a mass effect on the surrounding structures. In one of these patients a large, complex, heterogeneous mass appeared 15 months later. Initial MR showed focal or diffusely increased T2 signal in two cases and heterogeneous signal in the other two. (orig.)

  14. Radiotherapy for pediatric brain stem tumors

    International Nuclear Information System (INIS)

    Shcherbenko, O.I.; Parkhomenko, R.A.; Govorina, E.V.; Zelinskaya, N.I.; Ardatova, G.V.; Nechaeva, V.N.

    2000-01-01

    The immediate and short-term results of gamma therapy of brain stem tumors in 24 children were evaluated. All the patients were able to sustain treatment due to adjuvant support with dehydrating and hormonal drugs, and beneficial clinical effect was recorded in 80%. However, magnetic resonance tomography showed no decrease in tumor size. Tumor growth relapsed 3-8 months after radiotherapy. Although total dose ranged 60-72 Gy in 19 patients, there was no clinical evidence of radiation injury [ru

  15. Fully Implanted Brain-Computer Interface in a Locked-In Patient with ALS.

    Science.gov (United States)

    Vansteensel, Mariska J; Pels, Elmar G M; Bleichner, Martin G; Branco, Mariana P; Denison, Timothy; Freudenburg, Zachary V; Gosselaar, Peter; Leinders, Sacha; Ottens, Thomas H; Van Den Boom, Max A; Van Rijen, Peter C; Aarnoutse, Erik J; Ramsey, Nick F

    2016-11-24

    Options for people with severe paralysis who have lost the ability to communicate orally are limited. We describe a method for communication in a patient with late-stage amyotrophic lateral sclerosis (ALS), involving a fully implanted brain-computer interface that consists of subdural electrodes placed over the motor cortex and a transmitter placed subcutaneously in the left side of the thorax. By attempting to move the hand on the side opposite the implanted electrodes, the patient accurately and independently controlled a computer typing program 28 weeks after electrode placement, at the equivalent of two letters per minute. The brain-computer interface offered autonomous communication that supplemented and at times supplanted the patient's eye-tracking device. (Funded by the Government of the Netherlands and the European Union; ClinicalTrials.gov number, NCT02224469 .).

  16. A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration

    Directory of Open Access Journals (Sweden)

    Eap S

    2015-02-01

    Full Text Available Sandy Eap,1,2,* Laetitia Keller,1–3,* Jessica Schiavi,1,2 Olivier Huck,1,2 Leandro Jacomine,4 Florence Fioretti,1,2 Christian Gauthier,4 Victor Sebastian,1,3,5 Pascale Schwinté,1,2 Nadia Benkirane-Jessel1,21INSERM, UMR 1109, Osteoarticular and Dental Regenerative Nanomedicine Laboratory, FMTS, Faculté de Médecine, Strasbourg, France; 2Faculté de Chirurgie Dentaire, Université de Strasbourg, Strasbourg, France; 3Department of Chemical Engineering, Aragon Nanoscience Institute, University of Zaragoza, Zaragoza, Spain; 4CNRS (National Center for Scientific Research, ICS (Charles Sadron Institute, Strasbourg, France; 5Networking Research Center of Bioengineering, Biomaterials and Nanomedicine, Zaragoza, Spain*These authors contributed equally to this workAbstract: New-generation implants focus on robust, durable, and rapid tissue regeneration to shorten recovery times and decrease risks of postoperative complications for patients. Herein, we describe a new-generation thick nanofibrous implant functionalized with active containers of growth factors and stem cells for regenerative nanomedicine. A thick electrospun poly(ε-caprolactone nanofibrous implant (from 700 µm to 1 cm thick was functionalized with chitosan and bone morphogenetic protein BMP-7 as growth factor using layer-by-layer technology, producing fish scale-like chitosan/BMP-7 nanoreservoirs. This extracellular matrix-mimicking scaffold enabled in vitro colonization and bone regeneration by human primary osteoblasts, as shown by expression of osteocalcin, osteopontin, and bone sialoprotein (BSPII, 21 days after seeding. In vivo implantation in mouse calvaria defects showed significantly more newly mineralized extracellular matrix in the functionalized implant compared to a bare scaffold after 30 days’ implantation, as shown by histological scanning electron microscopy/energy dispersive X-ray microscopy study and calcein injection. We have as well bifunctionalized our BMP-7

  17. Nuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain.

    Science.gov (United States)

    Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

    2008-01-01

    TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain.

  18. Electromagnetic interference of GSM mobile phones with the implantable deep brain stimulator, ITREL-III

    Directory of Open Access Journals (Sweden)

    Alesch François

    2003-05-01

    Full Text Available Abstract Background The purpose was to investigate mobile phone interference with implantable deep brain stimulators by means of 10 different 900 Mega Hertz (MHz and 10 different 1800 MHz GSM (Global System for Mobile Communications mobile phones. Methods All tests were performed in vitro using a phantom especially developed for testing with deep brain stimulators. The phantom was filled with liquid phantom materials simulating brain and muscle tissue. All examinations were carried out inside an anechoic chamber on two implants of the same type of deep brain stimulator: ITREL-III from Medtronic Inc., USA. Results Despite a maximum transmitted peak power of mobile phones of 1 Watt (W at 1800 MHz and 2 W at 900 MHz respectively, no influence on the ITREL-III was found. Neither the shape of the pulse form changed nor did single pulses fail. Tests with increased transmitted power using CW signals and broadband dipoles have shown that inhibition of the ITREL-III occurs at frequency dependent power levels which are below the emissions of GSM mobile phones. The ITREL-III is essentially more sensitive at 1800 MHz than at 900 MHz. Particularly the frequency range around 1500 MHz shows a very low interference threshold. Conclusion These investigations do not indicate a direct risk for ITREL-III patients using the tested GSM phones. Based on the interference levels found with CW signals, which are below the mobile phone emissions, we recommend similar precautions as for patients with cardiac pacemakers: 1. The phone should be used at the ear at the opposite side of the implant and 2. The patient should avoid carrying the phone close to the implant.

  19. Cytokine Immunopathogenesis of Enterovirus 71 Brain Stem Encephalitis

    Directory of Open Access Journals (Sweden)

    Shih-Min Wang

    2012-01-01

    Full Text Available Enterovirus 71 (EV71 is one of the most important causes of herpangina and hand, foot, and mouth disease. It can also cause severe complications of the central nervous system (CNS. Brain stem encephalitis with pulmonary edema is the severe complication that can lead to death. EV71 replicates in leukocytes, endothelial cells, and dendritic cells resulting in the production of immune and inflammatory mediators that shape innate and acquired immune responses and the complications of disease. Cytokines, as a part of innate immunity, favor the development of antiviral and Th1 immune responses. Cytokines and chemokines play an important role in the pathogenesis EV71 brain stem encephalitis. Both the CNS and the systemic inflammatory responses to infection play important, but distinctly different, roles in the pathogenesis of EV71 pulmonary edema. Administration of intravenous immunoglobulin and milrinone, a phosphodiesterase inhibitor, has been shown to modulate inflammation, to reduce sympathetic overactivity, and to improve survival in patients with EV71 autonomic nervous system dysregulation and pulmonary edema.

  20. Hybrid approach of ventricular assist device and autologous bone marrow stem cells implantation in end-stage ischemic heart failure enhances myocardial reperfusion

    Directory of Open Access Journals (Sweden)

    Khayat Andre

    2011-01-01

    Full Text Available Abstract We challenge the hypothesis of enhanced myocardial reperfusion after implanting a left ventricular assist device together with bone marrow mononuclear stem cells in patients with end-stage ischemic cardiomyopathy. Irreversible myocardial loss observed in ischemic cardiomyopathy leads to progressive cardiac remodelling and dysfunction through a complex neurohormonal cascade. New generation assist devices promote myocardial recovery only in patients with dilated or peripartum cardiomyopathy. In the setting of diffuse myocardial ischemia not amenable to revascularization, native myocardial recovery has not been observed after implantation of an assist device as destination therapy. The hybrid approach of implanting autologous bone marrow stem cells during assist device implantation may eventually improve native cardiac function, which may be associated with a better prognosis eventually ameliorating the need for subsequent heart transplantation. The aforementioned hypothesis has to be tested with well-designed prospective multicentre studies.

  1. Wireless image-data transmission from an implanted image sensor through a living mouse brain by intra body communication

    Science.gov (United States)

    Hayami, Hajime; Takehara, Hiroaki; Nagata, Kengo; Haruta, Makito; Noda, Toshihiko; Sasagawa, Kiyotaka; Tokuda, Takashi; Ohta, Jun

    2016-04-01

    Intra body communication technology allows the fabrication of compact implantable biomedical sensors compared with RF wireless technology. In this paper, we report the fabrication of an implantable image sensor of 625 µm width and 830 µm length and the demonstration of wireless image-data transmission through a brain tissue of a living mouse. The sensor was designed to transmit output signals of pixel values by pulse width modulation (PWM). The PWM signals from the sensor transmitted through a brain tissue were detected by a receiver electrode. Wireless data transmission of a two-dimensional image was successfully demonstrated in a living mouse brain. The technique reported here is expected to provide useful methods of data transmission using micro sized implantable biomedical sensors.

  2. Characterization of TLX expression in neural stem cells and progenitor cells in adult brains.

    Directory of Open Access Journals (Sweden)

    Shengxiu Li

    Full Text Available TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ of adult mouse brains. Then, using a double thymidine analog labeling approach, we showed that almost all of the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX-positive cells in the SVZ represented the thymidine analog-negative, relatively quiescent neural stem cell population. Using cell type markers and short-term BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly dividing type C cells. Furthermore, loss of TLX expression dramatically reduced BrdU label-retaining neural stem cells and the actively dividing neural progenitor cells in the SVZ, but substantially increased GFAP staining and extended GFAP processes. These results suggest that TLX is essential to maintain the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the SVZ lose neural stem cell property upon loss of TLX expression. Understanding the cellular distribution of TLX and its function in specific cell types may provide insights into the development of therapeutic tools for neurodegenerative diseases by targeting TLX in neural stem/progenitors cells.

  3. A novel and generalizable organotypic slice platform to evaluate stem cell potential for targeting pediatric brain tumors

    Directory of Open Access Journals (Sweden)

    Li Shengwen

    2008-05-01

    Full Text Available Abstract Brain tumors are now the leading cause of cancer-related deaths in children under age 15. Malignant gliomas are, for all practical purposes, incurable and new therapeutic approaches are desperately needed. One emerging strategy is to use the tumor tracking capacity inherent in many stem cell populations to deliver therapeutic agents to the brain cancer cells. Current limitations of the stem cell therapy strategy include that stem cells are treated as a single entity and lack of uniform technology is adopted for selection of clinically relevant sub-populations of stem cells. Specifically, therapeutic success relies on the selection of a clinically competent stem cell population based on their capacity of targeting brain tumors. A novel and generalizable organotypic slice platform to evaluate stem cell potential for targeting pediatric brain tumors is proposed to fill the gap in the current work flow of stem cell-based therapy. The organotypic slice platform has advantages of being mimic in vivo model, easier to manipulate to optimize parameters than in vivo models such as rodents and primates. This model serves as a framework to address the discrepancy between anticipated in vivo results and actual in vivo results, a critical barrier to timely progress in the field of the use of stem cells for the treatment of neurological disorders.

  4. Some technical nuances for deep brain stimulator implantation

    Directory of Open Access Journals (Sweden)

    Cole A. Giller, MD, PhD, MBA

    2015-03-01

    Full Text Available Protocols for deep brain stimulator (DBS implantation vary significantly among movement disorders centers despite the need to address similar operative problems. The general steps of this procedure are well accepted, but there are many seemingly minor, yet important nuances not extensively discussed in published descriptions. A classification and the details of the nuances adopted by a single institution may therefore be helpful in providing a basis for discussion and comparison. We describe operative nuances adopted at the Georgia Regents Medical Center (GRMC for DBS implantation that may not be universally employed. The problems of DBS implantation considered here include stereotactic planning, draping, creation and use of the burhole, physiological testing, anchoring of the electrode, financial considerations, and overall technique. Fourteen categories of operative nuances were identified and described in detail. These include the use of specific anatomical relationships for planning, the use of clear and watertight drapes, countersinking of the burhole, the use of gelfoam and tissue glue to seal the burhole, methods to review the entire microelectrode data simultaneously, blinded communication with the patient during macrostimulation, fluoroscopic marking, MRI compatible protection of the electrode tip, financial considerations effecting choice of operative materials, and restriction to a single operator. The majority of these have not been extensively described but may be in use at other centers. The many operative problems arising during DBS implantation can be addressed with specific technical nuances.

  5. Senescence from glioma stem cell differentiation promotes tumor growth

    International Nuclear Information System (INIS)

    Ouchi, Rie; Okabe, Sachiko; Migita, Toshiro; Nakano, Ichiro; Seimiya, Hiroyuki

    2016-01-01

    Glioblastoma (GBM) is a lethal brain tumor composed of heterogeneous cellular populations including glioma stem cells (GSCs) and differentiated non-stem glioma cells (NSGCs). While GSCs are involved in tumor initiation and propagation, NSGCs' role remains elusive. Here, we demonstrate that NSGCs undergo senescence and secrete pro-angiogenic proteins, boosting the GSC-derived tumor formation in vivo. We used a GSC model that maintains stemness in neurospheres, but loses the stemness and differentiates into NSGCs upon serum stimulation. These NSGCs downregulated telomerase, shortened telomeres, and eventually became senescent. The senescent NSGCs released pro-angiogenic proteins, including vascular endothelial growth factors and senescence-associated interleukins, such as IL-6 and IL-8. Conditioned medium from senescent NSGCs promoted proliferation of brain microvascular endothelial cells, and mixed implantation of GSCs and senescent NSGCs into mice enhanced the tumorigenic potential of GSCs. The senescent NSGCs seem to be clinically relevant, because both clinical samples and xenografts of GBM contained tumor cells that expressed the senescence markers. Our data suggest that senescent NSGCs promote malignant progression of GBM in part via paracrine effects of the secreted proteins. - Highlights: • Non-stem glioma cells (NSGCs) lose telomerase and eventually become senescent. • Senescent NSGCs secrete pro-angiogenic proteins, such as VEGFs, IL-6, and IL-8. • Senescent NSGCs enhance the growth of brain microvascular endothelial cells. • Senescent NSGCs enhance the tumorigenic potential of glioma stem cells in vivo.

  6. Senescence from glioma stem cell differentiation promotes tumor growth

    Energy Technology Data Exchange (ETDEWEB)

    Ouchi, Rie [Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Laboratory of Molecular Target Therapy of Cancer, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Okabe, Sachiko; Migita, Toshiro [Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Nakano, Ichiro [Department of Neurosurgery, Comprehensive Cancer Center, University of Alabama at Birmingham, 1824 6th Avenue South, Birmingham, AL 35233 (United States); Seimiya, Hiroyuki, E-mail: hseimiya@jfcr.or.jp [Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan); Laboratory of Molecular Target Therapy of Cancer, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550 (Japan)

    2016-02-05

    Glioblastoma (GBM) is a lethal brain tumor composed of heterogeneous cellular populations including glioma stem cells (GSCs) and differentiated non-stem glioma cells (NSGCs). While GSCs are involved in tumor initiation and propagation, NSGCs' role remains elusive. Here, we demonstrate that NSGCs undergo senescence and secrete pro-angiogenic proteins, boosting the GSC-derived tumor formation in vivo. We used a GSC model that maintains stemness in neurospheres, but loses the stemness and differentiates into NSGCs upon serum stimulation. These NSGCs downregulated telomerase, shortened telomeres, and eventually became senescent. The senescent NSGCs released pro-angiogenic proteins, including vascular endothelial growth factors and senescence-associated interleukins, such as IL-6 and IL-8. Conditioned medium from senescent NSGCs promoted proliferation of brain microvascular endothelial cells, and mixed implantation of GSCs and senescent NSGCs into mice enhanced the tumorigenic potential of GSCs. The senescent NSGCs seem to be clinically relevant, because both clinical samples and xenografts of GBM contained tumor cells that expressed the senescence markers. Our data suggest that senescent NSGCs promote malignant progression of GBM in part via paracrine effects of the secreted proteins. - Highlights: • Non-stem glioma cells (NSGCs) lose telomerase and eventually become senescent. • Senescent NSGCs secrete pro-angiogenic proteins, such as VEGFs, IL-6, and IL-8. • Senescent NSGCs enhance the growth of brain microvascular endothelial cells. • Senescent NSGCs enhance the tumorigenic potential of glioma stem cells in vivo.

  7. Correlation of auditory brain stem response and the MRI measurements in neuro-degenerative disorders

    International Nuclear Information System (INIS)

    Kamei, Hidekazu

    1989-01-01

    The purpose of this study is to elucidate correlations of several MRI measurements of the cranium and brain, functioning as a volume conductor, to the auditory brain stem response (ABR) in neuro-degenerative disorders. The subjects included forty-seven patients with spinocerebellar degeneration (SCD) and sixteen of amyotrophic lateral sclerosis (ALS). Statistically significant positive correlations were found between I-V and III-V interpeak latencies (IPLs) and the area of cranium and brain in the longitudinal section of SCD patients, and between I-III and III-V IPLs and the area in the longitudinal section of those with ALS. And, also there were statistically significant correlations between the amplitude of the V wave and the area of brain stem as well as that of the cranium in the longitudinal section of SCD patients, and between the amplitude of the V wave and the area of the cerebrum in the longitudinal section of ALS. In conclusion, in the ABR, the IPLs were prolonged and the amplitude of the V wave was decreased while the MRI size of the cranium and brain increased. When the ABR is applied to neuro-degenerative disorders, it might be important to consider not only the conduction of the auditory tracts in the brain stem, but also the correlations of the size of the cranium and brain which act as a volume conductor. (author)

  8. Correlation of auditory brain stem response and the MRI measurements in neuro-degenerative disorders

    Energy Technology Data Exchange (ETDEWEB)

    Kamei, Hidekazu (Tokyo Women' s Medical Coll. (Japan))

    1989-06-01

    The purpose of this study is to elucidate correlations of several MRI measurements of the cranium and brain, functioning as a volume conductor, to the auditory brain stem response (ABR) in neuro-degenerative disorders. The subjects included forty-seven patients with spinocerebellar degeneration (SCD) and sixteen of amyotrophic lateral sclerosis (ALS). Statistically significant positive correlations were found between I-V and III-V interpeak latencies (IPLs) and the area of cranium and brain in the longitudinal section of SCD patients, and between I-III and III-V IPLs and the area in the longitudinal section of those with ALS. And, also there were statistically significant correlations between the amplitude of the V wave and the area of brain stem as well as that of the cranium in the longitudinal section of SCD patients, and between the amplitude of the V wave and the area of the cerebrum in the longitudinal section of ALS. In conclusion, in the ABR, the IPLs were prolonged and the amplitude of the V wave was decreased while the MRI size of the cranium and brain increased. When the ABR is applied to neuro-degenerative disorders, it might be important to consider not only the conduction of the auditory tracts in the brain stem, but also the correlations of the size of the cranium and brain which act as a volume conductor. (author).

  9. Brain stem and cerebellar atrophy in chronic progressive neuro-Behçet's disease

    Energy Technology Data Exchange (ETDEWEB)

    Kanoto, Masafumi, E-mail: mkanoto@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Hosoya, Takaaki, E-mail: thosoya@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Toyoguchi, Yuuki, E-mail: c-elegans_0201g@mail.goo.ne.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan); Oda, Atsuko, E-mail: a.oda@med.id.yamagata-u.ac.jp [Department of Diagnostic Radiology, Faculty of Medicine, Yamagata University, Iida-Nishi 2-2-2, 990-9585 Yamagata (Japan)

    2013-01-15

    Purpose: Chronic progressive neuro-Behçet's disease (CPNBD) resembles multiple sclerosis (MS) on patient background and image findings, and therefore is difficult to diagnose. The purpose is to identify the characteristic magnetic resonance imaging (MRI) findings of CPNBD and to clarify the differences between the MRI findings of CPNBD and those of MS. Materials and methods: The subjects consist of a CPNBD group (n = 4; 1 male and 3 females; mean age, 51 y.o.), a MS group (n = 19; 3 males and 16 females; mean age, 45 y.o.) and a normal control group (n = 23; 10 males and 13 females; mean age, 45 y.o.). Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were retrospectively evaluated in each subjects. In middle sagittal brain MR images, the prepontine distance was measured as an indirect index of brain stem and cerebellar atrophy and the pontine and mesencephalic distance was measured as a direct index of brain stem atrophy. These indexes were statistically analyzed. Results: Brain stem atrophy, cerebellar atrophy, and leukoencephalopathy were seen in all CPNBD cases. Prepontine distance was significantly different between the CPNBD group and the MS group (p < 0.05), and between the CPNBD group and the normal control group (p < 0.001). Pontine and mesencephalic distance were significantly different between the CPNBD group and the MS group (p < 0.001, p < 0.01 respectively), and between the CPNBD group and the normal control group (p < 0.001). Conclusions: Chronic progressive neuro-Behçet's disease should be considered in patients with brain stem and cerebellar atrophy in addition to leukoencephalopathy similar to that seen in multiple sclerosis.

  10. Neurosyphilis Involving Cranial Nerves in Brain Stem: 2 Case Reports

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Ji Hye [Dept. of Radiology, Kyung Hee University College of Medicine, Seoul (Korea, Republic of); Choi, Woo Suk; Kim, Eui Jong [Dept. of Radiology, Kyung Hee University Hospital, Seoul (Korea, Republic of); Yoon, Sung Sang; Heo, Sung Hyuk [Dept. of Neurology, Kyung Hee University Hospital, Seoul (Korea, Republic of)

    2012-01-15

    Neurosyphilis uncommonly presents with cranial neuropathies in acute syphilitic meningitis and meningovascular neurosyphilis. We now report two cases in which the meningeal form of neurosyphilis involved cranial nerves in the brain stem: the oculomotor and trigeminal nerve.

  11. Neurosyphilis Involving Cranial Nerves in Brain Stem: 2 Case Reports

    International Nuclear Information System (INIS)

    Jang, Ji Hye; Choi, Woo Suk; Kim, Eui Jong; Yoon, Sung Sang; Heo, Sung Hyuk

    2012-01-01

    Neurosyphilis uncommonly presents with cranial neuropathies in acute syphilitic meningitis and meningovascular neurosyphilis. We now report two cases in which the meningeal form of neurosyphilis involved cranial nerves in the brain stem: the oculomotor and trigeminal nerve.

  12. Spatially Controlled Delivery of siRNAs to Stem Cells in Implants Generated by Multi-Component Additive Manufacturing

    DEFF Research Database (Denmark)

    Andersen, Morten Østergaard; Le, Dang Quang Svend; Chen, Muwan

    2013-01-01

    Additive manufacturing is a promising technique in tissue engineering, as it enables truly individualized implants to be made to fit a particular defect. As previously shown, a feasible strategy to produce complex multicellular tissues is to deposit different small interfering RNA (siRNA) in porous...... implants that are subsequently sutured together. In this study, an additive manufacturing strategy to deposit carbohydrate hydrogels containing different siRNAs is applied into an implant, in a spatially controlled manner. When the obtained structures are seeded with mesenchymal stem (stromal) cells......, the selected siRNAs are delivered to the cells and induces specific and localized gene silencing. Here, it is demonstrated how to replicate part of a patient's spinal cord from a computed tomography scan, using an additive manufacturing technique to produce an implant with compartmentalized si...

  13. Analysis of Neural Stem Cells from Human Cortical Brain Structures In Vitro.

    Science.gov (United States)

    Aleksandrova, M A; Poltavtseva, R A; Marei, M V; Sukhikh, G T

    2016-05-01

    Comparative immunohistochemical analysis of the neocortex from human fetuses showed that neural stem and progenitor cells are present in the brain throughout the gestation period, at least from week 8 through 26. At the same time, neural stem cells from the first and second trimester fetuses differed by the distribution, morphology, growth, and quantity. Immunocytochemical analysis of neural stem cells derived from fetuses at different gestation terms and cultured under different conditions showed their differentiation capacity. Detailed analysis of neural stem cell populations derived from fetuses on gestation weeks 8-9, 18-20, and 26 expressing Lex/SSEA1 was performed.

  14. Brain Implants for Prediction and Mitigation of Epileptic Seizures - Final CRADA Report

    Energy Technology Data Exchange (ETDEWEB)

    Gopalsami, Nachappa

    2016-09-29

    This is a CRADA final report on C0100901 between Argonne National Laboratory and Flint Hills Scientific, LLC of Lawrence, Kansas. Two brain implantable probes, a surface acoustic wave probe and a miniature cooling probe, were designed, built, and tested with excellent results.

  15. A critical review of cell culture strategies for modelling intracortical brain implant material reactions.

    Science.gov (United States)

    Gilmour, A D; Woolley, A J; Poole-Warren, L A; Thomson, C E; Green, R A

    2016-06-01

    The capacity to predict in vivo responses to medical devices in humans currently relies greatly on implantation in animal models. Researchers have been striving to develop in vitro techniques that can overcome the limitations associated with in vivo approaches. This review focuses on a critical analysis of the major in vitro strategies being utilized in laboratories around the world to improve understanding of the biological performance of intracortical, brain-implanted microdevices. Of particular interest to the current review are in vitro models for studying cell responses to penetrating intracortical devices and their materials, such as electrode arrays used for brain computer interface (BCI) and deep brain stimulation electrode probes implanted through the cortex. A background on the neural interface challenge is presented, followed by discussion of relevant in vitro culture strategies and their advantages and disadvantages. Future development of 2D culture models that exhibit developmental changes capable of mimicking normal, postnatal development will form the basis for more complex accurate predictive models in the future. Although not within the scope of this review, innovations in 3D scaffold technologies and microfluidic constructs will further improve the utility of in vitro approaches. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Further In-vitro Characterization of an Implantable Biosensor for Ethanol Monitoring in the Brain

    Directory of Open Access Journals (Sweden)

    Gaia Rocchitta

    2013-07-01

    Full Text Available Ethyl alcohol may be considered one of the most widespread central nervous system (CNS depressants in Western countries. Because of its toxicological and neurobiological implications, the detection of ethanol in brain extracellular fluid (ECF is of great importance. In a previous study, we described the development and characterization of an implantable biosensor successfully used for the real-time detection of ethanol in the brain of freely-moving rats. The implanted biosensor, integrated in a low-cost telemetry system, was demonstrated to be a reliable device for the short-time monitoring of exogenous ethanol in brain ECF. In this paper we describe a further in-vitro characterization of the above-mentioned biosensor in terms of oxygen, pH and temperature dependence in order to complete its validation. With the aim of enhancing ethanol biosensor performance, different enzyme loadings were investigated in terms of apparent ethanol Michaelis-Menten kinetic parameters, viz. IMAX, KM and linear region slope, as well as ascorbic acid interference shielding. The responses of biosensors were studied over a period of 28 days. The overall findings of the present study confirm the original biosensor configuration to be the best of those investigated for in-vivo applications up to one week after implantation.

  17. Development and aging of a brain neural stem cell niche.

    Science.gov (United States)

    Conover, Joanne C; Todd, Krysti L

    2017-08-01

    In the anterior forebrain, along the lateral wall of the lateral ventricles, a neurogenic stem cell niche is found in a region referred to as the ventricular-subventricular zone (V-SVZ). In rodents, robust V-SVZ neurogenesis provides new neurons to the olfactory bulb throughout adulthood; however, with increasing age stem cell numbers are reduced and neurogenic capacity is significantly diminished, but new olfactory bulb neurons continue to be produced even in old age. Humans, in contrast, show little to no new neurogenesis after two years of age and whether V-SVZ neural stem cells persist in the adult human brain remains unclear. Here, we review functional and organizational differences in the V-SVZ stem cell niche of mice and humans, and examine how aging affects the V-SVZ niche and its associated functions. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche

    Science.gov (United States)

    Shao, Yue; Taniguchi, Kenichiro; Gurdziel, Katherine; Townshend, Ryan F.; Xue, Xufeng; Yong, Koh Meng Aw; Sang, Jianming; Spence, Jason R.; Gumucio, Deborah L.; Fu, Jianping

    2017-04-01

    Amniogenesis--the development of amnion--is a critical developmental milestone for early human embryogenesis and successful pregnancy. However, human amniogenesis is poorly understood due to limited accessibility to peri-implantation embryos and a lack of in vitro models. Here we report an efficient biomaterial system to generate human amnion-like tissue in vitro through self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking the in vivo implantation environment. We show that biophysical niche factors act as a switch to toggle hPSC self-renewal versus amniogenesis under self-renewal-permissive biochemical conditions. We identify a unique molecular signature of hPSC-derived amnion-like cells and show that endogenously activated BMP-SMAD signalling is required for the amnion-like tissue development by hPSCs. This study unveils the self-organizing and mechanosensitive nature of human amniogenesis and establishes the first hPSC-based model for investigating peri-implantation human amnion development, thereby helping advance human embryology and reproductive medicine.

  19. External fixation of femoral defects in athymic rats: Applications for human stem cell implantation and bone regeneration

    Directory of Open Access Journals (Sweden)

    Terasa Foo

    2013-01-01

    Full Text Available An appropriate animal model is critical for the research of stem/progenitor cell therapy and tissue engineering for bone regeneration in vivo. This study reports the design of an external fixator and its application to critical-sized femoral defects in athymic rats. The external fixator consists of clamps and screws that are readily available from hardware stores as well as Kirschner wires. A total of 35 rats underwent application of the external fixator with creation of a 6-mm bone defect in one femur of each animal. This model had been used in several separate studies, including implantation of collagen gel, umbilical cord blood mesenchymal stem cells, endothelial progenitor cells, or bone morphogenetic protein-2. One rat developed fracture at the proximal pin site and two rats developed deep tissue infection. Pin loosening was found in nine rats, but it only led to the failure of external fixation in two animals. In 8 to 10 weeks, various degrees of bone growth in the femoral defects were observed in different study groups, from full repair of the bone defect with bone morphogenetic protein-2 implantation to fibrous nonunion with collagen gel implantation. The external fixator used in these studies provided sufficient mechanical stability to the bone defects and had a comparable complication rate in athymic rats as in immunocompetent rats. The external fixator does not interfere with the natural environment of a bone defect. This model is particularly valuable for investigation of osteogenesis of human stem/progenitor cells in vivo.

  20. Brain activation in response to visceral stimulation in rats with amygdala implants of corticosterone: an FMRI study.

    Directory of Open Access Journals (Sweden)

    Anthony C Johnson

    2010-01-01

    Full Text Available Although visceral pain of gastrointestinal (GI origin is the major complaint in patients with irritable bowel syndrome (IBS it remains poorly understood. Brain imaging studies suggest a defect in brain-gut communication in IBS with a greater activation of central arousal circuits including the amygdala. Previously, we found that stereotaxic implantation of corticosterone (CORT onto the amygdala in rats induced anxiety and colonic hypersensitivity. In the present study we used functional magnetic resonance imaging (fMRI to identify specific brain sites activated in a rat model characterized by anxiety and colonic hypersensitivity.Anesthetized male rats received micropellets (30 microg each of either CORT or cholesterol (CHOL, to serve as a control, implanted stereotaxically on the dorsal margin of each amygdala. Seven days later, rats were anesthetized and placed in the fMRI magnet (7T. A series of isobaric colorectal balloon distensions (CRD - 90s 'off', 30s 'on', 8 replicates at two pressures (40 and 60 mmHg were performed in a standard block-design. Cross correlation statistical analysis was used to determine significant differences between distended and non-distended states in CORT and CHOL-treated animals. Analysis of the imaging data demonstrated greater overall brain activation in response to CRD in rats with CORT implants compared to CHOL controls. Additionally, CORT implants produced significant positive bilateral increases in MRI signal in response to CRD in specific nuclei known as integration sites important in anxiety and pain perception.These data indicate that chronic exposure of the amygdala to elevated levels of CORT enhances overall brain activation in response to CRD, and identified other specific brain regions activated in response to mechanical distension of the colon. These results demonstrate the feasibility of performing fMRI imaging in a rodent model that supports clinical observations in IBS patients with enhanced

  1. Brain abscess following dental implant placement via crestal sinus lift - a case report.

    Science.gov (United States)

    Manor, Yifat; Garfunkel, Adi A

    2018-01-01

    To describe a rare case of odontogenic brain abscess. A healthy, 35-year-old male had two dental implants placed in a simultaneously augmented maxillary sinus. One implant failed and the patient developed a maxillary sinusitis that failed to improve following antibiotic treatment at home. The neglected sinus infection led to formation of a brain abscess. The patient was hospitalised only when he had pan sinusitis with neurological signs. Symptoms were headache attacks, a subfebrile fever and a purulent secretion from the left nostril. The osteomeatal complex was blocked, the maxillary sinus was filled with pus and the Schneiderian membrane thickened. The patient was treated with intravenous antibiotic treatment. Computerised tomography (CT) and magnetic resonance imaging (MRI) scans and functional endoscopic sinus surgery (FESS), were implemented. When his conditions worsened, the patient underwent a left frontal mini craniotomy. Following the craniotomy and antibiotic treatment, there was a gradual resolution and the patient was dismissed after 2 months in hospital with no neurological deficit or signs of sinusitis. Maxillary sinusitis following dental implant insertion and concomitant maxillary sinus elevation should be treated immediately and thoroughly since untreated sinusitis may cause life-threatening situations such as a brain abscess. In case of severe infection, clinicians should refer immediately the patient to hospital specialists. Conflict-of-interest statement: The authors have stated explicitly that there are no conflicts of interest. The manuscript was self-funded.

  2. Autologous bone-marrow mesenchymal stem cell implantation and endothelial function in a rabbit ischemic limb model.

    Directory of Open Access Journals (Sweden)

    Shinsuke Mikami

    Full Text Available BACKGROUND: The purpose of this study was to determine whether autologous mesenchymal stem cells (MSCs implantation improves endothelial dysfunction in a rabbit ischemic limb model. METHODS: We evaluated the effect of MSC implantation on limb blood flow (LBF responses to acetylcholine (ACh, an endothelium-dependent vasodilator, and sodium nitroprusside (SNP, an endothelium-independent vasodilator, in rabbits with limb ischemia in which cultured MSCs were implanted (n = 20 or saline was injected as a control group (n = 20. LBF was measured using an electromagnetic flowmeter. A total of 10(6 MSCs were implanted into each ischemic limb. RESULTS: Histological sections of ischemic muscle showed that capillary index (capillary/muscle fiber was greater in the MSC implantation group than in the control group. Laser Doppler blood perfusion index was significantly increased in the MSC implantation group compared with that in the control group. LBF response to ACh was greater in the MSC group than in the control group. After administration of N(G-nitro-L-arginine, a nitric oxide synthase inhibitor, LBF response to ACh was similar in the MSC implantation group and control group. Vasodilatory effects of SNP in the two groups were similar. CONCLUSIONS: These findings suggest that MSC implantation induces angiogenesis and augments endothelium-dependent vasodilation in a rabbit ischemic model through an increase in nitric oxide production.

  3. Radiation control in the intensive care unit for high intensity iridium-192 brain implants

    International Nuclear Information System (INIS)

    Sewchand, W.; Drzymala, R.E.; Amin, P.P.; Salcman, M.; Salazar, O.M.

    1987-01-01

    A bedside lead cubicle was designed to minimize the radiation exposure of intensive care unit staff during routine interstitial brain irradiation by removable, high intensity iridium-192. The cubicle shields the patient without restricting intensive care routines. The design specifications were confirmed by exposure measurements around the shield with an implanted anthropomorphic phantom simulating the patient situation. The cubicle reduces the exposure rate around an implant patient by as much as 90%, with the exposure level not exceeding 0.1 mR/hour/mg of radium-equivalent 192 Ir. Evaluation of data accumulated for the past 3 years has shown that the exposure levels of individual attending nurses are 0.12 to 0.36 mR/mg of radium-equivalent 192 Ir per 12-hour shift. The corresponding range for entire nursing teams varies between 0.18 and 0.26. A radiation control index (exposure per mg of radium-equivalent 192 Ir per nurse-hour) is thus defined for individual nurses and nursing teams; this index is a significant guide to the planning of nurse rotations for brain implant patients with various 192 Ir loads. The bedside shield reduces exposure from 192 Ir implants by a factor of about 20, as expected, and the exposure from the lower energy radioisotope iodine-125 is barely detectable

  4. Nanoparticle-mediated transcriptional modification enhances neuronal differentiation of human neural stem cells following transplantation in rat brain.

    Science.gov (United States)

    Li, Xiaowei; Tzeng, Stephany Y; Liu, Xiaoyan; Tammia, Markus; Cheng, Yu-Hao; Rolfe, Andrew; Sun, Dong; Zhang, Ning; Green, Jordan J; Wen, Xuejun; Mao, Hai-Quan

    2016-04-01

    Strategies to enhance survival and direct the differentiation of stem cells in vivo following transplantation in tissue repair site are critical to realizing the potential of stem cell-based therapies. Here we demonstrated an effective approach to promote neuronal differentiation and maturation of human fetal tissue-derived neural stem cells (hNSCs) in a brain lesion site of a rat traumatic brain injury model using biodegradable nanoparticle-mediated transfection method to deliver key transcriptional factor neurogenin-2 to hNSCs when transplanted with a tailored hyaluronic acid (HA) hydrogel, generating larger number of more mature neurons engrafted to the host brain tissue than non-transfected cells. The nanoparticle-mediated transcription activation method together with an HA hydrogel delivery matrix provides a translatable approach for stem cell-based regenerative therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Effects of neuroinflammation on the regenerative capacity of brain stem cells

    OpenAIRE

    Russo, Isabella; Barlati, Sergio; Bosetti, Francesca

    2011-01-01

    In the adult brain, neurogenesis under physiological conditions occurs in the subventricular zone and in the dentate gyrus. Although the exact molecular mechanisms that regulate neural stem cell proliferation and differentiation are largely unknown, several factors have been shown to affect neurogenesis. Decreased neurogenesis in the hippocampus has been recognized as one of the mechanisms of age-related brain dysfunction. Furthermore, in pathological conditions of the central nervous system ...

  6. Intracranial EEG fluctuates over months after implanting electrodes in human brain

    Science.gov (United States)

    Ung, Hoameng; Baldassano, Steven N.; Bink, Hank; Krieger, Abba M.; Williams, Shawniqua; Vitale, Flavia; Wu, Chengyuan; Freestone, Dean; Nurse, Ewan; Leyde, Kent; Davis, Kathryn A.; Cook, Mark; Litt, Brian

    2017-10-01

    Objective. Implanting subdural and penetrating electrodes in the brain causes acute trauma and inflammation that affect intracranial electroencephalographic (iEEG) recordings. This behavior and its potential impact on clinical decision-making and algorithms for implanted devices have not been assessed in detail. In this study we aim to characterize the temporal and spatial variability of continuous, prolonged human iEEG recordings. Approach. Intracranial electroencephalography from 15 patients with drug-refractory epilepsy, each implanted with 16 subdural electrodes and continuously monitored for an average of 18 months, was included in this study. Time and spectral domain features were computed each day for each channel for the duration of each patient’s recording. Metrics to capture post-implantation feature changes and inflexion points were computed on group and individual levels. A linear mixed model was used to characterize transient group-level changes in feature values post-implantation and independent linear models were used to describe individual variability. Main results. A significant decline in features important to seizure detection and prediction algorithms (mean line length, energy, and half-wave), as well as mean power in the Berger and high gamma bands, was observed in many patients over 100 d following implantation. In addition, spatial variability across electrodes declines post-implantation following a similar timeframe. All selected features decreased by 14-50% in the initial 75 d of recording on the group level, and at least one feature demonstrated this pattern in 13 of the 15 patients. Our findings indicate that iEEG signal features demonstrate increased variability following implantation, most notably in the weeks immediately post-implant. Significance. These findings suggest that conclusions drawn from iEEG, both clinically and for research, should account for spatiotemporal signal variability and that properly assessing the iEEG in

  7. Graphene Functionalized Scaffolds Reduce the Inflammatory Response and Supports Endogenous Neuroblast Migration when Implanted in the Adult Brain.

    Directory of Open Access Journals (Sweden)

    Kun Zhou

    Full Text Available Electroactive materials have been investigated as next-generation neuronal tissue engineering scaffolds to enhance neuronal regeneration and functional recovery after brain injury. Graphene, an emerging neuronal scaffold material with charge transfer properties, has shown promising results for neuronal cell survival and differentiation in vitro. In this in vivo work, electrospun microfiber scaffolds coated with self-assembled colloidal graphene, were implanted into the striatum or into the subventricular zone of adult rats. Microglia and astrocyte activation levels were suppressed with graphene functionalization. In addition, self-assembled graphene implants prevented glial scarring in the brain 7 weeks following implantation. Astrocyte guidance within the scaffold and redirection of neuroblasts from the subventricular zone along the implants was also demonstrated. These findings provide new functional evidence for the potential use of graphene scaffolds as a therapeutic platform to support central nervous system regeneration.

  8. Human umbilical cord blood stem cells and brain-derived neurotrophic factor for optic nerve injury: a biomechanical evaluation

    Directory of Open Access Journals (Sweden)

    Zhong-jun Zhang

    2015-01-01

    Full Text Available Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 10 6 human umbilical cord blood stem cells. After 30 days, the maximum load, maximum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neurotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These findings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, improve biomechanical properties, and contribute to the recovery after injury.

  9. A Randomized Seven-Year Study on Performance of the Stemmed Metal M2a-Magnum and Ceramic C2a-Taper, and the Resurfacing ReCap Hip Implants

    DEFF Research Database (Denmark)

    Borgwardt, Arne; Borgwardt, Lotte; Zerahn, Bo

    2018-01-01

    BACKGROUND: The large-diameter metal-on-metal hip prostheses were expected to have low wear and reduced dislocation rate compared to the traditional metal-on-polyethylene implants. We compare 2 such prostheses, the ReCap resurfacing implant and the M2a-Magnum stemmed implant, with the C2a ceramic......-on-ceramic stemmed implant as to clinical performance, serum concentrations of prosthesis metals, and the durability of the implants in a randomized, controlled clinical trial at 7 years of follow-up. METHODS: All included patients had osteoarthritis. Preoperatively, the size of the implants was estimated from...... of the soft tissue adjacent to the implant as well as MRI with metal artifact reduction sequence (MARS-MRI) when indicated. RESULTS: One hundred fifty-two hips in 146 patients were included. The serum cobalt and chromium concentrations were significantly higher for the 2 metal-on-metal prostheses than...

  10. Brain stem death as the vital determinant for resumption of spontaneous circulation after cardiac arrest in rats.

    Directory of Open Access Journals (Sweden)

    Alice Y W Chang

    Full Text Available BACKGROUND: Spontaneous circulation returns to less than half of adult cardiac arrest victims who received in-hospital resuscitation. One clue for this disheartening outcome arises from the prognosis that asystole invariably takes place, after a time lag, on diagnosis of brain stem death. The designation of brain stem death as the point of no return further suggests that permanent impairment of the brain stem cardiovascular regulatory machinery precedes death. It follows that a crucial determinant for successful revival of an arrested heart is that spontaneous circulation must resume before brain stem death commences. Here, we evaluated the hypothesis that maintained functional integrity of the rostral ventrolateral medulla (RVLM, a neural substrate that is intimately related to brain stem death and central circulatory regulation, holds the key to the vital time-window between cardiac arrest and resumption of spontaneous circulation. METHODOLOGY/PRINCIPAL FINDINGS: An animal model of brain stem death employing the pesticide mevinphos as the experimental insult in Sprague-Dawley rats was used. Intravenous administration of lethal doses of mevinphos elicited an abrupt cardiac arrest, accompanied by elevated systemic arterial pressure and anoxia, augmented neuronal excitability and enhanced microvascular perfusion in RVLM. This period represents the vital time-window between cardiac arrest and resumption of spontaneous circulation in our experimental model. Animals with restored spontaneous circulation exhibited maintained neuronal functionality in RVLM beyond this critical time-window, alongside resumption of baseline tissue oxygen and enhancement of local blood flow. Intriguingly, animals that subsequently died manifested sustained anoxia, diminished local blood flow, depressed mitochondrial electron transport activities and reduced ATP production, leading to necrotic cell death in RVLM. That amelioration of mitochondrial dysfunction and

  11. Endovascular treatment of brain-stem arteriovenous malformations: safety and efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Liu, H.M.; Wang, Y.H.; Chen, Y.F.; Huang, K.M. [Department of Medical Imaging, National Taiwan University Hospital, 7 Chung-Shan South Road, 10016, Taipei (Taiwan); Tu, Y.K. [Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, 7 Chung-Shan South Road, 1001, Taipei (Taiwan)

    2003-09-01

    Our purpose was to evaluate the safety and efficacy of endovascular treatment of brain-stem arteriovenous malformations (AVMs), reviewing six cases managed in the last 5 years. There were four patients who presented with bleeding, one with a progressive neurological deficit and one with obstructive hydrocephalus. Of the six patients, one showed 100%, one 90%, two 75% and two about 50% angiographic obliteration of the AVM after embolisation; the volume decreased about 75% on average. Five patients had a good outcome and one an acceptable outcome, with a mild postprocedure neurological deficit; none had further bleeding during midterm follow-up. Endovascular management of a brain-stem AVM may be an alternative to treatment such as radiosurgery and microsurgery in selected cases. It may be not as risky as previously thought. Embolisation can reduce the size of the AVM and possibly make it more treatable by radiosurgery and decrease the possibility of radiation injury. (orig.)

  12. MRI findings of radiation encephalopathy of brain stem after radiotherapy for nasopharyngeal cancer

    International Nuclear Information System (INIS)

    Liang Changhong; Li Guoye; Huang Biao; Huang Meiping; Zheng Junhui; Tan Shaoheng; Zeng Qiongxin

    1998-01-01

    Purpose: To study MRI findings and clinical manifestation of radiation encephalopathy (RE) of brain stem. Methods: MRI findings and clinical symptoms in 51 patients with RE of brain stem after radiotherapy for nasopharyngeal cancer were reviewed. Results: Clinical symptoms included number weakness or paralysis in the limbs and symptoms of damaged cranial nerves. All lesions appeared hypo- or iso-intense on spin echo(SE) T 1 -weighted images and inhomogeneous and mixed hyper- and iso-intense on Turbo spin echo (TSE) T 2 -weighted images. The lesions were located in mesencephalon, pons, medulla, basilar part of pons, basilar part of pons and medulla oblongata in 2,7,3,9 and 30 patients respectively. The enhancement patterns included irregular rings in 39 patients, spotty in 3 and no enhancement in 9 patients. Mass effect was minimal in all patients. On follow-up MRI, the lesions disappeared in 4 patients, did not change in size and shape in 8 patients and enlarged in 2 patients. Conclusion: MRI could demonstrate the characteristic findings of RE of brain stem. MRI findings sometimes are not consistent with the clinical symptoms

  13. Implanted hair follicle stem cells form Schwann cells that support repair of severed peripheral nerves.

    Science.gov (United States)

    Amoh, Yasuyuki; Li, Lingna; Campillo, Raul; Kawahara, Katsumasa; Katsuoka, Kensei; Penman, Sheldon; Hoffman, Robert M

    2005-12-06

    The hair follicle bulge area is an abundant, easily accessible source of actively growing, pluripotent adult stem cells. Nestin, a protein marker for neural stem cells, also is expressed in follicle stem cells and their immediate, differentiated progeny. The fluorescent protein GFP, whose expression is driven by the nestin regulatory element in transgenic mice, served to mark the follicle cell fate. The pluripotent nestin-driven GFP stem cells are positive for the stem cell marker CD34 but negative for keratinocyte marker keratin 15, suggesting their relatively undifferentiated state. These cells can differentiate into neurons, glia, keratinocytes, smooth muscle cells, and melanocytes in vitro. In vivo studies show the nestin-driven GFP hair follicle stem cells can differentiate into blood vessels and neural tissue after transplantation to the subcutis of nude mice. Equivalent hair follicle stem cells derived from transgenic mice with beta-actin-driven GFP implanted into the gap region of a severed sciatic nerve greatly enhance the rate of nerve regeneration and the restoration of nerve function. The follicle cells transdifferentiate largely into Schwann cells, which are known to support neuron regrowth. Function of the rejoined sciatic nerve was measured by contraction of the gastrocnemius muscle upon electrical stimulation. After severing the tibial nerve and subsequent transplantation of hair follicle stem cells, walking print length and intermediate toe spread significantly recovered, indicating that the transplanted mice recovered the ability to walk normally. These results suggest that hair follicle stem cells provide an important, accessible, autologous source of adult stem cells for regenerative medicine.

  14. MRI measurements of the brain stem and cerebellum in high functioning autistic children

    International Nuclear Information System (INIS)

    Hashimoto, Toshiaki; Tayama, Masanobu; Miyazaki, Masahito; Murakawa, Kazuyoshi; Kuroda, Yasuhiro

    1994-01-01

    To determine involvements of the brain stem and/or cerebellum in autism, we compared midsagittal magnetic resonance images of the brains of high functioning autistic children with those of normal controls. We found that the midbrain and medulla oblongata were significantly smaller in these autistic children than in the control children. The pons area did not differ between the two groups, nor was there any difference in the cerebellar vermis area. The ratio of the brain stem and cerebellum to the posterior fossa area did not differ significantly between the high functioning autistic and the control children. The development of the cerebellar vermis area was delayed in autistic children as compared with that in the control children. Thus, it was suggested that significant anatomical changes in the midbrain and medulla oblongata existed in the autistic children. (author)

  15. MRI measurements of the brain stem and cerebellum in high functioning autistic children

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Toshiaki; Tayama, Masanobu; Miyazaki, Masahito; Murakawa, Kazuyoshi; Kuroda, Yasuhiro [Tokushima Univ. (Japan). School of Medicine

    1994-01-01

    To determine involvements of the brain stem and/or cerebellum in autism, we compared midsagittal magnetic resonance images of the brains of high functioning autistic children with those of normal controls. We found that the midbrain and medulla oblongata were significantly smaller in these autistic children than in the control children. The pons area did not differ between the two groups, nor was there any difference in the cerebellar vermis area. The ratio of the brain stem and cerebellum to the posterior fossa area did not differ significantly between the high functioning autistic and the control children. The development of the cerebellar vermis area was delayed in autistic children as compared with that in the control children. Thus, it was suggested that significant anatomical changes in the midbrain and medulla oblongata existed in the autistic children. (author).

  16. Gingival Mesenchymal Stem Cell (GMSC) Delivery System Based on RGD-Coupled Alginate Hydrogel with Antimicrobial Properties: A Novel Treatment Modality for Peri-Implantitis.

    Science.gov (United States)

    Diniz, Ivana M A; Chen, Chider; Ansari, Sahar; Zadeh, Homayoun H; Moshaverinia, Maryam; Chee, Daniel; Marques, Márcia M; Shi, Songtao; Moshaverinia, Alireza

    2016-02-01

    Peri-implantitis is one of the most common inflammatory complications in dental implantology. Similar to periodontitis, in peri-implantitis, destructive inflammatory changes take place in the tissues surrounding a dental implant. Bacterial flora at the failing implant sites resemble the pathogens in periodontal disease and consist of Gram-negative anaerobic bacteria including Aggregatibacter actinomycetemcomitans (Aa). Here we demonstrate the effectiveness of a silver lactate (SL)-containing RGD-coupled alginate hydrogel scaffold as a promising stem cell delivery vehicle with antimicrobial properties. Gingival mesenchymal stem cells (GMSCs) or human bone marrow mesenchymal stem cells (hBMMSCs) were encapsulated in SL-loaded alginate hydrogel microspheres. Stem cell viability, proliferation, and osteo-differentiation capacity were analyzed. Our results showed that SL exhibited antimicrobial properties against Aa in a dose-dependent manner, with 0.50 mg/ml showing the greatest antimicrobial properties while still maintaining cell viability. At this concentration, SL-containing alginate hydrogel was able to inhibit Aa growth on the surface of Ti discs and significantly reduce the bacterial load in Aa suspensions. Silver ions were effectively released from the SL-loaded alginate microspheres for up to 2 weeks. Osteogenic differentiation of GMSCs and hBMMSCs encapsulated in the SL-loaded alginate microspheres were confirmed by the intense mineral matrix deposition and high expression of osteogenesis-related genes. Taken together, our findings confirm that GMSCs encapsulated in RGD-modified alginate hydrogel containing SL show promise for bone tissue engineering with antimicrobial properties against Aa bacteria in vitro. © 2015 by the American College of Prosthodontists.

  17. A subcutaneous cellular implant for passive immunization against amyloid-β reduces brain amyloid and tau pathologies.

    Science.gov (United States)

    Lathuilière, Aurélien; Laversenne, Vanessa; Astolfo, Alberto; Kopetzki, Erhard; Jacobsen, Helmut; Stampanoni, Marco; Bohrmann, Bernd; Schneider, Bernard L; Aebischer, Patrick

    2016-05-01

    Passive immunization against misfolded toxic proteins is a promising approach to treat neurodegenerative disorders. For effective immunotherapy against Alzheimer's disease, recent clinical data indicate that monoclonal antibodies directed against the amyloid-β peptide should be administered before the onset of symptoms associated with irreversible brain damage. It is therefore critical to develop technologies for continuous antibody delivery applicable to disease prevention. Here, we addressed this question using a bioactive cellular implant to deliver recombinant anti-amyloid-β antibodies in the subcutaneous tissue. An encapsulating device permeable to macromolecules supports the long-term survival of myogenic cells over more than 10 months in immunocompetent allogeneic recipients. The encapsulated cells are genetically engineered to secrete high levels of anti-amyloid-β antibodies. Peripheral implantation leads to continuous antibody delivery to reach plasma levels that exceed 50 µg/ml. In a proof-of-concept study, we show that the recombinant antibodies produced by this system penetrate the brain and bind amyloid plaques in two mouse models of the Alzheimer's pathology. When encapsulated cells are implanted before the onset of amyloid plaque deposition in TauPS2APP mice, chronic exposure to anti-amyloid-β antibodies dramatically reduces amyloid-β40 and amyloid-β42 levels in the brain, decreases amyloid plaque burden, and most notably, prevents phospho-tau pathology in the hippocampus. These results support the use of encapsulated cell implants for passive immunotherapy against the misfolded proteins, which accumulate in Alzheimer's disease and other neurodegenerative disorders. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Brain stem auditory evoked responses in chronic alcoholics.

    OpenAIRE

    Chan, Y W; McLeod, J G; Tuck, R R; Feary, P A

    1985-01-01

    Brain stem auditory evoked responses (BAERs) were performed on 25 alcoholic patients with Wernicke-Korsakoff syndrome, 56 alcoholic patients without Wernicke-Korsakoff syndrome, 24 of whom had cerebellar ataxia, and 37 control subjects. Abnormal BAERs were found in 48% of patients with Wernicke-Korsakoff syndrome, in 25% of alcoholic patients without Wernicke-Korsakoff syndrome but with cerebellar ataxia, and in 13% of alcoholic patients without Wernicke-Korsakoff syndrome or ataxia. The mean...

  19. Pediatric brain stem tumors: analysis of 25 cases

    International Nuclear Information System (INIS)

    Pinel, M.I.S.; Kalifa, C.; Sarrazin, D.; Lemerle, J.

    1985-01-01

    The charts of 25 pediatric patients with brain stem tumors have been reviewed. The use of computed tomography was found to have been valuable in diagnosis and follow-up, as well as in the design of radiation therapy portals. Radiotherapy and combination chemotherapy with VM-26 (4'-1 demethyl-epipodophyllo toxin B-D-thenylidene glucoside) and CCNU(1-2-chloroethyl-methyl-3-Cyclohexyl-1-nitrosourea) were the treatment employed. (M.A.C.) [pt

  20. The endogenous regenerative capacity of the damaged newborn brain: boosting neurogenesis with mesenchymal stem cell treatment.

    Science.gov (United States)

    Donega, Vanessa; van Velthoven, Cindy T J; Nijboer, Cora H; Kavelaars, Annemieke; Heijnen, Cobi J

    2013-05-01

    Neurogenesis continues throughout adulthood. The neurogenic capacity of the brain increases after injury by, e.g., hypoxia-ischemia. However, it is well known that in many cases brain damage does not resolve spontaneously, indicating that the endogenous regenerative capacity of the brain is insufficient. Neonatal encephalopathy leads to high mortality rates and long-term neurologic deficits in babies worldwide. Therefore, there is an urgent need to develop more efficient therapeutic strategies. The latest findings indicate that stem cells represent a novel therapeutic possibility to improve outcome in models of neonatal encephalopathy. Transplanted stem cells secrete factors that stimulate and maintain neurogenesis, thereby increasing cell proliferation, neuronal differentiation, and functional integration. Understanding the molecular and cellular mechanisms underlying neurogenesis after an insult is crucial for developing tools to enhance the neurogenic capacity of the brain. The aim of this review is to discuss the endogenous capacity of the neonatal brain to regenerate after a cerebral ischemic insult. We present an overview of the molecular and cellular mechanisms underlying endogenous regenerative processes during development as well as after a cerebral ischemic insult. Furthermore, we will consider the potential to use stem cell transplantation as a means to boost endogenous neurogenesis and restore brain function.

  1. The brain stem function in patients with brain bladder; Clinical evaluation using dynamic CT scan and auditory brainstem response

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Toshihiro (Yokohama City Univ. (Japan). Faculty of Medicine)

    1990-11-01

    A syndrome of detrusor-sphincter dyssynergia (DSD) is occasionally found in patients with brain bladder. To evaluate the brain stem function in cases of brain bladder, urodynamic study, dynamic CT scan of the brain stem (DCT) and auditory brainstem response (ABR) were performed. The region of interest of DCT aimed at the posterolateral portion of the pons. The results were analysed in contrast with the presense of DSD in urodynamic study. DCT studies were performed in 13 cases with various brain diseases and 5 control cases without neurological diseases. Abnormal patterns of the time-density curve consisted of low peak value, prolongation of filling time and low rapid washout ratio (low clearance ratio) of the contrast medium. Four of 6 cases with DSD showed at least one of the abnormal patterns of the time-density curve bilaterally. In 7 cases without DSD none showed bilateral abnormality of the curve and in 2 of 7 cases only unilateral abnormality was found. ABR was performed in 8 patients with brain diseases. The interpeak latency of the wave I-V (I-V IPL) was considered to be prolonged in 2 cases with DSD compared to that of 4 without DSD. In 2 cases with DSD who had normal DCT findings, measurement of the I-V IPL was impossible due to abnormal pattern of the ABR wave. Above mentioned results suggests the presence of functional disturbance at the posterolateral portion of the pons in cases of brain bladder with DSD. (author).

  2. Stem cells technology: a powerful tool behind new brain treatments.

    Science.gov (United States)

    Duru, Lucienne N; Quan, Zhenzhen; Qazi, Talal Jamil; Qing, Hong

    2018-06-18

    Stem cell research has recently become a hot research topic in biomedical research due to the foreseen unlimited potential of stem cells in tissue engineering and regenerative medicine. For many years, medicine has been facing intense challenges, such as an insufficient number of organ donations that is preventing clinicians to fulfill the increasing needs. To try and overcome this regrettable matter, research has been aiming at developing strategies to facilitate the in vitro culture and study of stem cells as a tool for tissue regeneration. Meanwhile, new developments in the microfluidics technology brought forward emerging cell culture applications that are currently allowing for a better chemical and physical control of cellular microenvironment. This review presents the latest developments in stem cell research that brought new therapies to the clinics and how the convergence of the microfluidics technology with stem cell research can have positive outcomes on the fields of regenerative medicine and high-throughput screening. These advances will bring new translational solutions for drug discovery and will upgrade in vitro cell culture to a new level of accuracy and performance. We hope this review will provide new insights into the understanding of new brain treatments from the perspective of stem cell technology especially regarding regenerative medicine and tissue engineering.

  3. Brain-stem evoked potentials and noise effects in seagulls.

    Science.gov (United States)

    Counter, S A

    1985-01-01

    Brain-stem auditory evoked potentials (BAEP) recorded from the seagull were large-amplitude, short-latency, vertex-positive deflections which originate in the eighth nerve and several brain-stem nuclei. BAEP waveforms were similar in latency and configurations to that reported for certain other lower vertebrates and some mammals. BAEP recorded at several pure tone frequencies throughout the seagull's auditory spectrum showed an area of heightened auditory sensitivity between 1 and 3 kHz. This range was also found to be the primary bandwidth of the vocalization output of young seagulls. Masking by white noise and pure tones had remarkable effects on several parameters of the BAEP. In general, the tone- and click-induced BAEP were either reduced or obliterated by both pure tone and white noise maskers of specific signal to noise ratios and high intensity levels. The masking effects observed in this study may be related to the manner in which seagulls respond to intense environmental noise. One possible conclusion is that intense environmental noise, such as aircraft engine noise, may severely alter the seagull's localization apparatus and induce sonogenic stress, both of which could cause collisions with low-flying aircraft.

  4. Efficient and rapid derivation of primitive neural stem cells and generation of brain subtype neurons from human pluripotent stem cells.

    Science.gov (United States)

    Yan, Yiping; Shin, Soojung; Jha, Balendu Shekhar; Liu, Qiuyue; Sheng, Jianting; Li, Fuhai; Zhan, Ming; Davis, Janine; Bharti, Kapil; Zeng, Xianmin; Rao, Mahendra; Malik, Nasir; Vemuri, Mohan C

    2013-11-01

    Human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, are unique cell sources for disease modeling, drug discovery screens, and cell therapy applications. The first step in producing neural lineages from hPSCs is the generation of neural stem cells (NSCs). Current methods of NSC derivation involve the time-consuming, labor-intensive steps of an embryoid body generation or coculture with stromal cell lines that result in low-efficiency derivation of NSCs. In this study, we report a highly efficient serum-free pluripotent stem cell neural induction medium that can induce hPSCs into primitive NSCs (pNSCs) in 7 days, obviating the need for time-consuming, laborious embryoid body generation or rosette picking. The pNSCs expressed the neural stem cell markers Pax6, Sox1, Sox2, and Nestin; were negative for Oct4; could be expanded for multiple passages; and could be differentiated into neurons, astrocytes, and oligodendrocytes, in addition to the brain region-specific neuronal subtypes GABAergic, dopaminergic, and motor neurons. Global gene expression of the transcripts of pNSCs was comparable to that of rosette-derived and human fetal-derived NSCs. This work demonstrates an efficient method to generate expandable pNSCs, which can be further differentiated into central nervous system neurons and glia with temporal, spatial, and positional cues of brain regional heterogeneity. This method of pNSC derivation sets the stage for the scalable production of clinically relevant neural cells for cell therapy applications in good manufacturing practice conditions.

  5. Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure.

    Science.gov (United States)

    Cauley, Edmund; Wang, Xin; Dyavanapalli, Jhansi; Sun, Ke; Garrott, Kara; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Mendelowitz, David

    2015-10-01

    Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases. Copyright © 2015 the American Physiological Society.

  6. Implantation of Induced Pluripotent Stem Cell-Derived Tracheal Epithelial Cells.

    Science.gov (United States)

    Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Yoshie, Susumu; Nakamura, Ryosuke; Otsuki, Koshi; Murono, Shigeyuki; Omori, Koichi

    2017-07-01

    Compared with using autologous tissue, the use of artificial materials in the regeneration of tracheal defects is minimally invasive. However, this technique requires early epithelialization on the inner side of the artificial trachea. After differentiation from induced pluripotent stem cells (iPSCs), tracheal epithelial tissues may be used to produce artificial tracheas. Herein, we aimed to demonstrate that after differentiation from fluorescent protein-labeled iPSCs, tracheal epithelial tissues survived in nude rats with tracheal defects. Red fluorescent tdTomato protein was electroporated into mouse iPSCs to produce tdTomato-labeled iPSCs. Embryoid bodies derived from these iPSCs were then cultured in differentiation medium supplemented with growth factors, followed by culture on air-liquid interfaces for further differentiation into tracheal epithelium. The cells were implanted with artificial tracheas into nude rats with tracheal defects on day 26 of cultivation. On day 7 after implantation, the tracheas were exposed and examined histologically. Tracheal epithelial tissue derived from tdTomato-labeled iPSCs survived in the tracheal defects. Moreover, immunochemical analyses showed that differentiated tissues had epithelial structures similar to those of proximal tracheal tissues. After differentiation from iPSCs, tracheal epithelial tissues survived in rat bodies, warranting the use of iPSCs for epithelial regeneration in tracheal defects.

  7. Tetherless near-infrared control of brain activity in behaving animals using fully implantable upconversion microdevices.

    Science.gov (United States)

    Wang, Ying; Lin, Xudong; Chen, Xi; Chen, Xian; Xu, Zhen; Zhang, Wenchong; Liao, Qinghai; Duan, Xin; Wang, Xin; Liu, Ming; Wang, Feng; He, Jufang; Shi, Peng

    2017-10-01

    Many nanomaterials can be used as sensors or transducers in biomedical research and they form the essential components of transformative novel biotechnologies. In this study, we present an all-optical method for tetherless remote control of neural activity using fully implantable micro-devices based on upconversion technology. Upconversion nanoparticles (UCNPs) were used as transducers to convert near-infrared (NIR) energy to visible light in order to stimulate neurons expressing different opsin proteins. In our setup, UCNPs were packaged in a glass micro-optrode to form an implantable device with superb long-term biocompatibility. We showed that remotely applied NIR illumination is able to reliably trigger spiking activity in rat brains. In combination with a robotic laser projection system, the upconversion-based tetherless neural stimulation technique was implemented to modulate brain activity in various regions, including the striatum, ventral tegmental area, and visual cortex. Using this system, we were able to achieve behavioral conditioning in freely moving animals. Notably, our microscale device was at least one order of magnitude smaller in size (∼100 μm in diameter) and two orders of magnitude lighter in weight (less than 1 mg) than existing wireless optogenetic devices based on light-emitting diodes. This feature allows simultaneous implantation of multiple UCNP-optrodes to achieve modulation of brain function to control complex animal behavior. We believe that this technology not only represents a novel practical application of upconversion nanomaterials, but also opens up new possibilities for remote control of neural activity in the brains of behaving animals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Magnetic stem cell targeting to the inner ear

    Science.gov (United States)

    Le, T. N.; Straatman, L.; Yanai, A.; Rahmanian, R.; Garnis, C.; Häfeli, U. O.; Poblete, T.; Westerberg, B. D.; Gregory-Evans, K.

    2017-12-01

    Severe sensorineural deafness is often accompanied by a loss of auditory neurons in addition to injury of the cochlear epithelium and hair cell loss. Cochlear implant function however depends on a healthy complement of neurons and their preservation is vital in achieving optimal results. We have developed a technique to target mesenchymal stem cells (MSCs) to a deafened rat cochlea. We then assessed the neuroprotective effect of systematically delivered MSCs on the survival and function of spiral ganglion neurons (SGNs). MSCs were labeled with superparamagnetic nanoparticles, injected via the systemic circulation, and targeted using a magnetized cochlea implant and external magnet. Neurotrophic factor concentrations, survival of SGNs, and auditory function were assessed at 1 week and 4 weeks after treatments and compared against multiple control groups. Significant numbers of magnetically targeted MSCs (>30 MSCs/section) were present in the cochlea with accompanied elevation of brain-derived neurotrophic factor and glial cell-derived neurotrophic factor levels (p < 0.001). In addition we saw improved survival of SGNs (approximately 80% survival at 4 weeks). Hearing threshold levels in magnetically targeted rats were found to be significantly better than those of control rats (p < 0.05). These results indicate that magnetic targeting of MSCs to the cochlea can be accomplished with a magnetized cochlear permalloy implant and an external magnet. The targeted stem cells release neurotrophic factors which results in improved SGN survival and hearing recovery. Combining magnetic cell-based therapy and cochlear implantation may improve cochlear implant function in treating deafness.

  9. Auditory Brain Stem Processing in Reptiles and Amphibians: Roles of Coupled Ears

    DEFF Research Database (Denmark)

    Willis, Katie L.; Christensen-Dalsgaard, Jakob; Carr, Catherine

    2014-01-01

    Comparative approaches to the auditory system have yielded great insight into the evolution of sound localization circuits, particularly within the nonmammalian tetrapods. The fossil record demonstrates multiple appearances of tympanic hearing, and examination of the auditory brain stem of various...... groups can reveal the organizing effects of the ear across taxa. If the peripheral structures have a strongly organizing influence on the neural structures, then homologous neural structures should be observed only in groups with a homologous tympanic ear. Therefore, the central auditory systems...... of anurans (frogs), reptiles (including birds), and mammals should all be more similar within each group than among the groups. Although there is large variation in the peripheral auditory system, there is evidence that auditory brain stem nuclei in tetrapods are homologous and have similar functions among...

  10. Thrombospondin 2-null mice display an altered brain foreign body response to polyvinyl alcohol sponge implants

    International Nuclear Information System (INIS)

    Tian Weiming; Kyriakides, Themis R

    2009-01-01

    Thrombospondin (TSP)-2 is a matricellular protein that participates in the processes of tissue repair and the foreign body response. In addition, TSP2 has been shown to influence synaptogenesis and recovery of the brain following stroke. In the present study we investigated the response following the implantation of polyvinyl alcohol (PVA) sponges in the brain. PVA sponges were implanted into the brain cortex of wild type and TSP2-null mice for a period of 4 and 8 weeks and the response was analyzed by histochemistry and quantitative immunohistochemistry. TSP2 expression was detected in the interstices of the sponge and co-localized with the extracellular matrix and astrocytes. PVA sponge invasion in TSP2-null mice was characterized by dense deposition of extracellular matrix and increased invasion of reactive astrocytes and macrophages/microglia. Furthermore, the angiogenic response was elevated and the detection of mouse serum albumin (MSA) in the brain cortex indicated excessive vessel leakage, suggesting that TSP2 plays a role in the repair/maintenance of the blood brain barrier. Finally, immunostaining demonstrated an increase in the levels of matrix metalloproteinase (MMP)-2 and MMP-9. Taken together, our observations support a role for TSP2 as critical determinant of the brain response to biomaterials.

  11. Syringe needle skull penetration reduces brain injuries and secondary inflammation following intracerebral neural stem cell transplantation

    OpenAIRE

    Gao, Mou; Dong, Qin; Zhang, Hongtian; Yang, Yang; Zhu, Jianwei; Yang, Zhijun; Xu, Minhui; Xu, Ruxiang

    2017-01-01

    Intracerebral neural stem cell (NSC) transplantation is beneficial for delivering stem cell grafts effectively, however, this approach may subsequently result in brain injury and secondary inflammation. To reduce the risk of promoting brain injury and secondary inflammation, two methods were compared in the present study. Murine skulls were penetrated using a drill on the left side and a syringe needle on the right. Mice were randomly divided into three groups (n=84/group): Group A, receiving...

  12. [Isolation and identification of brain tumor stem cells from human brain neuroepithelial tumors].

    Science.gov (United States)

    Fang, Jia-sheng; Deng, Yong-wen; Li, Ming-chu; Chen, Feng-Hua; Wang, Yan-jin; Lu, Ming; Fang, Fang; Wu, Jun; Yang, Zhuan-yi; Zhou, Xang-yang; Wang, Fei; Chen, Cheng

    2007-01-30

    To establish a simplified culture system for the isolation of brain tumor stem cells (BTSCs) from the tumors of human neuroepithelial tissue, to observe the growth and differentiation pattern of BTSCs, and to investigate their expression of the specific markers. Twenty-six patients with brain neuroepithelial tumors underwent tumor resection. Two pieces of tumor tissues were taken from each tumor to be dissociated, triturated into single cells in sterile DMEM-F12 medium, and then filtered. The tumor cells were seeded at a concentration of 200,000 viable cells per mL into serum-free DMEM-F12 medium simply supplemented with B27, human basic fibroblast growth factor (20 microg/L), human epidermal growth factor (20 microg /L), insulin (4 U/L), L-glutamine, penicillin and streptomycin. After the primary brain tumor spheres (BTSs) were generated, they were triturated again and passed in fresh medium. Limiting dilution assay was performed to observe the monoclone formation. 5-bromodeoxyuridine (BrdU) incorporation test was performed to observe the proliferation of the BTS. The BTSCs were cultured in mitogen-free DMEM-F12 medium supplemented with 10% fetal bovine serum to observe their differentiation. Immunocytochemistry was used to examine the expression of CD133 and nestin, specific markers of BTSC, and the rate of CD133 positive cells. Only a minority of subsets of cells from the tumors of neuroepithelial tissue had the capacity to survive, proliferate, and generate free-floating neurosphere-like BTSs in the simplified serum-free medium. These cells attached to the poly-L-lysine coated coverslips in the serum-supplemented medium and differentiated. The BTSCs were CD133 and nestin positive. The rate of CD133 positive cells in the tumor specimens was (21 +/- 6.2)% - (38 +/- 7.0)%. A new simplified culture system for the isolation of BTSCs is established. The tumors of human neuroepithelial tissue contain CD133 and nestin positive tumor stem cells which can be isolated

  13. Delayed radiation-induced necrosis of the brain stem; A case report

    Energy Technology Data Exchange (ETDEWEB)

    Yukawa, Osamu; Kodama, Yasunori; Kyoda, Jun; Yuki, Kiyoshi; Taniguchi, Eiji; Katayama, Shoichi; Hiroi, Tadashi (National Kure Hospital, Hiroshima (Japan)); Uozumi, Toru

    1993-03-01

    A 46-year-old man had surgery for a mixed glioma of the frontotemporal lobe. Postoperatively he received 50 Gy of irradiation. Sixteen months later he developed left hemiparesis and left facial palsy. MRI revealed lesion brain stem and basal ganglia. Despite chemotherapy and an additional 50 Gy dose, the patient deteriorated. Autopsy revealed a wide spread radiation-induced necrosis in the right cerebral hemisphere, midbrain and pons. In radiation therapy, great care must be taken to protect the normal brain tissue. (author).

  14. Electrospun nanofibrous scaffolds increase the efficacy of stem cell-mediated therapy of surgically resected glioblastoma

    Science.gov (United States)

    Bagó, Juli R.; Pegna, Guillaume J.; Okolie, Onyi; Mohiti-Asli, Mahsa; Loboa, Elizabeth G.; Hingtgen, Shawn D.

    2017-01-01

    Engineered stem cell (SC)-based therapy holds enormous promise for treating the incurable brain cancer glioblastoma (GBM). Retaining the cytotoxic SCs in the surgical cavity after GBM resection is one of the greatest challenges to this approach. Here, we describe a biocompatible electrospun nanofibrous scaffold (bENS) implant capable of delivering and retaining tumor-homing cytotoxic stem cells that suppress recurrence of post-surgical GBM. As a new approach to GBM therapy, we created poly(l-lactic acid) (PLA) bENS bearing drug-releasing human mesenchymal stem cells (hMSCs). We discovered that bENS-based implant increased hMSC retention in the surgical cavity 5-fold and prolonged persistence 3-fold compared to standard direct injection using our mouse model of GBM surgical resection/recurrence. Time-lapse imaging showed cytotoxic hMSC/bENS treatment killed co-cultured human GBM cells, and allowed hMSCs to rapidly migrate off the scaffolds as they homed to GBMs. In vivo, bENS loaded with hMSCs releasing the anti-tumor protein TRAIL (bENSsTR) reduced the volume of established GBM xenografts 3-fold. Mimicking clinical GBM patient therapy, lining the post-operative GBM surgical cavity with bENSsTR implants inhibited the re-growth of residual GBM foci 2.3-fold and prolonged post-surgical median survival from 13.5 to 31 days in mice. These results suggest that nanofibrous-based SC therapies could be an innovative new approach to improve the outcomes of patients suffering from terminal brain cancer. PMID:27016620

  15. Implantable fiber-optic interface for parallel multisite long-term optical dynamic brain interrogation in freely moving mice

    Science.gov (United States)

    Doronina-Amitonova, L. V.; Fedotov, I. V.; Ivashkina, O. I.; Zots, M. A.; Fedotov, A. B.; Anokhin, K. V.; Zheltikov, A. M.

    2013-01-01

    Seeing the big picture of functional responses within large neural networks in a freely functioning brain is crucial for understanding the cellular mechanisms behind the higher nervous activity, including the most complex brain functions, such as cognition and memory. As a breakthrough toward meeting this challenge, implantable fiber-optic interfaces integrating advanced optogenetic technologies and cutting-edge fiber-optic solutions have been demonstrated, enabling a long-term optogenetic manipulation of neural circuits in freely moving mice. Here, we show that a specifically designed implantable fiber-optic interface provides a powerful tool for parallel long-term optical interrogation of distinctly separate, functionally different sites in the brain of freely moving mice. This interface allows the same groups of neurons lying deeply in the brain of a freely behaving mouse to be reproducibly accessed and optically interrogated over many weeks, providing a long-term dynamic detection of genome activity in response to a broad variety of pharmacological and physiological stimuli. PMID:24253232

  16. Simultaneous bilateral stereotactic procedure for deep brain stimulation implants: a significant step for reducing operation time.

    Science.gov (United States)

    Fonoff, Erich Talamoni; Azevedo, Angelo; Angelos, Jairo Silva Dos; Martinez, Raquel Chacon Ruiz; Navarro, Jessie; Reis, Paul Rodrigo; Sepulveda, Miguel Ernesto San Martin; Cury, Rubens Gisbert; Ghilardi, Maria Gabriela Dos Santos; Teixeira, Manoel Jacobsen; Lopez, William Omar Contreras

    2016-07-01

    OBJECT Currently, bilateral procedures involve 2 sequential implants in each of the hemispheres. The present report demonstrates the feasibility of simultaneous bilateral procedures during the implantation of deep brain stimulation (DBS) leads. METHODS Fifty-seven patients with movement disorders underwent bilateral DBS implantation in the same study period. The authors compared the time required for the surgical implantation of deep brain electrodes in 2 randomly assigned groups. One group of 28 patients underwent traditional sequential electrode implantation, and the other 29 patients underwent simultaneous bilateral implantation. Clinical outcomes of the patients with Parkinson's disease (PD) who had undergone DBS implantation of the subthalamic nucleus using either of the 2 techniques were compared. RESULTS Overall, a reduction of 38.51% in total operating time for the simultaneous bilateral group (136.4 ± 20.93 minutes) as compared with that for the traditional consecutive approach (220.3 ± 27.58 minutes) was observed. Regarding clinical outcomes in the PD patients who underwent subthalamic nucleus DBS implantation, comparing the preoperative off-medication condition with the off-medication/on-stimulation condition 1 year after the surgery in both procedure groups, there was a mean 47.8% ± 9.5% improvement in the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) score in the simultaneous group, while the sequential group experienced 47.5% ± 15.8% improvement (p = 0.96). Moreover, a marked reduction in the levodopa-equivalent dose from preoperatively to postoperatively was similar in these 2 groups. The simultaneous bilateral procedure presented major advantages over the traditional sequential approach, with a shorter total operating time. CONCLUSIONS A simultaneous stereotactic approach significantly reduces the operation time in bilateral DBS procedures, resulting in decreased microrecording time, contributing to the optimization of functional

  17. Brain stem/brain stem occipital bone ratio and the four-line view in nuchal translucency images of fetuses with open spina bifida.

    Science.gov (United States)

    Iuculano, Ambra; Zoppi, Maria Angelica; Piras, Alessandra; Arras, Maurizio; Monni, Giovanni

    2014-09-10

    Abstract Objective: Brain stem depth/brain stem occipital bone distance (BS/BSOB ratio) and the four-line view, in images obtained for nuchal translucency (NT) screening in fetuses with open spina bifida (OSB). Methods: Single center, retrospective study based on the assessment of NT screening images of fetuses with OSB. A ratio between the BS depth and the BSOB distance was calculated (BS/BSOB ratio) and the four-line view observed, and the sensitivity for a BS/BSOB ratio superior/equal to 1, and for the lack of detection of the four-line view were calculated. Results: There were 17 cases of prenatal diagnosis OSB. In six cases, the suspicion on OSB was raised during NT screening, in six cases, the diagnosis was made before 20 weeks and in five cases during anomaly scan. The BS/BSOB ratio was superior/equal to 1 in all 17 cases, and three lines, were visualized in 15/17 images of the OSB cases, being the sensitivity 100% (95% CI, 81 to 100%) and 88% (95% CI, 65 to 96%). Conclusion: Assessment of BS/BSOB ratio and four-line view in NT images is feasible detecting affected by OSB with high sensitivity. The presence of associated anomalies or of an enlarged NT enhances the early detection.

  18. Cell Therapy in Parkinson's Disease: Host Brain Repair Machinery Gets a Boost From Stem Cell Grafts.

    Science.gov (United States)

    Napoli, Eleonora; Borlongan, Cesar V

    2017-06-01

    This commentary highlights the major findings and future research directions arising from the recent publication by Zuo and colleagues in Stem Cells 2017 (in press). Here, we discuss the novel observations that transplanted human neural stem cells can induce endogenous brain repair by specifically stimulating a host of regenerative processes in the neurogenic niche (i.e., subventricular zone [SVZ]) in an animal model of Parkinson's disease. That the identified therapeutic proteomes, neurotrophic factors, and anti-inflammatory cytokines in the SVZ may facilitate brain regeneration and behavioral recovery open a new venue of research for our understanding of the pathology and treatment of Parkinson's disease. Stem Cells 2017;35:1443-1445. © 2017 AlphaMed Press.

  19. A preliminary biomechanical study of a novel carbon-fibre hip implant versus standard metallic hip implants.

    Science.gov (United States)

    Bougherara, Habiba; Zdero, Rad; Dubov, Anton; Shah, Suraj; Khurshid, Shaheen; Schemitsch, Emil H

    2011-01-01

    Total hip arthroplasty is a widespread surgical approach for treating severe osteoarthritis of the human hip. Aseptic loosening of standard metallic hip implants due to stress shielding and bone loss has motivated the development of new materials for hip prostheses. Numerically, a three-dimensional finite element (FE) model that mimicked hip implants was used to compare a new hip stem to two commercially available implants. The hip implants simulated were a novel CF/PA12 carbon-fibre polyamide-based composite hip stem, the Exeter hip stem (Stryker, Mahwah, NJ, USA), and the Omnifit Eon (Stryker, Mahwah, NJ, USA). A virtual axial load of 3 kN was applied to the FE model. Strain and stress distributions were computed. Experimentally, the three hip stems had their distal portions rigidly mounted and had strain gauges placed along the surface at 3 medial and 3 lateral locations. Axial loads of 3 kN were applied. Measurements of axial stiffness and strain were taken and compared to FE analysis. The overall linear correlation between FE model versus experimental strains showed reasonable results for the lines-of-best-fit for the Composite (Pearson R(2)=0.69, slope=0.82), Exeter (Pearson R(2)=0.78, slope=0.59), and Omnifit (Pearson R(2)=0.66, slope=0.45), with some divergence for the most distal strain locations. From FE analysis, the von Mises stress range for the Composite stem was much lower than that in the Omnifit and Exeter implants by 200% and 45%, respectively. The preliminary experiments showed that the Composite stem stiffness (1982 N/mm) was lower than the metallic hip stem stiffnesses (Exeter, 2460 N/mm; Omnifit, 2543 N/mm). This is the first assessment of stress, strain, and stiffness of the CF/PA12 carbon-fibre hip stem compared to standard commercially-available devices. Copyright © 2010 IPEM. Published by Elsevier Ltd. All rights reserved.

  20. Neural stem cells encapsulated in a functionalized self-assembling peptide hydrogel for brain tissue engineering.

    Science.gov (United States)

    Cheng, Tzu-Yun; Chen, Ming-Hong; Chang, Wen-Han; Huang, Ming-Yuan; Wang, Tzu-Wei

    2013-03-01

    Brain injury is almost irreparable due to the poor regenerative capability of neural tissue. Nowadays, new therapeutic strategies have been focused on stem cell therapy and supplying an appropriate three dimensional (3D) matrix for the repair of injured brain tissue. In this study, we specifically linked laminin-derived IKVAV motif on the C-terminal to enrich self-assembling peptide RADA(16) as a functional peptide-based scaffold. Our purpose is providing a functional self-assembling peptide 3D hydrogel with encapsulated neural stem cells to enhance the reconstruction of the injured brain. The physiochemical properties reported that RADA(16)-IKVAV can self-assemble into nanofibrous morphology with bilayer β-sheet structure and become gelationed hydrogel with mechanical stiffness similar to brain tissue. The in vitro results showed that the extended IKVAV sequence can serve as a signal or guiding cue to direct the encapsulated neural stem cells (NSCs) adhesion and then towards neuronal differentiation. Animal study was conducted in a rat brain surgery model to demonstrate the damage in cerebral neocortex/neopallium loss. The results showed that the injected peptide solution immediately in situ formed the 3D hydrogel filling up the cavity and bridging the gaps. The histological analyses revealed the RADA(16)-IKVAV self-assembling peptide hydrogel not only enhanced survival of encapsulated NSCs but also reduced the formation of glial astrocytes. The peptide hydrogel with IKVAV extended motifs also showed the support of encapsulated NSCs in neuronal differentiation and the improvement in brain tissue regeneration after 6 weeks post-transplantation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Assessment of functional recovery after autologous implantation of neural progenitor cells for the treatment of traumatic brain injury

    International Nuclear Information System (INIS)

    Wu Xing; Zhang Dong; Zuo Zhuantao; Ge Feng; Zhu Jianhong; Zhou Liangfu

    2005-01-01

    Objective: To assess the functional recovery in the patients with traumatic brain injury (TBI) after autologous implantation of neural progenitor cells, and 7 counterparts with matched age, injury location and extent were chosen as the control. Methods: Neural progenitor cells were isolated from exposed brain tissue and propagated for 25 to 30 d, then implanted the autologous neural progenitor cells at seven points around the traumatic regions with MRI-stereotactic guiding device for 7 patients. All recruited patients underwent 18 F-fluorodeox-yglucose (FDG) PET imaging, function MRI (fMRI) and assessment of Glasgow outcome scale extended (GOSE) after operation for open brain trauma. The examinations were repeated one month after neural progenitor cell implantation and then repeated every 3 months during follow-up in the first year, and every 6 months in the second year. The same examinations were performed on untreated counterparts at similar intervals for avoiding deviations of spontaneous recovery. The data were analyzed with region of interest (ROI) and statistical parametric mapping (SPM). Results: At the third month of follow-up, mean tracer uptake in the damaged territory in implantation group increased significantly (P 18 F-FDG in the top of precentral gyrus was significantly increased in implantation group, and the metabolism of 18 F-FDG in the frontal lobe was significantly elevated postoperation according to paired SPM analysis. The activation in fMRI maps was seen in the motor cortex since the third month after implantation, whereas no active signals were detected before implantation or in control group. At the 6th month of follow-up, mean score of GOSE in the group of implantation was 6.63±0.52, whereas the mean score was 4.50 ±0.76 in control group (P 18 F-FDG uptake in the injured area was 3 months prior to the elevation of GOSE. Conclusions: The results of the study show that 18 F-FDG PET and fMRI both showed significantly increased neurological

  2. Brain mesenchymal stem cells: physiology and pathological implications.

    Science.gov (United States)

    Pombero, Ana; Garcia-Lopez, Raquel; Martinez, Salvador

    2016-06-01

    Mesenchymal stem cells (MSCs) are defined as progenitor cells that give rise to a number of unique, differentiated mesenchymal cell types. This concept has progressively evolved towards an all-encompassing concept including multipotent perivascular cells of almost any tissue. In central nervous system, pericytes are involved in blood-brain barrier, and angiogenesis and vascular tone regulation. They form the neurovascular unit (NVU) together with endothelial cells, astrocytes and neurons. This functional structure provides an optimal microenvironment for neural proliferation in the adult brain. Neurovascular niche include both diffusible signals and direct contact with endothelial and pericytes, which are a source of diffusible neurotrophic signals that affect neural precursors. Therefore, MSCs/pericyte properties such as differentiation capability, as well as immunoregulatory and paracrine effects make them a potential resource in regenerative medicine. © 2016 Japanese Society of Developmental Biologists.

  3. Comparison of Regenerative Tissue Quality following Matrix-Associated Cell Implantation Using Amplified Chondrocytes Compared to Synovium-Derived Stem Cells in a Rabbit Model for Cartilage Lesions

    DEFF Research Database (Denmark)

    Schmal, Hagen; Kowal, Justyna M; Kassem, Moustapha

    2018-01-01

    Known problems of the autologous chondrocyte implantation motivate the search for cellular alternatives. The aim of the study was to test the potential of synovium-derived stem cells (SMSC) to regenerate cartilage using a matrix-associated implantation. In an osteochondral defect model of the med......Known problems of the autologous chondrocyte implantation motivate the search for cellular alternatives. The aim of the study was to test the potential of synovium-derived stem cells (SMSC) to regenerate cartilage using a matrix-associated implantation. In an osteochondral defect model...... of the medial femoral condyle in a rabbit, a collagen membrane was seeded with either culture-expanded allogenic chondrocytes or SMSC and then transplanted into the lesion. A tailored piece synovium served as a control. Rabbit SMSC formed typical cartilage in vitro. Macroscopic evaluation of defect healing...... and the thickness of the regenerated tissue did not reveal a significant difference between the intervention groups. However, instantaneous and shear modulus, reflecting the biomechanical strength of the repair tissue, was superior in the implantation group using allogenic chondrocytes (p

  4. A stable and reproducible human blood-brain barrier model derived from hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Romeo Cecchelli

    Full Text Available The human blood brain barrier (BBB is a selective barrier formed by human brain endothelial cells (hBECs, which is important to ensure adequate neuronal function and protect the central nervous system (CNS from disease. The development of human in vitro BBB models is thus of utmost importance for drug discovery programs related to CNS diseases. Here, we describe a method to generate a human BBB model using cord blood-derived hematopoietic stem cells. The cells were initially differentiated into ECs followed by the induction of BBB properties by co-culture with pericytes. The brain-like endothelial cells (BLECs express tight junctions and transporters typically observed in brain endothelium and maintain expression of most in vivo BBB properties for at least 20 days. The model is very reproducible since it can be generated from stem cells isolated from different donors and in different laboratories, and could be used to predict CNS distribution of compounds in human. Finally, we provide evidence that Wnt/β-catenin signaling pathway mediates in part the BBB inductive properties of pericytes.

  5. Conductive Hearing Loss during Infancy: Effects on Later Auditory Brain Stem Electrophysiology.

    Science.gov (United States)

    Gunnarson, Adele D.; Finitzo, Terese

    1991-01-01

    Long-term effects on auditory electrophysiology from early fluctuating hearing loss were studied in 27 children, aged 5 to 7 years, who had been evaluated originally in infancy. Findings suggested that early fluctuating hearing loss disrupts later auditory brain stem electrophysiology. (Author/DB)

  6. Radiation and misonidazole in children with brain stem gliomas and supratentorial glioblastoma

    International Nuclear Information System (INIS)

    Bloom, H.J.G.; Bugden, R.D.

    1982-01-01

    In a series of 484 children with intracranial tumors referred to the Royal Marsden Hospital for radiotherapy, there were 47 (12%) examples of inoperable pontine and medullary tumors for which the 5-year survival rate was 17%. The limited local tumor mass in brain stem tumors, the absence of cerebro-spinal or distant metastases, and their often initial good but short-lived response to irradiation, all support the trial of a chemical radiosensitizing agent with which to try and achieve greater and more prolonged local control of the disease. Since the prognosis for cerebral hemisphere glioblastoma, which is relatively uncommon in children, is also extremely poor, such cases were included in this pilot study. The problems and possible risks associated with combined radiotherapy and a chemical radiosensitizer in children with brain tumors is discussed. So far, 8 children with brain stem tumors and 3 children with cerebral hemisphere gliomas heave been treated in this study. In addtion, data is also available on 3 children re-treated for incurrent medulloblastomas. Preliminary observations regarding experience with this small series will be reported including blood misonidazole levels, drug tolerance and the possible influence of anticonvulsants and steriods on toxicity

  7. Implanted, inductively-coupled, radiofrequency coils fabricated on flexible polymeric material: Application to in vivo rat brain MRI at 7 T

    International Nuclear Information System (INIS)

    Ginefri, J.C.; Poirier-Quinot, M.; Darrasse, L.; Rubin, A.; Tatoulian, M.; Woytasik, M.; Boumezbeur, F.; Djemai, B.; Lethimonnier, F.

    2012-01-01

    Combined with high-field MRI scanners, small implanted coils allow for high resolution imaging with locally improved SNR, as compared to external coils. Small flexible implantable coils dedicated to in vivo MRI of the rat brain at 7 T were developed. Based on the Multi-turn Transmission Line Resonator design, they were fabricated with a Teflon substrate using copper micro-molding process and a specific metal-polymer adhesion treatment. The implanted coils were made biocompatible by Polydimethylsiloxane (PDMS) encapsulation. The use of low loss tangent material achieves low dielectric losses within the substrate and the use of the PDMS layer reduces the parasitic coupling with the surrounding media. An implanted coil was implemented in a 7 T MRI system using inductive coupling and a dedicated external pick-up coil for signal transmission. In vivo images of the rat brain acquired with in plane resolution of (150 μm) 2 thanks to the implanted coil revealed high SNR near the coil, allowing for the visualization of fine cerebral structures. (authors)

  8. Mg ion implantation on SLA-treated titanium surface and its effects on the behavior of mesenchymal stem cell

    International Nuclear Information System (INIS)

    Kim, Beom-Su; Kim, Jin Seong; Park, Young Min; Choi, Bo-Young; Lee, Jun

    2013-01-01

    Magnesium (Mg) is one of the most important ions associated with bone osseointegration. The aim of this study was to evaluate the cellular effects of Mg implantation in titanium (Ti) surfaces treated with sand blast using large grit and acid etching (SLA). Mg ions were implanted into the surface via vacuum arc source ion implantation. The surface morphology, chemical properties, and the amount of Mg ion release were evaluated by scanning electron microscopy (SEM), Auger electron spectroscopy (AES), Rutherford backscattering spectroscopy (RBS), and inductively coupled plasma-optical emission spectrometer (ICP-OES). Human mesenchymal stem cells (hMSCs) were used to evaluate cellular parameters such as proliferation, cytotoxicity, and adhesion morphology by MTS assay, live/dead assay, and SEM. Furthermore, osteoblast differentiation was determined on the basis of alkaline phosphatase (ALP) activity and the degree of calcium accumulation. In the Mg ion-implanted disk, 2.3 × 10 16 ions/cm 2 was retained. However, after Mg ion implantation, the surface morphology did not change. Implanted Mg ions were rapidly released during the first 7 days in vitro. The MTS assay, live/dead assay, and SEM demonstrated increased cell attachment and growth on the Mg ion-implanted surface. In particular, Mg ion implantation increased the initial cell adhesion, and in an osteoblast differentiation assay, ALP activity and calcium accumulation. These findings suggest that Mg ion implantation using the plasma source ion implantation (PSII) technique may be useful for SLA-treated Ti dental implants to improve their osseointegration capacity. - Highlights: ► Mg ion was coated onto surface of SLA treated titanium via vacuum arc source ion implantation method. ► The morphological characteristics did not change after Mg ion implantation. ► Mg ion implanted SLA Ti is highly cytocompatible. ► Initial cell adhesion of MSCs is improved by Mg ion implantation. ► Mg ion implantation improved

  9. Diffusion Tensor Tractography Imaging in a Case of Acute Brain Stem Infarct

    Directory of Open Access Journals (Sweden)

    Nilgül Yardımcı

    2009-03-01

    Full Text Available Diffusion tensor tractography enables graphical reconstruction of the white matter pathways in the brain and quantitative study of white matter integrity. With this method virtual dissection of the living human brain can be performed. This technique has many potential clinical applications in neurological disorders, including the investigation of stroke. We present tractography findings of a patient that had an acute ischemic infarct in the brain stem. We aimed to report the disintegration of the white matter tracts at the infarct location in vivo, as well as the associated clinical symptoms. The current use of tractography in neurological disorders shows that it has the potential to improve our understanding of the damage and recovery process in diseases of the brain and spinal cord. From a clinical point of view tractography might be used to test new hypotheses, and to provide important new insights into the organization of the brain and the effects of brain disorders

  10. Listening to Brain Microcircuits for Interfacing With External World-Progress in Wireless Implantable Microelectronic Neuroengineering Devices: Experimental systems are described for electrical recording in the brain using multiple microelectrodes and short range implantable or wearable broadcasting units.

    Science.gov (United States)

    Nurmikko, Arto V; Donoghue, John P; Hochberg, Leigh R; Patterson, William R; Song, Yoon-Kyu; Bull, Christopher W; Borton, David A; Laiwalla, Farah; Park, Sunmee; Ming, Yin; Aceros, Juan

    2010-01-01

    Acquiring neural signals at high spatial and temporal resolution directly from brain microcircuits and decoding their activity to interpret commands and/or prior planning activity, such as motion of an arm or a leg, is a prime goal of modern neurotechnology. Its practical aims include assistive devices for subjects whose normal neural information pathways are not functioning due to physical damage or disease. On the fundamental side, researchers are striving to decipher the code of multiple neural microcircuits which collectively make up nature's amazing computing machine, the brain. By implanting biocompatible neural sensor probes directly into the brain, in the form of microelectrode arrays, it is now possible to extract information from interacting populations of neural cells with spatial and temporal resolution at the single cell level. With parallel advances in application of statistical and mathematical techniques tools for deciphering the neural code, extracted populations or correlated neurons, significant understanding has been achieved of those brain commands that control, e.g., the motion of an arm in a primate (monkey or a human subject). These developments are accelerating the work on neural prosthetics where brain derived signals may be employed to bypass, e.g., an injured spinal cord. One key element in achieving the goals for practical and versatile neural prostheses is the development of fully implantable wireless microelectronic "brain-interfaces" within the body, a point of special emphasis of this paper.

  11. In vivo bioluminescence imaging for prolonged survival of transplanted human neural stem cells using 3D biocompatible scaffold in corticectomized rat model.

    Directory of Open Access Journals (Sweden)

    Do Won Hwang

    Full Text Available Stem cell-based treatment of traumatic brain injury has been limited in its capacity to bring about complete functional recovery, because of the poor survival rate of the implanted stem cells. It is known that biocompatible biomaterials play a critical role in enhancing survival and proliferation of transplanted stem cells via provision of mechanical support. In this study, we noninvasively monitored in vivo behavior of implanted neural stem cells embedded within poly-l-lactic acid (PLLA scaffold, and showed that they survived over prolonged periods in corticectomized rat model. Corticectomized rat models were established by motor-cortex ablation of the rat. F3 cells expressing enhanced firefly luciferase (F3-effLuc were established through retroviral infection. The F3-effLuc within PLLA was monitored using IVIS-100 imaging system 7 days after corticectomized surgery. F3-effLuc within PLLA robustly adhered, and gradually increased luciferase signals of F3-effLuc within PLLA were detected in a day dependent manner. The implantation of F3-effLuc cells/PLLA complex into corticectomized rats showed longer-lasting luciferase activity than F3-effLuc cells alone. The bioluminescence signals from the PLLA-encapsulated cells were maintained for 14 days, compared with 8 days for the non-encapsulated cells. Immunostaining results revealed expression of the early neuronal marker, Tuj-1, in PLLA-F3-effLuc cells in the motor-cortex-ablated area. We observed noninvasively that the mechanical support by PLLA scaffold increased the survival of implanted neural stem cells in the corticectomized rat. The image-guided approach easily proved that scaffolds could provide supportive effect to implanted cells, increasing their viability in terms of enhancing therapeutic efficacy of stem-cell therapy.

  12. Nuclear Receptor TLX Regulates Cell Cycle Progression in Neural Stem Cells of the Developing Brain

    OpenAIRE

    Li, Wenwu; Sun, Guoqiang; Yang, Su; Qu, Qiuhao; Nakashima, Kinichi; Shi, Yanhong

    2007-01-01

    TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal ...

  13. VEGF-mediated angiogenesis stimulates neural stem cell proliferation and differentiation in the premature brain

    International Nuclear Information System (INIS)

    Sun, Jinqiao; Sha, Bin; Zhou, Wenhao; Yang, Yi

    2010-01-01

    This study investigated the effects of angiogenesis on the proliferation and differentiation of neural stem cells in the premature brain. We observed the changes in neurogenesis that followed the stimulation and inhibition of angiogenesis by altering vascular endothelial growth factor (VEGF) expression in a 3-day-old rat model. VEGF expression was overexpressed by adenovirus transfection and down-regulated by siRNA interference. Using immunofluorescence assays, Western blot analysis, and real-time PCR methods, we observed angiogenesis and the proliferation and differentiation of neural stem cells. Immunofluorescence assays showed that the number of vWF-positive areas peaked at day 7, and they were highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at every time point. The number of neural stem cells, neurons, astrocytes, and oligodendrocytes in the subventricular zone gradually increased over time in the VEGF up-regulation group. Among the three groups, the number of these cells was highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at the same time point. Western blot analysis and real-time PCR confirmed these results. These data suggest that angiogenesis may stimulate the proliferation of neural stem cells and differentiation into neurons, astrocytes, and oligodendrocytes in the premature brain.

  14. TGFβ lengthens the G1 phase of stem cells in aged mouse brain.

    Science.gov (United States)

    Daynac, Mathieu; Pineda, Jose R; Chicheportiche, Alexandra; Gauthier, Laurent R; Morizur, Lise; Boussin, François D; Mouthon, Marc-André

    2014-12-01

    Neurogenesis decreases during aging causing a progressive cognitive decline but it is still controversial whether proliferation defects in neurogenic niches result from a loss of neural stem cells or from an impairment of their progression through the cell cycle. Using an accurate fluorescence-activated cell sorting technique, we show that the pool of neural stem cells is maintained in the subventricular zone of middle-aged mice while they have a reduced proliferative potential eventually leading to the subsequent decrease of their progeny. In addition, we demonstrate that the G1 phase is lengthened during aging specifically in activated stem cells, but not in transit-amplifying cells, and directly impacts on neurogenesis. Finally, we report that inhibition of TGFβ signaling restores cell cycle progression defects in stem cells. Our data highlight the significance of cell cycle dysregulation in stem cells in the aged brain and provide an attractive foundation for the development of anti-TGFβ regenerative therapies based on stimulating endogenous neural stem cells. © 2014 AlphaMed Press.

  15. Implant Materials Generate Different Peri-implant Inflammatory Factors

    OpenAIRE

    Olivares-Navarrete, Rene; Hyzy, Sharon L.; Slosar, Paul J.; Schneider, Jennifer M.; Schwartz, Zvi; Boyan, Barbara D.

    2015-01-01

    Study Design. An in vitro study examining factors produced by human mesenchymal stem cells on spine implant materials. Objective. The aim of this study was to examine whether the inflammatory microenvironment generated by cells on titanium-aluminum-vanadium (Ti-alloy, TiAlV) surfaces is affected by surface microtexture and whether it differs from that generated on poly-ether-ether-ketone (PEEK). Summary of Background Data. Histologically, implants fabricated from PEEK have a fibrous connectiv...

  16. Regional distribution of TL-201 in the brain and spinal cord after injection into the cerebrospinal fluid: Imaging of brain tumors

    International Nuclear Information System (INIS)

    Woo, D.V.; Rubertone, J.; Vincent, S.; Brady, L.W. Jr.

    1986-01-01

    Radiotracers are typically employed to evaluate the brain ventricular space; however, there are no agents designed to be taken up into specific neuronal regions after injection into the cerebrospinal fluids (CSF). The authors report studies in which T1-201 was stereotaxically administered into the lateral or fourth ventricles of Sprague-Dawley rats. Brains were removed (n = 42) 2-6 hours after injection and sectioned for apposition to autoradiographic film. Specific uptake was observed in active neurons of the diencephalon, mesencephalon, cerebellum, brain stem, and spinal gray matter. Astrocytoma cell implants into the caudate nucleus of Sprague-Dawley rats induced histologically confirmed brain tumors (n = 5). Significant localization of T1-201 was observed in the tumor 4 hours after injection into the lateral ventricle. These findings suggest that T1-201 may be useful for delineating specific neuronal function via CSF circulation and for imaging actively growing brain tumors

  17. Homing and Tracking of Iron Oxide Labelled Mesenchymal Stem Cells After Infusion in Traumatic Brain Injury Mice: a Longitudinal In Vivo MRI Study.

    Science.gov (United States)

    Mishra, Sushanta Kumar; Khushu, Subash; Singh, Ajay K; Gangenahalli, Gurudutta

    2018-06-17

    Stem cells transplantation has emerged as a promising alternative therapeutic due to its potency at injury site. The need to monitor and non-invasively track the infused stem cells is a significant challenge in the development of regenerative medicine. Thus, in vivo tracking to monitor infused stem cells is especially vital. In this manuscript, we have described an effective in vitro labelling method of MSCs, a serial in vivo tracking of implanted stem cells at traumatic brain injury (TBI) site through 7 T magnetic resonance imaging (MRI). Proper homing of infused MSCs was carried out at different time points using histological analysis and Prussian blue staining. Longitudinal in vivo tracking of infused MSCs were performed up to 21 days in different groups through MRI using relaxometry technique. Results demonstrated that MSCs incubated with iron oxide-poly-L-lysine complex (IO-PLL) at a ratio of 50:1.5 μg/ml and a time period of 6 h was optimised to increase labelling efficiency. T2*-weighted images and relaxation study demonstrated a significant signal loss and effective decrease in transverse relaxation time on day-3 at injury site after systemic transplantation, revealed maximum number of stem cells homing to the lesion area. MRI results further correlate with histological and Prussian blue staining in different time periods. Decrease in negative signal and increase in relaxation times were observed after day-14, may indicate damage tissue replacement with healthy tissue. MSCs tracking with synthesized negative contrast agent represent a great advantage during both in vitro and in vivo analysis. The proposed absolute bias correction based relaxometry analysis could be extrapolated for stem cell tracking and therapies in various neurodegenerative diseases.

  18. Store-Operated Calcium Entries Control Neural Stem Cell Self-Renewal in the Adult Brain Subventricular Zone.

    Science.gov (United States)

    Domenichini, Florence; Terrié, Elodie; Arnault, Patricia; Harnois, Thomas; Magaud, Christophe; Bois, Patrick; Constantin, Bruno; Coronas, Valérie

    2018-05-01

    The subventricular zone (SVZ) is the major stem cell niche in the brain of adult mammals. Within this region, neural stem cells (NSC) proliferate, self-renew and give birth to neurons and glial cells. Previous studies underlined enrichment in calcium signaling-related transcripts in adult NSC. Because of their ability to mobilize sustained calcium influxes in response to a wide range of extracellular factors, store-operated channels (SOC) appear to be, among calcium channels, relevant candidates to induce calcium signaling in NSC whose cellular activities are continuously adapted to physiological signals from the microenvironment. By Reverse Transcription Polymerase Chain Reaction (RT-PCR), Western blotting and immunocytochemistry experiments, we demonstrate that SVZ cells express molecular actors known to build up SOC, namely transient receptor potential canonical 1 (TRPC1) and Orai1, as well as their activator stromal interaction molecule 1 (STIM1). Calcium imaging reveals that SVZ cells display store-operated calcium entries. Pharmacological blockade of SOC with SKF-96365 or YM-58483 (also called BTP2) decreases proliferation, impairs self-renewal by shifting the type of SVZ stem cell division from symmetric proliferative to asymmetric, thereby reducing the stem cell population. Brain section immunostainings show that TRPC1, Orai1, and STIM1 are expressed in vivo, in SOX2-positive SVZ NSC. Injection of SKF-96365 in brain lateral ventricle diminishes SVZ cell proliferation and reduces the ability of SVZ cells to form neurospheres in vitro. The present study combining in vitro and in vivo approaches uncovers a major role for SOC in the control of SVZ NSC population and opens new fields of investigation for stem cell biology in health and disease. Stem Cells 2018;36:761-774. © AlphaMed Press 2018.

  19. Age and Gender Effects On Auditory Brain Stem Response (ABR

    Directory of Open Access Journals (Sweden)

    Yones Lotfi

    2012-10-01

    Full Text Available Objectives: Auditory Brain Stem Response (ABR is a result of eight nerve and brain stem nuclei stimulation. Several factors may affect the latencies, interpeak latencies and amplitudes in ABR especially sex and age. In this study, age and sex influence on ABR were studied. Methods: This study was performed on 120 cases (60 males and 60 females at Akhavan rehabilitation center of university of welfare and rehabilitation sciences, Tehran, Iran. Cases were divided in three age groups: 18-30, 31-50 and 51-70 years old. Each age group consists of 20 males and 20 females. Age and sex influences on absolute latency of wave I and V, and IPL of I-V were examined. Results: Independent t test showed that females have significantly shorter latency of wave I, V, and IPL I-V latency (P<0.001 than males. Two way ANOVA showed that latency of wave I, V and IPL I-V in 51-70 years old group was significantly higher than 18-30 and 31-50 years old groups (P<0.001 Discussion: According to the results of present study and similar studies, in clinical practice, different norms for older adults and both genders should be established.

  20. Stereotactic iodine-125 brachytherapy for brain tumors: temporary versus permanent implantation

    Directory of Open Access Journals (Sweden)

    Ruge Maximilian I

    2012-06-01

    Full Text Available Abstract Stereotactic brachytherapy (SBT has been described in several publications as an effective, minimal invasive and safe highly focal treatment option in selected patients with well circumscribed brain tumors 40 cGy/h in combination with adjuvant external beam radiation and/or chemotherapy for the treatment of malignant gliomas and metastases resulted in increased rates of radiation induced adverse tissue changes requiring surgical intervention. Vice versa, such effects have been only minimally observed in numerous studies applying low dose rate (LDR regiments (3–8 cGy/h for low grade gliomas, metastases and other rare indications. Besides these observations, there are, however, no data available directly comparing the long term incidences of tissue changes after HDR and LDR and there is, furthermore, no evidence regarding a difference between temporary or permanent LDR implantation schemes. Thus, recommendations for effective and safe implantation schemes have to be investigated and compared in future studies.

  1. Prognostic factors and therapeutic options of radiotherapy in pediatric brain stem gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yu-Ming; Shiau, Cheng-Ying; Wong, Tai-Tong; Wang, Ling-Wei; Wu, Le-Jung; Chi, Kwan-Hwa; Chen, Kuang Y.; Yen, Sang-Hue [Veterans General Hospital-Taipei, Taipei, Taiwan (China)

    1998-08-01

    A retrospective analysis was made to clarify the relationship between prognosis, radiation dose and survival of brain stem gliomas. From 1983 to 1995, 22 children with brain stem tumors were treated by radiotherapy in the Veterans General Hospital-Taipei. Twelve patients had pathology proof and the remainder were diagnosed by computerized tomography and/or magnetic resonance imaging. Seven patients had postoperative radiotherapy. Fifteen patients had radiotherapy as primary management, five of whom had adjuvant chemotherapy. All patients received 4000-7060 cGy, either in conventional daily or hyperfractionated twice daily radiotherapy. Survival from date of diagnosis was calculated by the Kaplan-Meier method. Univariate analyses and multivariate analyses were calculated by the log rank test and the Cox proportional hazard model, respectively. Most patients showed improvement following treatment. The overall 2-year survival rate was 55.5% with a median survival of 27.1 months. Two-year survival for patients with primary management of operation and radiotherapy (n=7), radiotherapy alone (n=10) and radiotherapy with adjuvant chemotherapy (n=5) were 66.7, 50 and 53.3%, respectively. In univariate analysis, the study revealed that the growth pattern of tumors and the simultaneous presence of cranial neuropathy and long tract sign were significant prognostic factors (P=0.017 and 0.036). A trend of better outcome with radiation dose >6600 cGy and the hyperfractionation scheme was also noted in our study (P=0.0573 and 0.0615). However, only the hyperfractionation scheme showed significance in multivariate analyses (P=0.0355). Survival was not significantly affected by age, gender or method of diagnosis. Radiotherapy appears to be an effective treatment modality of brain stem tumors. Patients with both cranial neuropathy and long tract signs had a poorer outcome. Hyperfractionated radiotherapy may give better local control and lead to better survival. (author)

  2. Prognostic factors and therapeutic options of radiotherapy in pediatric brain stem gliomas

    International Nuclear Information System (INIS)

    Liu, Yu-Ming; Shiau, Cheng-Ying; Wong, Tai-Tong; Wang, Ling-Wei; Wu, Le-Jung; Chi, Kwan-Hwa; Chen, Kuang Y.; Yen, Sang-Hue

    1998-01-01

    A retrospective analysis was made to clarify the relationship between prognosis, radiation dose and survival of brain stem gliomas. From 1983 to 1995, 22 children with brain stem tumors were treated by radiotherapy in the Veterans General Hospital-Taipei. Twelve patients had pathology proof and the remainder were diagnosed by computerized tomography and/or magnetic resonance imaging. Seven patients had postoperative radiotherapy. Fifteen patients had radiotherapy as primary management, five of whom had adjuvant chemotherapy. All patients received 4000-7060 cGy, either in conventional daily or hyperfractionated twice daily radiotherapy. Survival from date of diagnosis was calculated by the Kaplan-Meier method. Univariate analyses and multivariate analyses were calculated by the log rank test and the Cox proportional hazard model, respectively. Most patients showed improvement following treatment. The overall 2-year survival rate was 55.5% with a median survival of 27.1 months. Two-year survival for patients with primary management of operation and radiotherapy (n=7), radiotherapy alone (n=10) and radiotherapy with adjuvant chemotherapy (n=5) were 66.7, 50 and 53.3%, respectively. In univariate analysis, the study revealed that the growth pattern of tumors and the simultaneous presence of cranial neuropathy and long tract sign were significant prognostic factors (P=0.017 and 0.036). A trend of better outcome with radiation dose >6600 cGy and the hyperfractionation scheme was also noted in our study (P=0.0573 and 0.0615). However, only the hyperfractionation scheme showed significance in multivariate analyses (P=0.0355). Survival was not significantly affected by age, gender or method of diagnosis. Radiotherapy appears to be an effective treatment modality of brain stem tumors. Patients with both cranial neuropathy and long tract signs had a poorer outcome. Hyperfractionated radiotherapy may give better local control and lead to better survival. (author)

  3. Regional brain stem atrophy in idiopathic Parkinson's disease detected by anatomical MRI.

    Directory of Open Access Journals (Sweden)

    Thomas Jubault

    Full Text Available Idiopathic Parkinson's disease (PD is a neurodegenerative disorder characterized by the dysfunction of dopaminergic dependent cortico-basal ganglia loops and diagnosed on the basis of motor symptoms (tremors and/or rigidity and bradykinesia. Post-mortem studies tend to show that the destruction of dopaminergic neurons in the substantia nigra constitutes an intermediate step in a broader neurodegenerative process rather than a unique feature of Parkinson's disease, as a consistent pattern of progression would exist, originating from the medulla oblongata/pontine tegmentum. To date, neuroimaging techniques have been unable to characterize the pre-symptomatic stages of PD. However, if such a regular neurodegenerative pattern were to exist, consistent damages would be found in the brain stem, even at early stages of the disease. We recruited 23 PD patients at Hoenn and Yahr stages I to II of the disease and 18 healthy controls (HC matched for age. T1-weighted anatomical scans were acquired (MPRAGE, 1 mm3 resolution and analyzed using an optimized VBM protocol to detect white and grey matter volume reduction without spatial a priori. When the HC group was compared to the PD group, a single cluster exhibited statistical difference (p<0.05 corrected for false detection rate, 4287 mm3 in the brain stem, between the pons and the medulla oblongata. The present study provides in-vivo evidence that brain stem damage may be the first identifiable stage of PD neuropathology, and that the identification of this consistent damage along with other factors could help with earlier diagnosis in the future. This damage could also explain some non-motor symptoms in PD that often precede diagnosis, such as autonomic dysfunction and sleep disorders.

  4. Preventive sparing of spinal cord and brain stem in the initial irradiation of locally advanced head and neck cancers.

    Science.gov (United States)

    Farace, Paolo; Piras, Sara; Porru, Sergio; Massazza, Federica; Fadda, Giuseppina; Solla, Ignazio; Piras, Denise; Deidda, Maria Assunta; Amichetti, Maurizio; Possanzini, Marco

    2014-01-06

    Since reirradiation in recurrent head and neck patients is limited by previous treatment, a marked reduction of maximum doses to spinal cord and brain stem was investigated in the initial irradiation of stage III/IV head and neck cancers. Eighteen patients were planned by simultaneous integrated boost, prescribing 69.3 Gy to PTV1 and 56.1 Gy to PTV2. Nine 6 MV coplanar photon beams at equispaced gantry angles were chosen for each patient. Step-and-shoot IMRT was calculated by direct machine parameter optimization, with the maximum number of segments limited to 80. In the standard plan, optimization considered organs at risk (OAR), dose conformity, maximum dose < 45 Gy to spinal cord and < 50 Gy to brain stem. In the sparing plans, a marked reduction to spinal cord and brain stem were investigated, with/without changes in dose conformity. In the sparing plans, the maximum doses to spinal cord and brain stem were reduced from the initial values (43.5 ± 2.2 Gy and 36.7 ± 14.0 Gy), without significant changes on the other OARs. A marked difference (-15.9 ± 1.9 Gy and -10.1 ± 5.7 Gy) was obtained at the expense of a small difference (-1.3% ± 0.9%) from initial PTV195% coverage (96.6% ± 0.9%). Similar difference (-15.7 ± 2.2 Gy and -10.2 ± 6.1 Gy) was obtained compromising dose conformity, but unaffecting PTV195% and with negligible decrease in PTV295% (-0.3% ± 0.3% from the initial 98.3% ± 0.8%). A marked spinal cord and brain stem preventive sparing was feasible at the expense of a decrease in dose conformity or slightly compromising target coverage. A sparing should be recommended in highly recurrent tumors, to make potential reirradiation safer.

  5. Effects of atelocollagen on neural stem cell function and its migrating capacity into brain in psychiatric disease model.

    Science.gov (United States)

    Yoshinaga, Toshihiro; Hashimoto, Eri; Ukai, Wataru; Ishii, Takao; Shirasaka, Tomohiro; Kigawa, Yoshiyasu; Tateno, Masaru; Kaneta, Hiroo; Watanabe, Kimihiko; Igarashi, Takeshi; Kobayashi, Seiju; Sohma, Hitoshi; Kato, Tadafumi; Saito, Toshikazu

    2013-10-01

    Stem cell therapy is well proposed as a potential method for the improvement of neurodegenerative damage in the brain. Among several different procedures to reach the cells into the injured lesion, the intravenous (IV) injection has benefit as a minimally invasive approach. However, for the brain disease, prompt development of the effective treatment way of cellular biodistribution of stem cells into the brain after IV injection is needed. Atelocollagen has been used as an adjunctive material in a gene, drug and cell delivery system because of its extremely low antigenicity and bioabsorbability to protect these transplants from intrabody environment. However, there is little work about the direct effect of atelocollagen on stem cells, we examined the functional change of survival, proliferation, migration and differentiation of cultured neural stem cells (NSCs) induced by atelocollagen in vitro. By 72-h treatment 0.01-0.05% atelocollagen showed no significant effects on survival, proliferation and migration of NSCs, while 0.03-0.05% atelocollagen induced significant reduction of neuronal differentiation and increase of astrocytic differentiation. Furthermore, IV treated NSCs complexed with atelocollagen (0.02%) could effectively migrate into the brain rather than NSC treated alone using chronic alcohol binge model rat. These experiments suggested that high dose of atelocollagen exerts direct influence on NSC function but under 0.03% of atelocollagen induces beneficial effect on regenerative approach of IV administration of NSCs for CNS disease.

  6. Diffusion tensor imaging for nerve fiber bundles in the brain stem and spinocerebellar degeneration

    International Nuclear Information System (INIS)

    Honma, Tsuguo

    2009-01-01

    Diffusion tensor imaging (DTI) can create an image of the anisotropic nature of diffusion and express it quantitatively. Nerve fibers have a large anisotropic diffusion, and it is possible to obtain images of the nerve fiber bundle. The purpose of this study is to observe the nerve fiber bundles in the brain stem using DTI and study its potential for diagnosing the type of spinocerebellar degeneration (SCD). Fractional anisotropy (FA) maps and 3D-tractography images were obtained for 41 subjects with no brain stem abnormalities. We created an apparent diffusion coefficient (ADC) map and an FA map using DTI for 16 subjects in the disease group (11 with hereditary SCD and 5 with non-hereditary SCD) and 25 in the control group. The diffusion value of the pons and middle cerebellar peduncle was measured using ADC, and the degree of anisotropic diffusion was measured using FA. The pyramidal tract, superior cerebellar peduncle, and inferior cerebellar peduncle were clearly demonstrated for all cases. ADC for the middle cerebellar peduncle in spinocerebellar ataxin (SCA)1 was significantly higher, similar to that for the pons in dentatorubro-pallidoluysian atrophy (DRPLA). In MSA-C, ADC for both the pons and middle cerebellar peduncle was significantly elevated and FA was significantly decreased. There were no significant changes in SCA3. We could observe the nerve fiber bundles in the brain stem using DTI. FA and ADC measurements with DTI can aid in diagnosing the type of SCD. (author)

  7. Bioceramic inlays do not improve mechanical incorporation of grit-blasted titanium stems in the proximal sheep femur.

    Science.gov (United States)

    Keränen, Pauli; Koort, Jyri; Itälä, Ari; Ylänen, Heimo; Dalstra, Michel; Hupa, Mikko; Kommonen, Bertel; Aro, Hannu T

    2010-03-15

    The aim of the present study was to determine, if bioactive glass (BG) surface inlays improve osseointegration of titanium implants in the proximal femur of adult sheep. In simulation of uncemented primary stems (nine animals), only the proximal part of the implants was grit-blasted and three surface slots of the grit-blasted region were filled with sintered BG microspheres. Primary stems were implanted using press-fit technique. In revision stem simulation (eight animals), grit-blasting was extended over the whole implant and seven perforating holes of the stem were filled by sintered BG granules. Revision stems were implanted with a mixture of autogenous bone graft and BG granules. Comparison with solid partially or fully grit-blasted control stems implanted in the contralateral femurs was performed in the primary and revision stem experiments at 12 and 25 weeks, respectively. Implant incorporation was evaluated by torsional failure testing and histomorphometry. Only one-third of the primary stems anchored mechanically to bone. The revision stems incorporated better and the BG inlays of the revision stems showed ingrowth of new bone. However, there were no significant differences in the torsional failure loads between the stems with BG inlays and the control stems. In conclusion, surface BG inlays gave no measurable advantage in mechanical incorporation of grit-blasted titanium implants. Overall, the proximal sheep femur, characterized by minimal amount of cancellous bone and the presence of adipocytic bone marrow, seemed to present compromised bone healing conditions. (c) 2009 Wiley Periodicals, Inc.

  8. [Abscess at the implant site following apical parodontitis. Hardware-related complications of deep brain stimulation].

    Science.gov (United States)

    Sixel-Döring, F; Trenkwalder, C; Kappus, C; Hellwig, D

    2006-08-01

    Deep brain stimulation of the subthalamic nucleus is an important treatment option for advanced stages of idiopathic Parkinson's disease, leading to significant improvement of motor symptoms in suited patients. Hardware-related complications such as technical malfunction, skin erosion, and infections however cause patient discomfort and additional expense. The patient presented here suffered a putrid infection of the impulse generator site following only local dental treatment of apical parodontitis. Therefore, prophylactic systemic antibiotic treatment is recommended for patients with implanted deep brain stimulation devices in case of operations, dental procedures, or infectious disease.

  9. Oral Implant-Prostheses: New Teeth for a Brighter Brain.

    Directory of Open Access Journals (Sweden)

    Vincenzo De Cicco

    Full Text Available Several studies have demonstrated that chewing can be regarded as a preventive measure for cognitive impairment, whereas masticatory deficiency, associated with soft-diet feeding, is a risk factor for the development of dementia. At present the link between orofacial sensorimotor activity and cognitive functions is unknown. In subjects with unilateral molar loss we have shown asymmetries in both pupil size and masticatory muscles electromyographic (EMG activity during clenching: the molar less side was characterized by a lower EMG activity and a smaller pupil. Since implant-prostheses, greatly reduced both the asymmetry in EMG activity and in pupil's size, trigeminal unbalance, leading to unbalance in the activity of the Locus Coeruleus (LC, may be responsible for the pupil's asymmetry. According to the findings obtained in animal models, we propose that the different activity of the right and left LC may induce an asymmetry in brain activity, thus leading to cognitive impairment. According to this hypothesis, prostheses improved the performance in a complex sensorimotor task and increased the mydriasis associated with haptic tasks. In conclusion, the present study indicates that the implant-prosthesis therapy, which reduces the unbalance of trigeminal proprioceptive afferents and the asymmetry in pupil's size, may improve arousal, boosting performance in a complex sensorimotor task.

  10. Chronic multisite brain recordings from a totally implantable bidirectional neural interface: experience in 5 patients with Parkinson's disease.

    Science.gov (United States)

    Swann, Nicole C; de Hemptinne, Coralie; Miocinovic, Svjetlana; Qasim, Salman; Ostrem, Jill L; Galifianakis, Nicholas B; Luciano, Marta San; Wang, Sarah S; Ziman, Nathan; Taylor, Robin; Starr, Philip A

    2018-02-01

    OBJECTIVE Dysfunction of distributed neural networks underlies many brain disorders. The development of neuromodulation therapies depends on a better understanding of these networks. Invasive human brain recordings have a favorable temporal and spatial resolution for the analysis of network phenomena but have generally been limited to acute intraoperative recording or short-term recording through temporarily externalized leads. Here, the authors describe their initial experience with an investigational, first-generation, totally implantable, bidirectional neural interface that allows both continuous therapeutic stimulation and recording of field potentials at multiple sites in a neural network. METHODS Under a physician-sponsored US Food and Drug Administration investigational device exemption, 5 patients with Parkinson's disease were implanted with the Activa PC+S system (Medtronic Inc.). The device was attached to a quadripolar lead placed in the subdural space over motor cortex, for electrocorticography potential recordings, and to a quadripolar lead in the subthalamic nucleus (STN), for both therapeutic stimulation and recording of local field potentials. Recordings from the brain of each patient were performed at multiple time points over a 1-year period. RESULTS There were no serious surgical complications or interruptions in deep brain stimulation therapy. Signals in both the cortex and the STN were relatively stable over time, despite a gradual increase in electrode impedance. Canonical movement-related changes in specific frequency bands in the motor cortex were identified in most but not all recordings. CONCLUSIONS The acquisition of chronic multisite field potentials in humans is feasible. The device performance characteristics described here may inform the design of the next generation of totally implantable neural interfaces. This research tool provides a platform for translating discoveries in brain network dynamics to improved neurostimulation

  11. Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

    Science.gov (United States)

    Anselmi, L; Toti, L; Bove, C; Travagli, R A

    2017-11-01

    Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1 ) assess the gastric effects of brain stem DA application, 2 ) identify the DA receptor subtype, and, 3 ) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility. NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway. Copyright © 2017 the American Physiological Society.

  12. A low power flash-FPGA based brain implant micro-system of PID control.

    Science.gov (United States)

    Lijuan Xia; Fattah, Nabeel; Soltan, Ahmed; Jackson, Andrew; Chester, Graeme; Degenaar, Patrick

    2017-07-01

    In this paper, we demonstrate that a low power flash FPGA based micro-system can provide a low power programmable interface for closed-loop brain implant inter- faces. The proposed micro-system receives recording local field potential (LFP) signals from an implanted probe, performs closed-loop control using a first order control system, then converts the signal into an optogenetic control stimulus pattern. Stimulus can be implemented through optoelectronic probes. The long term target is for both fundamental neuroscience applications and for clinical use in treating epilepsy. Utilizing our device, closed-loop processing consumes only 14nJ of power per PID cycle compared to 1.52μJ per cycle for a micro-controller implementation. Compared to an application specific digital integrated circuit, flash FPGA's are inherently programmable.

  13. Robotics, stem cells, and brain-computer interfaces in rehabilitation and recovery from stroke: updates and advances.

    Science.gov (United States)

    Boninger, Michael L; Wechsler, Lawrence R; Stein, Joel

    2014-11-01

    The aim of this study was to describe the current state and latest advances in robotics, stem cells, and brain-computer interfaces in rehabilitation and recovery for stroke. The authors of this summary recently reviewed this work as part of a national presentation. The article represents the information included in each area. Each area has seen great advances and challenges as products move to market and experiments are ongoing. Robotics, stem cells, and brain-computer interfaces all have tremendous potential to reduce disability and lead to better outcomes for patients with stroke. Continued research and investment will be needed as the field moves forward. With this investment, the potential for recovery of function is likely substantial.

  14. Induced hemocompatibility and bone formation as biological scaffold for cell therapy implant

    Directory of Open Access Journals (Sweden)

    Keng-Liang Ou

    2016-06-01

    Full Text Available Although stem cells can become almost any type of specialized cell in the human body and may have the potential to generate replacement cells for tissues and organs, the transplantation of these cells are hindered by immune rejection and teratoma formation. However, scientists have found a promising solution for these problems-they have discovered the ability to isolate stem cells from a patient’s umbilical cord blood or bone marrow. Even more recently, small stem cells, such as spore-like stem cells, Blastomere-Like Stem Cells (BLSCs, and Very-Small Embryonic-Like stem cells (VSELs isolated directly from the peripheral blood have beeninvestigated as a novel approach to stem cell therapy as they can be isolated directly from the peripheral blood. A newly-discovered population of multipotent stem cells in this class has been dubbed StemBios (SB cells. The potential therapeutic uses of such stem cells have been explored in many ways, one of which includes dental remodeling and construction. Using adult stem cells, scientists have engineered and cultivated teeth in mice that may one day be used for human implantation.It follows that such regeneration may be possible, to a certain degree, in human patients as well. This idea leads to the present study on the effect of SB cell therapy on early osseointegrationof dental implants. Titanium (Ti dental implants have been proven to be a reliable and predictable treatment for restoration of edentulous regions. The osseointegration process can be described in two stages: primary stability (mechanical stability and secondary stability (biological stability. The mechanical stabilization of the implant reflects the interaction between the bone density and the features of the implant designs and can be determined after implant insertion. Alternatively,the biological stabilization of the implant is a physiologic healing process. It is couple to the biological interaction between the external surface of the

  15. [Distribution of human enterovirus 71 in brainstem of infants with brain stem encephalitis and infection mechanism].

    Science.gov (United States)

    Hao, Bo; Gao, Di; Tang, Da-Wei; Wang, Xiao-Guang; Liu, Shui-Ping; Kong, Xiao-Ping; Liu, Chao; Huang, Jing-Lu; Bi, Qi-Ming; Quan, Li; Luo, Bin

    2012-04-01

    To explore the mechanism that how human enterovirus 71 (EV71) invades the brainstem and how intercellular adhesion molecules-1 (ICAM-1) participates by analyzing the expression and distribution of human EV71, and ICAM-1 in brainstem of infants with brain stem encephalitis. Twenty-two brainstem of infants with brain stem encephalitis were collected as the experimental group and 10 brainstems of fatal congenital heart disease were selected as the control group. The sections with perivascular cuffings were selected to observe EV71-VP1 expression by immunohistochemistry method and ICAM-1 expression was detected for the sections with EV71-VP1 positive expression. The staining image analysis and statistics analysis were performed. The experiment and control groups were compared. (1) EV71-VP1 positive cells in the experimental group were mainly astrocytes in brainstem with nigger-brown particles, and the control group was negative. (2) ICAM-1 positive cells showed nigger-brown. The expression in inflammatory cells (around blood vessels of brain stem and in glial nodules) and gliocytes increased. The results showed statistical difference comparing with control group (P diagnose fatal EV71 infection in infants. EV71 can invade the brainstem via hematogenous route. ICAM-1 may play an important role in the pathogenic process.

  16. Maternal Inflammation Contributes to Brain Overgrowth and Autism-Associated Behaviors through Altered Redox Signaling in Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Janel E. Le Belle

    2014-11-01

    Full Text Available A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species.

  17. Human umbilical cord blood-derived stem cells and brain-derived neurotrophic factor protect injured optic nerve: viscoelasticity characterization

    Directory of Open Access Journals (Sweden)

    Xue-man Lv

    2016-01-01

    Full Text Available The optic nerve is a viscoelastic solid-like biomaterial. Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury. We hypothesized that stress relaxation and creep properties of the optic nerve change after injury. More-over, human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal. To validate this hypothesis, a rabbit model of optic nerve injury was established using a clamp approach. At 7 days after injury, the vitreous body re-ceived a one-time injection of 50 µg human brain-derived neurotrophic factor or 1 × 106 human umbilical cord blood-derived stem cells. At 30 days after injury, stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly, with patho-logical changes in the injured optic nerve also noticeably improved. These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves, and thereby contributes to nerve recovery.

  18. High-resolution anatomy of the human brain stem using 7-T MRI: improved detection of inner structures and nerves?

    Energy Technology Data Exchange (ETDEWEB)

    Gizewski, Elke R. [Medical University Innsbruck, Department of Neuroradiology, Innsbruck (Austria); Maderwald, Stefan [University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Linn, Jennifer; Bochmann, Katja [LMU Munich, Department of Neuroradiology, Munich (Germany); Dassinger, Benjamin [Medical University Innsbruck, Department of Neuroradiology, Innsbruck (Austria); Justus-Liebig-University Giessen, Department of Neuroradiology, Giessen (Germany); Forsting, Michael [University Hospital, University Duisburg-Essen, Departments of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Ladd, Mark E. [University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); University Hospital, University Duisburg-Essen, Departments of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany)

    2014-03-15

    The purpose of this paper is to assess the value of 7 Tesla (7 T) MRI for the depiction of brain stem and cranial nerve (CN) anatomy. Six volunteers were examined at 7 T using high-resolution SWI, MPRAGE, MP2RAGE, 3D SPACE T2, T2, and PD images to establish scanning parameters targeted at optimizing spatial resolution. Direct comparisons between 3 and 7 T were performed in two additional subjects using the finalized sequences (3 T: T2, PD, MPRAGE, SWAN; 7 T: 3D T2, MPRAGE, SWI, MP2RAGE). Artifacts and the depiction of structures were evaluated by two neuroradiologists using a standardized score sheet. Sequences could be established for high-resolution 7 T imaging even in caudal cranial areas. High in-plane resolution T2, PD, and SWI images provided depiction of inner brain stem structures such as pons fibers, raphe, reticular formation, nerve roots, and periaqueductal gray. MPRAGE and MP2RAGE provided clear depiction of the CNs. 3D T2 images improved depiction of inner brain structure in comparison to T2 images at 3 T. Although the 7-T SWI sequence provided improved contrast to some inner structures, extended areas were influenced by artifacts due to image disturbances from susceptibility differences. Seven-tesla imaging of basal brain areas is feasible and might have significant impact on detection and diagnosis in patients with specific diseases, e.g., trigeminal pain related to affection of the nerve root. Some inner brain stem structures can be depicted at 3 T, but certain sequences at 7 T, in particular 3D SPACE T2, are superior in producing anatomical in vivo images of deep brain stem structures. (orig.)

  19. High-resolution anatomy of the human brain stem using 7-T MRI: improved detection of inner structures and nerves?

    International Nuclear Information System (INIS)

    Gizewski, Elke R.; Maderwald, Stefan; Linn, Jennifer; Bochmann, Katja; Dassinger, Benjamin; Forsting, Michael; Ladd, Mark E.

    2014-01-01

    The purpose of this paper is to assess the value of 7 Tesla (7 T) MRI for the depiction of brain stem and cranial nerve (CN) anatomy. Six volunteers were examined at 7 T using high-resolution SWI, MPRAGE, MP2RAGE, 3D SPACE T2, T2, and PD images to establish scanning parameters targeted at optimizing spatial resolution. Direct comparisons between 3 and 7 T were performed in two additional subjects using the finalized sequences (3 T: T2, PD, MPRAGE, SWAN; 7 T: 3D T2, MPRAGE, SWI, MP2RAGE). Artifacts and the depiction of structures were evaluated by two neuroradiologists using a standardized score sheet. Sequences could be established for high-resolution 7 T imaging even in caudal cranial areas. High in-plane resolution T2, PD, and SWI images provided depiction of inner brain stem structures such as pons fibers, raphe, reticular formation, nerve roots, and periaqueductal gray. MPRAGE and MP2RAGE provided clear depiction of the CNs. 3D T2 images improved depiction of inner brain structure in comparison to T2 images at 3 T. Although the 7-T SWI sequence provided improved contrast to some inner structures, extended areas were influenced by artifacts due to image disturbances from susceptibility differences. Seven-tesla imaging of basal brain areas is feasible and might have significant impact on detection and diagnosis in patients with specific diseases, e.g., trigeminal pain related to affection of the nerve root. Some inner brain stem structures can be depicted at 3 T, but certain sequences at 7 T, in particular 3D SPACE T2, are superior in producing anatomical in vivo images of deep brain stem structures. (orig.)

  20. Milrinone in Enterovirus 71 Brain Stem Encephalitis

    Directory of Open Access Journals (Sweden)

    SHIH-MIN eWANG

    2016-03-01

    Full Text Available Enterovirus 71 (EV71 was implicated in a widespread outbreak of hand-foot-and-mouth disease (HFMD across the Asia Pacific area since 1997 and has also been reported sporadically in patients with brain stem encephalitis. Neurogenic shock with pulmonary edema (PE is a fatal complication of EV71 infection. Among inotropic agents, milrinone is selected as a therapeutic agent for EV71- induced PE due to its immunopathogenesis. Milrinone is a type III phosphodiesterase inhibitor that has both inotropic and vasodilator effects. Its clinical efficacy has been shown by modulating inflammation, reducing sympathetic over-activity, and improving survival in patients with EV71-associated PE. Milrinone exhibits immunoregulatory and anti-inflammatory effects in the management of systemic inflammatory responses in severe EV71 infection.

  1. Optimized Longitudinal Monitoring of Stem Cell Grafts in Mouse Brain Using a Novel Bioluminescent/Near Infrared Fluorescent Fusion Reporter

    NARCIS (Netherlands)

    L. Mezzanotte (Laura); Iljas, J.D. (Juvita Delancy); I. Que (Ivo); A. Chan (Albert); E.L. Kaijzel (Eric); R.C. Hoeben (Rob); C.W.G.M. Löwik (Clemens)

    2017-01-01

    textabstractBiodistribution and fate of transplanted stem cells via longitudinal monitoring has been successfully achieved in the last decade using optical imaging. However, sensitive longitudinal imaging of transplanted stem cells in deep tissue like the brain remains challenging not only due to

  2. [Dislocated fracture of the lesser trochanter with malrotation of the stem after robot assisted implantation of a cementless hip prosthesis: a casuistic report].

    Science.gov (United States)

    Prymka, M; Hassenpflug, J

    2003-08-01

    This paper presents the case of a 63 year old female with a severe coxarthrosis. She got a robot assited implantation of a cementless hip prosthesis (Osteolock, Stryker-Howmedica, Mühlheim). As operation robot the CASPAR-System (Orto-Maquet, Rastatt) was used. Initially, the clinical progress of the patient was fine. She was nearly painfree within 14 days and showed an acceptable range of motion in the operated joint (flexion/ extension 90 degrees /05 degrees /00 degrees ). She was mobilized with crutches and 15 kg weight bearing at the operated leg. 3 weeks postoperative the patient complaint about increasing pain without trauma or intensification of the weight bearing. X-rays showed not only a dislocated fracture of the lesser trochanter, but also a sinking combined with a malrotation of the stem. A revision operation was necessary,where we implanted a cemented stem. Now clinical progress was completely satisfying.

  3. The surgical viability and radiological monitoring of brain implants of bioactive micro-seeds in an animal model

    International Nuclear Information System (INIS)

    Silva, Giane X.O.; Campos, Tarcisio Passos Ribeiro de; Siqueira, Savio Lana; Maciel, Marcelo B.

    2005-01-01

    The interstitial implant is a therapeutic modality in brachytherapy of the head and neck. Presently, the seeds implanted in tumors in the central nervous system are metallic I-125. After the full emission of the radionuclide, the seed remains inert in the implanted area. Bioactive ceramic seeds have been prepared for this research group incorporating Sm-152 to be active in Sm-153. The main goal of the present study is the development of a the surgical technique for implanting the biodegradable radioactive micro-seeds in the brains of rabbits, as well as the observation of the clinical reactions of the animal after implantation of two sets of three seeds. The surgical procedure consisted of performing two separate perforations 10 mm from each other in the skull, permitting the implantation of two groups of three seeds, totaling six seeds. The results of the pilot study showed the effectiveness of the surgical procedure and of the biocompatibility of the seeds and the lack of presence of adverse reactions, functional sequels, or inflammation in a follow up 50 days post-surgery. Such seeds of reduced volume, 0.2 x 1.6 mm, could be monitored by computerized tomography 30 days after implanting. (author)

  4. A wirelessly controlled implantable LED system for deep brain optogenetic stimulation

    Science.gov (United States)

    Rossi, Mark A.; Go, Vinson; Murphy, Tracy; Fu, Quanhai; Morizio, James; Yin, Henry H.

    2015-01-01

    In recent years optogenetics has rapidly become an essential technique in neuroscience. Its temporal and spatial specificity, combined with efficacy in manipulating neuronal activity, are especially useful in studying the behavior of awake behaving animals. Conventional optogenetics, however, requires the use of lasers and optic fibers, which can place considerable restrictions on behavior. Here we combined a wirelessly controlled interface and small implantable light-emitting diode (LED) that allows flexible and precise placement of light source to illuminate any brain area. We tested this wireless LED system in vivo, in transgenic mice expressing channelrhodopsin-2 in striatonigral neurons expressing D1-like dopamine receptors. In all mice tested, we were able to elicit movements reliably. The frequency of twitches induced by high power stimulation is proportional to the frequency of stimulation. At lower power, contraversive turning was observed. Moreover, the implanted LED remains effective over 50 days after surgery, demonstrating the long-term stability of the light source. Our results show that the wireless LED system can be used to manipulate neural activity chronically in behaving mice without impeding natural movements. PMID:25713516

  5. Progressive multifocal leukoencephalopathy limited to the brain stem

    Energy Technology Data Exchange (ETDEWEB)

    Kastrup, O.; Maschke, M.; Diener, H.C. [Neurologische Universitaetsklinik, University of Essen (Germany); Wanke, I. [Department of Neuroradiology, University of Essen (Germany)

    2002-03-01

    Progressive multifocal leukoencephalopathy (PML) is a subacute demyelinating slow-virus encephalitis caused by the JC polyomavirus in 2-5% of patients with AIDS. MRI typically shows multiple lesions in the cerebral hemispheres. We present a rare case of rapidly evolving and lethal PML with a severe bulbar syndrome and spastic tetraparesis in a patient with AIDS. MRI showed high-signal lesions on T2-weighted images confined to the brain stem, extending from the medulla oblongata to the midbrain. JC virus polymerase chain reaction in cerebrospinal fluid was positive, and neuropathology showed the findings of PML. This case was also notable because of the rapid progression despite improved immune status with antiretroviral therapy. (orig.)

  6. Brain Injury Expands the Numbers of Neural Stem Cells and Progenitors in the SVZ by Enhancing Their Responsiveness to EGF

    Directory of Open Access Journals (Sweden)

    Dhivyaa Alagappan

    2009-04-01

    Full Text Available There is an increase in the numbers of neural precursors in the SVZ (subventricular zone after moderate ischaemic injuries, but the extent of stem cell expansion and the resultant cell regeneration is modest. Therefore our studies have focused on understanding the signals that regulate these processes towards achieving a more robust amplification of the stem/progenitor cell pool. The goal of the present study was to evaluate the role of the EGFR [EGF (epidermal growth factor receptor] in the regenerative response of the neonatal SVZ to hypoxic/ischaemic injury. We show that injury recruits quiescent cells in the SVZ to proliferate, that they divide more rapidly and that there is increased EGFR expression on both putative stem cells and progenitors. With the amplification of the precursors in the SVZ after injury there is enhanced sensitivity to EGF, but not to FGF (fibroblast growth factor-2. EGF-dependent SVZ precursor expansion, as measured using the neurosphere assay, is lost when the EGFR is pharmacologically inhibited, and forced expression of a constitutively active EGFR is sufficient to recapitulate the exaggerated proliferation of the neural stem/progenitors that is induced by hypoxic/ischaemic brain injury. Cumulatively, our results reveal that increased EGFR signalling precedes that increase in the abundance of the putative neural stem cells and our studies implicate the EGFR as a key regulator of the expansion of SVZ precursors in response to brain injury. Thus modulating EGFR signalling represents a potential target for therapies to enhance brain repair from endogenous neural precursors following hypoxic/ischaemic and other brain injuries.

  7. Long-term meditation is associated with increased gray matter density in the brain stem

    DEFF Research Database (Denmark)

    Vestergaard-Poulsen, Peter; Beek, Martijn van; Skewes, Joshua

    2009-01-01

    density in lower brain stem regions of experienced meditators compared with age-matched nonmeditators. Our findings show that long-term practitioners of meditation have structural differences in brainstem regions concerned with cardiorespiratory control. This could account for some......Extensive practice involving sustained attention can lead to changes in brain structure. Here, we report evidence of structural differences in the lower brainstem of participants engaged in the long-term practice of meditation. Using magnetic resonance imaging, we observed higher gray matter...

  8. Realistic modeling of deep brain stimulation implants for electromagnetic MRI safety studies.

    Science.gov (United States)

    Guerin, Bastien; Serano, Peter; Iacono, Maria Ida; Herrington, Todd M; Widge, Alik S; Dougherty, Darin D; Bonmassar, Giorgio; Angelone, Leonardo M; Wald, Lawrence L

    2018-05-04

    We propose a framework for electromagnetic (EM) simulation of deep brain stimulation (DBS) patients in radiofrequency (RF) coils. We generated a model of a DBS patient using post-operative head and neck computed tomography (CT) images stitched together into a 'virtual CT' image covering the entire length of the implant. The body was modeled as homogeneous. The implant path extracted from the CT data contained self-intersections, which we corrected automatically using an optimization procedure. Using the CT-derived DBS path, we built a model of the implant including electrodes, helicoidal internal conductor wires, loops, extension cables, and the implanted pulse generator. We also built four simplified models with straight wires, no extension cables and no loops to assess the impact of these simplifications on safety predictions. We simulated EM fields induced by the RF birdcage body coil in the body model, including at the DBS lead tip at both 1.5 Tesla (64 MHz) and 3 Tesla (123 MHz). We also assessed the robustness of our simulation results by systematically varying the EM properties of the body model and the position and length of the DBS implant (sensitivity analysis). The topology correction algorithm corrected all self-intersection and curvature violations of the initial path while introducing minimal deformations (open-source code available at http://ptx.martinos.org/index.php/Main_Page). The unaveraged lead-tip peak SAR predicted by the five DBS models (0.1 mm resolution grid) ranged from 12.8 kW kg -1 (full model, helicoidal conductors) to 43.6 kW kg -1 (no loops, straight conductors) at 1.5 T (3.4-fold variation) and 18.6 kW kg -1 (full model, straight conductors) to 73.8 kW kg -1 (no loops, straight conductors) at 3 T (4.0-fold variation). At 1.5 T and 3 T, the variability of lead-tip peak SAR with respect to the conductivity ranged between 18% and 30%. Variability with respect to the position and length of the DBS implant ranged between 9.5% and 27.6%.

  9. An implantable integrated low-power amplifier-microelectrode array for Brain-Machine Interfaces.

    Science.gov (United States)

    Patrick, Erin; Sankar, Viswanath; Rowe, William; Sanchez, Justin C; Nishida, Toshikazu

    2010-01-01

    One of the important challenges in designing Brain-Machine Interfaces (BMI) is to build implantable systems that have the ability to reliably process the activity of large ensembles of cortical neurons. In this paper, we report the design, fabrication, and testing of a polyimide-based microelectrode array integrated with a low-power amplifier as part of the Florida Wireless Integrated Recording Electrode (FWIRE) project at the University of Florida developing a fully implantable neural recording system for BMI applications. The electrode array was fabricated using planar micromachining MEMS processes and hybrid packaged with the amplifier die using a flip-chip bonding technique. The system was tested both on bench and in-vivo. Acute and chronic neural recordings were obtained from a rodent for a period of 42 days. The electrode-amplifier performance was analyzed over the chronic recording period with the observation of a noise floor of 4.5 microVrms, and an average signal-to-noise ratio of 3.8.

  10. Initial Attempts of Development and Characterization of an In Vitro Blood Brain Barrier Model Derived from Human Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Goldeman, Charlotte; Saaby, Lasse; Hall, Vanessa Jane

    The human blood brain barrier has yet to be successfully replicated as an in vitro model. One of the more promising approaches has been to develop an in vitro model derived from human pluripotent stem cells. However, as promising as this model may be, a successful replication of the differentiation...... method on different kinds of pluripotent stem cell lines have yet to be accomplished. We try to approach the promising method as described by Stebbins et al. (2015) to differentiate human pluripotent stem cells into brain like endothelial cells (BECs). Five different human pluripotent stem cell lines...... configurations (mono culture, non-contact co-culture and contact co-culture) with primary rat astrocytes to induce barrier-like properties. Endothelial cell media supplemented with retinoic acid were then applied to the cells to ensure selective expansion of BECs. The different culture configurations were...

  11. Exogenous stem cells pioneer a biobridge to the advantage of host brain cells following stroke: New insights for clinical applications

    Directory of Open Access Journals (Sweden)

    Marci G Crowley

    2017-01-01

    Full Text Available Stroke continues to maintain its status as one of the top causes of mortality within the United States. Currently, the only Food and Drug Administration (FDA-approved drug in place for stroke patients, tissue plasminogen activator (tPA, has a rigid therapeutic window, closing at approximately 4.5 h after stroke onset. Due to this short time frame and other restrictions, such as any condition that increases a patient's risk for hemorrhaging, it has been predicted that <5% of ischemic stroke patients benefit from tPA. Given that rehabilitation therapy remains the only other option for stroke victims, there is a clear unmet clinical need for treatment available for the remaining 95%. While still considered an experimental treatment, the utilization of stem cell therapies for stroke holds consistent promise. Copious preclinical studies report the capacity for transplanted stem cells to rescue the brain parenchyma surrounding the stroke-induced infarct core. At present, the exact mechanisms in which stem cells contribute a robust therapeutic benefit remains unclear. Following stem cell administration, researchers have observed cell replacement, an increase in growth factors, and a reduction in inflammation. With a deeper understanding of the precise mechanism of stem cells, these therapies can be optimized in the clinic to afford the greatest therapeutic benefit. Recent studies have depicted a unique method of endogenous stem cell activation as a result of stem cell therapy. In both traumatic brain injury and stroke models, transplanted mesenchymal stromal cells (MSCs facilitated a pathway between the neurogenic niches of the brain and the damaged area through extracellular matrix remodeling. The biobridge pioneered by the MSCs was utilized by the endogenous stem cells, and these cells were able to travel to the damaged areas distal to the neurogenic niches, a feat unachievable without prior remodeling. These studies broaden our understanding of stem

  12. Brain implants for substituting lost motor function: state of the art and potential impact on the lives of motor-impaired seniors.

    Science.gov (United States)

    Ramsey, N F; Aarnoutse, E J; Vansteensel, M J

    2014-01-01

    Recent scientific achievements bring the concept of neural prosthetics for reinstating lost motor function closer to medical application. Current research involves severely paralyzed people under the age of 65, but implications for seniors with stroke or trauma-induced impairments are clearly on the horizon. Demographic changes will lead to a shortage of personnel to care for an increasing population of senior citizens, threatening maintenance of an acceptable level of care and urging ways for people to live longer at their home independent from personal assistance. This is particularly challenging when people suffer from disabilities such as partial paralysis after stroke or trauma, where daily personal assistance is required. For some of these people, neural prosthetics can reinstate some lost motor function and/or lost communication, thereby increasing independence and possibly quality of life. In this viewpoint article, we present the state of the art in decoding brain activity in the service of brain-computer interfacing. Although some noninvasive applications produce good results, we focus on brain implants that benefit from better quality brain signals. Fully implantable neural prostheses for home use are not available yet, but clinical trials are being prepared. More sophisticated systems are expected to follow in the years to come, with capabilities of interest for less severe paralysis. Eventually the combination of smart robotics and brain implants is expected to enable people to interact well enough with their environment to live an independent life in spite of motor disabilities. © 2014 S. Karger AG, Basel.

  13. Syringe needle skull penetration reduces brain injuries and secondary inflammation following intracerebral neural stem cell transplantation.

    Science.gov (United States)

    Gao, Mou; Dong, Qin; Zhang, Hongtian; Yang, Yang; Zhu, Jianwei; Yang, Zhijun; Xu, Minhui; Xu, Ruxiang

    2017-03-01

    Intracerebral neural stem cell (NSC) transplantation is beneficial for delivering stem cell grafts effectively, however, this approach may subsequently result in brain injury and secondary inflammation. To reduce the risk of promoting brain injury and secondary inflammation, two methods were compared in the present study. Murine skulls were penetrated using a drill on the left side and a syringe needle on the right. Mice were randomly divided into three groups (n=84/group): Group A, receiving NSCs in the left hemisphere and PBS in the right; group B, receiving NSCs in the right hemisphere and PBS in the left; and group C, receiving equal NSCs in both hemispheres. Murine brains were stained for morphological analysis and subsequent evaluation of infiltrated immune cells. ELISA was performed to detect neurotrophic and immunomodulatory factors in the brain. The findings indicated that brain injury and secondary inflammation in the left hemisphere were more severe than those in the right hemisphere, following NSC transplantation. In contrast to the left hemisphere, more neurotrophic factors but less pro-inflammatory cytokines were detected in the right hemisphere. In addition, increased levels of neurotrophic factors and interleukin (IL)-10 were observed in the NSC transplantation side when compared with the PBS-treated hemispheres, although lower levels of IL-6 and tumor necrosis factor-α were detected. In conclusion, the present study indicated that syringe needle skull penetration vs. drill penetration is an improved method that reduces the risk of brain injury and secondary inflammation following intracerebral NSC transplantation. Furthermore, NSCs have the potential to modulate inflammation secondary to brain injuries.

  14. Stem cell therapy to protect and repair the developing brain: a review of mechanisms of action of cord blood and amnion epithelial derived cells

    Directory of Open Access Journals (Sweden)

    Margie eCastillo-Melendez

    2013-10-01

    Full Text Available In the research, clinical and wider community there is great interest in the use of stem cells to reduce the progression, or indeed repair brain injury. Perinatal brain injury may result from acute or chronic insults sustained during fetal development, during the process of birth, or in the newborn period. The most readily identifiable outcome of perinatal brain injury is cerebral palsy, however this is just one consequence in a spectrum of mild to severe neurological deficits. As we review, there are now clinical trials taking place worldwide targeting cerebral palsy with stem cell therapies. It will likely be many years before strong evidence-based results emerge from these trials. With such trials underway, it is both appropriate and timely to address the physiological basis for the efficacy of stem-like cells in preventing damage to, or regenerating, the newborn brain. Appropriate experimental animal models are best placed to deliver this information. Cell availability, the potential for immunological rejection, ethical and logistical considerations, together with the propensity for native cells to form terratomas, make it unlikely that embryonic or fetal stem cells will be practical. Fortunately, these issues do not pertain to the use of human amnion epithelial cells (hAECs, or umbilical cord blood (UCB stem cells that are readily and economically obtained from the placenta and umbilical cord discarded at birth. These cells have the potential for transplantation to the newborn where brain injury is diagnosed or even suspected. We will explore the novel characteristics of hAECs and undifferentiated UCB cells, as well as UCB-derived endothelial progenitor cells and mesenchymal stem cells, and how immunomodulation and anti-inflammatory properties are principal mechanisms of action that are common to these cells, and which in turn may ameliorate the cerebral hypoxia and inflammation that are final pathways in the pathogenesis of perinatal brain

  15. Measurements of RF Heating during 3.0T MRI of a Pig Implanted with Deep Brain Stimulator

    Science.gov (United States)

    Gorny, Krzysztof R; Presti, Michael F; Goerss, Stephan J; Hwang, Sun C; Jang, Dong-Pyo; Kim, Inyong; Shu, Yunhong; Favazza, Christopher P; Lee, Kendall H; Bernstein, Matt A

    2012-01-01

    Purpose To present preliminary, in vivo temperature measurements during MRI of a pig implanted with a deep brain stimulation (DBS) system. Materials and Methods DBS system (Medtronic Inc., Minneapolis, MN) was implanted in the brain of an anesthetized pig. 3.0T MRI was performed with a T/R head coil using the low-SAR GRE EPI and IR-prepped GRE sequences (SAR: 0.42 W/kg and 0.39 W/kg, respectively), and the high-SAR 4-echo RF spin echo (SAR: 2.9 W/kg). Fluoroptic thermometry was used to directly measure RF-related heating at the DBS electrodes, and at the implantable pulse generator (IPG). For reference the measurements were repeated in the same pig at 1.5T and, at both field strengths, in a phantom. Results At 3.0T, the maximal temperature elevations at DBS electrodes were 0.46 °C and 2.3 °C, for the low- and high-SAR sequences, respectively. No heating was observed on the implanted IPG during any of the measurements. Measurements of in-vivo heating differed from those obtained in the phantom. Conclusion The 3.0T MRI using GRE EPI and IR-prepped GRE sequences resulted in local temperature elevations at DBS electrodes of no more than 0.46°C. Although no extrapolation should be made to human exams and much further study will be needed, these preliminary data are encouraging for the future use 3.0T MRI in patients with DBS. PMID:23228310

  16. Measurements of RF heating during 3.0-T MRI of a pig implanted with deep brain stimulator.

    Science.gov (United States)

    Gorny, Krzysztof R; Presti, Michael F; Goerss, Stephan J; Hwang, Sun C; Jang, Dong-Pyo; Kim, Inyong; Min, Hoon-Ki; Shu, Yunhong; Favazza, Christopher P; Lee, Kendall H; Bernstein, Matt A

    2013-06-01

    To present preliminary, in vivo temperature measurements during MRI of a pig implanted with a deep brain stimulation (DBS) system. DBS system (Medtronic Inc., Minneapolis, MN) was implanted in the brain of an anesthetized pig. 3.0-T MRI was performed with a T/R head coil using the low-SAR GRE EPI and IR-prepped GRE sequences (SAR: 0.42 and 0.39 W/kg, respectively), and the high-SAR 4-echo RF spin echo (SAR: 2.9 W/kg). Fluoroptic thermometry was used to directly measure RF-related heating at the DBS electrodes, and at the implantable pulse generator (IPG). For reference the measurements were repeated in the same pig at 1.5 T and, at both field strengths, in a phantom. At 3.0T, the maximal temperature elevations at DBS electrodes were 0.46 °C and 2.3 °C, for the low- and high-SAR sequences, respectively. No heating was observed on the implanted IPG during any of the measurements. Measurements of in vivo heating differed from those obtained in the phantom. The 3.0-T MRI using GRE EPI and IR-prepped GRE sequences resulted in local temperature elevations at DBS electrodes of no more than 0.46 °C. Although no extrapolation should be made to human exams and much further study will be needed, these preliminary data are encouraging for the future use 3.0-T MRI in patients with DBS. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Implanting Glioblastoma Spheroids into Rat Brains and Monitoring Tumor Growth by MRI Volumetry.

    Science.gov (United States)

    Löhr, Mario; Linsenmann, Thomas; Jawork, Anna; Kessler, Almuth F; Timmermann, Nils; Homola, György A; Ernestus, Ralf-Ingo; Hagemann, Carsten

    2017-01-01

    The outcome of patients suffering from glioblastoma multiforme (GBM) remains poor with a median survival of less than 15 months. To establish innovative therapeutical approaches or to analyze the effect of protein overexpression or protein knockdown by RNA interference in vivo, animal models are mandatory. Here, we describe the implantation of C6 glioma spheroids into the rats' brain and how to follow tumor growth by MRI scans. We show that C6 cells grown in Sprague-Dawley rats share several morphologic features of human glioblastoma like pleomorphic cells, areas of necrosis, vascular proliferation, and tumor cell invasion into the surrounding brain tissue. In addition, we describe a method for tumor volumetry utilizing the CISS 3D- or contrast-enhanced T1-weighted 3D sequence and freely available post-processing software.

  18. Early changes of auditory brain stem evoked response after radiotherapy for nasopharyngeal carcinoma - a prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Lau, S K; Wei, W I; Sham, J S.T.; Choy, D T.K.; Hui, Y [Queen Mary Hospital, Hong Kong (Hong Kong)

    1992-10-01

    A prospective study of the effect of radiotherapy for nasopharyngeal carcinoma on hearing was carried out on 49 patients who had pure tone, impedance audiometry and auditory brain stem evoked response (ABR) recordings before, immediately, three, six and 12 months after radiotherapy. Fourteen patients complained of intermittent tinnitus after radiotherapy. We found that 11 initially normal ears of nine patients developed a middle ear effusion, three to six months after radiotherapy. There was mixed sensorineural and conductive hearing impairment after radiotherapy. Persistent impairment of ABR was detected immediately after completion of radiotherapy. The waves I-III and I-V interpeak latency intervals were significantly prolonged one year after radiotherapy. The study shows that radiotherapy for nasopharyngeal carcinoma impairs hearing by acting on the middle ear, the cochlea and the brain stem auditory pathway. (Author).

  19. Early changes of auditory brain stem evoked response after radiotherapy for nasopharyngeal carcinoma - a prospective study

    International Nuclear Information System (INIS)

    Lau, S.K.; Wei, W.I.; Sham, J.S.T.; Choy, D.T.K.; Hui, Y.

    1992-01-01

    A prospective study of the effect of radiotherapy for nasopharyngeal carcinoma on hearing was carried out on 49 patients who had pure tone, impedance audiometry and auditory brain stem evoked response (ABR) recordings before, immediately, three, six and 12 months after radiotherapy. Fourteen patients complained of intermittent tinnitus after radiotherapy. We found that 11 initially normal ears of nine patients developed a middle ear effusion, three to six months after radiotherapy. There was mixed sensorineural and conductive hearing impairment after radiotherapy. Persistent impairment of ABR was detected immediately after completion of radiotherapy. The waves I-III and I-V interpeak latency intervals were significantly prolonged one year after radiotherapy. The study shows that radiotherapy for nasopharyngeal carcinoma impairs hearing by acting on the middle ear, the cochlea and the brain stem auditory pathway. (Author)

  20. Direct implantation versus platelet-rich fibrin-embedded adipose-derived mesenchymal stem cells in treating rat acute myocardial infarction.

    Science.gov (United States)

    Sun, Cheuk-Kwan; Zhen, Yen-Yi; Leu, Steve; Tsai, Tzu-Hsien; Chang, Li-Teh; Sheu, Jiunn-Jye; Chen, Yung-Lung; Chua, Sarah; Chai, Han-Tan; Lu, Hung-I; Chang, Hsueh-Wen; Lee, Fan-Yen; Yip, Hon-Kan

    2014-05-15

    This study tested whether adipose-derived mesenchymal stem cells (ADMSC) embedded in platelet-rich fibrin (PRF) scaffold is superior to direct ADMSC implantation in improving left ventricular (LV) performance and reducing LV remodeling in a rat acute myocardial infarction (AMI) model of left anterior descending coronary artery (LAD) ligation. Twenty-eight male adult Sprague Dawley rats equally divided into group 1 [sham control], group 2 (AMI only), group 3 (AMI+direct ADMSC implantation), and group 4 (AMI+PRF-embedded autologous ADMSC) were sacrificed on day 42 after AMI. LV systolic and diastolic dimensions and volumes, and infarct/fibrotic areas were highest in group 2, lowest in group 1 and significantly higher in group 3 than in group 4, whereas LV performance and LV fractional shortening exhibited a reversed pattern (p<0.005). Protein expressions of inflammation (oxidative stress, IL-1β, MMP-9), apoptosis (mitochondrial Bax, cleaved PARP), fibrosis (Smad3, TGF-β), and pressure-overload biomarkers (BNP, MHC-β) displayed a pattern similar to that of LV dimensions, whereas anti-inflammatory (IL-10), anti-apoptotic (Bcl-2), and anti-fibrotic (Smad1/5, BMP-2) indices showed a pattern similar to that of LV performance among the four groups (all p<0.05). Angiogenesis biomarkers at protein (CXCR4, SDF-1α, VEGF), cellular (CD31+, CXCR4+, SDF-1α+), and immunohistochemical (small vessels) levels, and cardiac stem cell markers (C-kit+, Sca-1+) in infarct myocardium were highest in group 4, lowest in group 1, and significantly higher in group 3 than in group 2 (all p<0.005). PRF-embedded ADMSC is superior to direct ADMSC implantation in preserving LV function and attenuating LV remodeling. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Effects of a hybrid micro/nanorod topography-modified titanium implant on adhesion and osteogenic differentiation in rat bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Zhang, Wenjie; Li, Zihui; Huang, Qingfeng; Xu, Ling; Li, Jinhua; Jin, Yuqin; Wang, Guifang; Liu, Xuanyong; Jiang, Xinquan

    2013-01-01

    Various methods have been used to modify titanium implant surfaces with the aim of achieving better osseointegration. In this study, we fabricated a clustered nanorod structure on an acid-etched, microstructured titanium plate surface using hydrogen peroxide. We also evaluated biofunctionalization of the hybrid micro/nanorod topography on rat bone marrow mesenchymal stem cells. Scanning electron microscopy and x-ray diffraction were used to investigate the surface topography and phase composition of the modified titanium plate. Rat bone marrow mesenchymal stem cells were cultured and seeded on the plate. The adhesion ability of the cells was then assayed by cell counting at one, 4, and 24 hours after cell seeding, and expression of adhesion-related protein integrin β1 was detected by immunofluorescence. In addition, a polymerase chain reaction assay, alkaline phosphatase and Alizarin Red S staining assays, and osteopontin and osteocalcin immunofluorescence analyses were used to evaluate the osteogenic differentiation behavior of the cells. The hybrid micro/nanoscale texture formed on the titanium surface enhanced the initial adhesion activity of the rat bone marrow mesenchymal stem cells. Importantly, the hierarchical structure promoted osteogenic differentiation of these cells. This study suggests that a hybrid micro/nanorod topography on a titanium surface fabricated by treatment with hydrogen peroxide followed by acid etching might facilitate osseointegration of a titanium implant in vivo.

  2. Dopaminergic differentiation of human neural stem cells mediated by co-cultured rat striatal brain slices

    DEFF Research Database (Denmark)

    Anwar, Mohammad Raffaqat; Andreasen, Christian Maaløv; Lippert, Solvej Kølvraa

    2008-01-01

    differentiation, we co-cultured cells from a human neural forebrain-derived stem cell line (hNS1) with rat striatal brain slices. In brief, coronal slices of neonatal rat striatum were cultured on semiporous membrane inserts placed in six-well trays overlying monolayers of hNS1 cells. After 12 days of co......Properly committed neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. To establish a setting for identification of secreted neural compounds promoting dopaminergic...

  3. Personalized hip implants manufacturing and testing

    Science.gov (United States)

    Croitoru, A. Sorin Mihai; Pacioga, B. Adrian; Comsa, C. Stanca

    2017-09-01

    Two models of Ti6Al4V personalized femoral stems for hip replacement have been designed and laser sintered with different sizes of fenestrated architecture that mimics the natural structure of bone, ensuring postoperative bone ingrowth and increasing the elasticity of the entire structure. They were tested statically and dynamically versus a commercial femoral stem. Mechanical tests were performed in order to determine the fatigue limit using the Locati method. The tests were conducted in a thermostatic bath (37°±1°) with the implants immersed in distilled water salted solution 0.91%. For probe embedment poly-methyl methacrylate (PMMA) was used. The characteristic curves of the two personalized fenestrated implants reveal an elastic behaviour by their nonlinear appearance. After dynamic tests an inverse relationship between displacements obtained in the static tests and the fatigue limit was observed. Large fenestrations conferred the desired elasticity to the implant, but contributed to a life service reduction. The fatigue limit for both implants was much above the minimum value specified by ISO 7602: 2010, so both models can be safely used in the medical practice, leading to increased life service of implants.

  4. Guidelines for the pathoanatomical examination of the lower brain stem in ingestive and swallowing disorders and its application to a dysphagic spinocerebellar ataxia type 3 patient

    NARCIS (Netherlands)

    Rub, U; Brunt, ER; Del Turco, D; de Vos, RAI; Gierga, K; Paulson, H; Braak, H

    Despite the fact that considerable progress has been made in the last 20 years regarding the three-phase process of ingestion and the lower brain stem nuclei involved in it, no comprehensive descriptions of the ingestion-related lower brain stem nuclei are available for neuropathologists confronted

  5. Realistic modeling of deep brain stimulation implants for electromagnetic MRI safety studies

    Science.gov (United States)

    Guerin, Bastien; Serano, Peter; Iacono, Maria Ida; Herrington, Todd M.; Widge, Alik S.; Dougherty, Darin D.; Bonmassar, Giorgio; Angelone, Leonardo M.; Wald, Lawrence L.

    2018-05-01

    We propose a framework for electromagnetic (EM) simulation of deep brain stimulation (DBS) patients in radiofrequency (RF) coils. We generated a model of a DBS patient using post-operative head and neck computed tomography (CT) images stitched together into a ‘virtual CT’ image covering the entire length of the implant. The body was modeled as homogeneous. The implant path extracted from the CT data contained self-intersections, which we corrected automatically using an optimization procedure. Using the CT-derived DBS path, we built a model of the implant including electrodes, helicoidal internal conductor wires, loops, extension cables, and the implanted pulse generator. We also built four simplified models with straight wires, no extension cables and no loops to assess the impact of these simplifications on safety predictions. We simulated EM fields induced by the RF birdcage body coil in the body model, including at the DBS lead tip at both 1.5 Tesla (64 MHz) and 3 Tesla (123 MHz). We also assessed the robustness of our simulation results by systematically varying the EM properties of the body model and the position and length of the DBS implant (sensitivity analysis). The topology correction algorithm corrected all self-intersection and curvature violations of the initial path while introducing minimal deformations (open-source code available at http://ptx.martinos.org/index.php/Main_Page). The unaveraged lead-tip peak SAR predicted by the five DBS models (0.1 mm resolution grid) ranged from 12.8 kW kg‑1 (full model, helicoidal conductors) to 43.6 kW kg‑1 (no loops, straight conductors) at 1.5 T (3.4-fold variation) and 18.6 kW kg‑1 (full model, straight conductors) to 73.8 kW kg‑1 (no loops, straight conductors) at 3 T (4.0-fold variation). At 1.5 T and 3 T, the variability of lead-tip peak SAR with respect to the conductivity ranged between 18% and 30%. Variability with respect to the position and length of the DBS implant ranged between 9

  6. In vitro delineation of human brain-stem anatomy using a small resonator: correlation with macroscopic and histological findings

    International Nuclear Information System (INIS)

    Maeurer, J.; Mitrovic, T.; Knollmann, F.D.; Luedtke, E.; Requardt

    1996-01-01

    Our purpose was to investigate the potential of an experimental animal coil using a commercial MRI unit to delineate the anatomical structure of the human brain stem. Three formaldehyde-fixed brain-stem specimens were examined by MRI and sectioned perpendicular to their longitudinal axis. The images were compared with gross anatomy and myelin-stained histological sections. Fibre tracts and nuclei which were not evident on examination of the unstained specimen were readily identified by MRI. Due to its inherent grey/white matter contrast, MRI with a high-resolution coil delineates anatomical structures in a way comparable to the myelin-stained histological sections. However, pigmented structures, readily visible on examination of the unstained specimen were discernible on neither MRI nor on myelin-stained sections. The excellent anatomical detail and grey/white matter contrast provided by these images could make MRI a useful adjunct to the pathologist investigating brain disease. (orig.)

  7. Effectiveness of mesenchymal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression

    OpenAIRE

    Lou Yongli; Guo Dewei; Zhang Hui; Song Laijun

    2016-01-01

    In this study, we investigated the therapeutic effects of Human Mesenchymal Stem Cells (hMSCs) cultured by hanging drop and conventional culturing methods on cerebellar repair in hypoxic-ischemic (HI) brain injured mice. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to analyze the expression levels of three stemness genes, Oct4, Sox2 and Nanog, and the migration related gene CXCR4. MSC prepared by hanging drop or conventional techniques were adminis...

  8. Composition and function of macroencapsulated human embryonic stem cell-derived implants: comparison with clinical human islet cell grafts.

    Science.gov (United States)

    Motté, Evi; Szepessy, Edit; Suenens, Krista; Stangé, Geert; Bomans, Myriam; Jacobs-Tulleneers-Thevissen, Daniel; Ling, Zhidong; Kroon, Evert; Pipeleers, Daniel

    2014-11-01

    β-Cells generated from large-scale sources can overcome current shortages in clinical islet cell grafts provided that they adequately respond to metabolic variations. Pancreatic (non)endocrine cells can develop from human embryonic stem (huES) cells following in vitro derivation to pancreatic endoderm (PE) that is subsequently implanted in immune-incompetent mice for further differentiation. Encapsulation of PE increases the proportion of endocrine cells in subcutaneous implants, with enrichment in β-cells when they are placed in TheraCyte-macrodevices and predominantly α-cells when they are alginate-microencapsulated. At posttransplant (PT) weeks 20-30, macroencapsulated huES implants presented higher glucose-responsive plasma C-peptide levels and a lower proinsulin-over-C-peptide ratio than human islet cell implants under the kidney capsule. Their ex vivo analysis showed the presence of single-hormone-positive α- and β-cells that exhibited rapid secretory responses to increasing and decreasing glucose concentrations, similar to isolated human islet cells. However, their insulin secretory amplitude was lower, which was attributed in part to a lower cellular hormone content; it was associated with a lower glucose-induced insulin biosynthesis, but not with lower glucagon-induced stimulation, which together is compatible with an immature functional state of the huES-derived β-cells at PT weeks 20-30. These data support the therapeutic potential of macroencapsulated huES implants but indicate the need for further functional analysis. Their comparison with clinical-grade human islet cell grafts sets references for future development and clinical translation. Copyright © 2014 the American Physiological Society.

  9. Preclinical trial of a novel surface architecture for improved primary fixation of cementless orthopaedic implants.

    Science.gov (United States)

    Harrison, Noel; Field, John R; Quondamatteo, Fabio; Curtin, William; McHugh, Peter E; Mc Donnell, Pat

    2014-09-01

    A new surface architecture for cementless orthopaedic implants (OsteoAnchor), which incorporates a multitude of tiny anchor features for enhancing primary fixation, was tested in an ovine hemi-arthroplasty pilot study. Test animals were implanted with a hip stem component incorporating the OsteoAnchor surface architecture produced using additive layer manufacturing and control animals were implanted with stems containing a standard plasma sprayed titanium coating. Intra-operative surgeon feedback indicated that superior primary fixation was achieved for the OsteoAnchor stems and rapid return to normal gait and load bearing was observed post-operation. Following a 16-week recovery time, histological evaluation of the excised femurs revealed in-growth of healthy bone into the porous structure of the OsteoAnchor stems. Bone in-growth was not achieved for the plasma sprayed stems. These results indicate the potential for the OsteoAnchor surface architecture to enhance both the initial stability and long term lifetime of cementless orthopaedic implants. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Distribution of calcium channel Ca(V)1.3 immunoreactivity in the rat spinal cord and brain stem.

    Science.gov (United States)

    Sukiasyan, N; Hultborn, H; Zhang, M

    2009-03-03

    The function of local networks in the CNS depends upon both the connectivity between neurons and their intrinsic properties. An intrinsic property of spinal motoneurons is the presence of persistent inward currents (PICs), which are mediated by non-inactivating calcium (mainly Ca(V)1.3) and/or sodium channels and serve to amplify neuronal input signals. It is of fundamental importance for the prediction of network function to determine the distribution of neurons possessing the ion channels that produce PICs. Although the distribution pattern of Ca(V)1.3 immunoreactivity (Ca(V)1.3-IR) has been studied in some specific central nervous regions in some species, so far no systematic investigations have been performed in both the rat spinal cord and brain stem. In the present study this issue was investigated by immunohistochemistry. The results indicated that the Ca(V)1.3-IR neurons were widely distributed across different parts of the spinal cord and the brain stem although with variable labeling intensities. In the spinal gray matter large neurons in the ventral horn (presumably motoneurons) tended to display higher levels of immunoreactivity than smaller neurons in the dorsal horn. In the white matter, a subset of glial cells labeled by an oligodendrocyte marker was also Ca(V)1.3-positive. In the brain stem, neurons in the motor nuclei appeared to have higher levels of immunoreactivity than those in the sensory nuclei. Moreover, a number of nuclei containing monoaminergic cells, for example the locus coeruleus, were also strongly immunoreactive. Ca(V)1.3-IR was consistently detected in the neuronal perikarya regardless of the neuronal type. However, in the large neurons in the spinal ventral horn and the cranial motor nuclei the Ca(V)1.3-IR was clearly detectable in first and second order dendrites. These results indicate that in the rat spinal cord and brain stem Ca(V)1.3 is probably a common calcium channel used by many kinds of neurons to facilitate the neuronal

  11. Bone marrow stem cells delivered into the subarachnoid space via cisterna magna improve repair of injured rat spinal cord white matter

    Science.gov (United States)

    Marcol, Wiesław; Slusarczyk, Wojciech; Sieroń, Aleksander L; Koryciak-Komarska, Halina; Lewin-Kowalik, Joanna

    2015-01-01

    The influence of bone marrow stem cells on regeneration of spinal cord in rats was investigated. Young adult male Wistar rats were used (n=22). Focal injury of spinal cord white matter at Th10 level was produced using our original non-laminectomy method by means of high-pressured air stream. Cells from tibial and femoral bone marrow of 1-month old rats (n=3) were cultured, labeled with BrdU/Hoechst and injected into cisterna magna (experimental group) three times: immediately after spinal cord injury and 3 as well as 7 days later. Neurons in brain stem and motor cortex were labeled with FluoroGold (FG) delivered caudally from the injury site a week before the end of experiment. Functional outcome and morphological features of regeneration were analyzed during 12-week follow-up. The lesions were characterized by means of MRI. Maximal distance of expansion of implanted cells in the spinal cord was measured and the number of FG-positive neurons in the brain was counted. Rats treated with stem cells presented significant improvement of locomotor performance and spinal cord morphology when compared to the control group. Distance covered by stem cells was 7 mm from the epicenter of the injury. Number of brain stem and motor cortex FG-positive neurons in experimental group was significantly higher than in control. Obtained data showed that bone marrow stem cells are able to induce the repair of injured spinal cord white matter. The route of cells application via cisterna magna appeared to be useful for their delivery in spinal cord injury therapy. PMID:26628950

  12. Neural stem cells improve neuronal survival in cultured postmortem brain tissue from aged and Alzheimer patients

    NARCIS (Netherlands)

    Wu, L.; Sluiter, A.A.; Guo, Ho Fu; Balesar, R. A.; Swaab, D. F.; Zhou, Jiang Ning; Verwer, R. W H

    Neurodegenerative diseases are progressive and incurable and are becoming ever more prevalent. To study whether neural stem cell can reactivate or rescue functions of impaired neurons in the human aging and neurodegenerating brain, we co-cultured postmortem slices from Alzheimer patients and control

  13. Hematopoietic differentiative properties of murine spleen implanted in the omenta of irradiated and nonirradiated hosts

    Energy Technology Data Exchange (ETDEWEB)

    Haley, J E; Tjio, J H; Smith, W W; Brecher, G [California Univ., San Francisco (USA); National Inst. of Arthritis, Metabolism, and Digestive Diseases, Bethesda, Md. (USA); National Cancer Inst., Bethesda, Md. (USA). Lab. of Viral Oncology)

    1975-01-01

    Whole body irradiation of the recipients of syngeneic splenic implants into the omentum greatly enhances hematopoiesis and permits survival of and repopulation by stem cells of donor origin. Donor hematopoietic stem cells do not survive in spleen implants of the nonirradiated host.Irradiated hosts were therefore used in the bulk of the experiments. Differentiation in the implants of splenic fragments is predominantly erythrocytic at 10 days and shifts to predominantly granulocytic differentiation at 21 days. Suspensions of spleen cells injected into the omentum are predominantly granulocytopoietic at 10 days. The differentiation in fragments of spleen depleted of stem cells by irradiation, seeded with bone marrow cells and implanted into the omentum results in mixed erythrocytic and granulocytic hematopoiesis, with granulocytic predominance. Lymphocytic cells appeared late in the implants of irradiated recipients even at a time of prolific lymphocytopoiesis in the hosts' own spleens. The cause of the delay in the implants is not clear. The data are consistent with the concept that differentiation of hematopoietic stem cells is influenced by the stromal cells of the parent organ. The erythrocytic inductive capacity of the stromal cells may belost by mechanical disruption or modified by irradiation or a prolonged period of implantation.

  14. Reelin signaling in the migration of ventral brain stem and spinal cord neurons

    Directory of Open Access Journals (Sweden)

    Sandra eBlaess

    2016-03-01

    Full Text Available The extracellular matrix protein Reelin is an important orchestrator of neuronal migration during the development of the central nervous system. While its role and mechanism of action have been extensively studied and reviewed in the formation of dorsal laminar brain structures like the cerebral cortex, hippocampus, and cerebellum, its functions during the neuronal migration events that result in the nuclear organization of the ventral central nervous system are less well understood. In an attempt to delineate an underlying pattern of Reelin action in the formation of neuronal cell clusters, this review highlights the role of Reelin signaling in the migration of neuronal populations that originate in the ventral brain stem and the spinal cord.

  15. Sex differences in morphology of the brain stem and cerebellum with normal ageing

    International Nuclear Information System (INIS)

    Oguro, H.; Okada, K.; Yamaguchi, S.; Kobayashi, S.

    1998-01-01

    The cerebral hemispheres become atrophic with age. The sex of the individual may affect this process. There are few studies of the effects of age and sex on the brain stem and cerebellum. We used MRI morphometry to study changes in these structures in 152 normal subjects over 40 years of age. In the linear measurements, men showed significant age-associated atrophy in the tegmentum and pretectum of the midbrain and the base of the pons. In women, only the pretectum of the midbrain showed significant ageing effects after the age of 50 years, and thereafter remained rather constant. Only men had significant age-associated reduction in area of the crebellar vermis area after the age of 70 years. Both men and women showed supratentorial brain atrophy that progressed by decades. There were significant correlations between supratentorial brain atrophy and the diameter of the ventral midbrain, pretectum, and base of the pons in men, and between brain atrophy and the diameter of the fourth ventricle in women. (orig.)

  16. Sex differences in morphology of the brain stem and cerebellum with normal ageing

    Energy Technology Data Exchange (ETDEWEB)

    Oguro, H.; Okada, K.; Yamaguchi, S.; Kobayashi, S. [Internal Medicine III, Shimane Medical University, Izumo (Japan)

    1998-12-01

    The cerebral hemispheres become atrophic with age. The sex of the individual may affect this process. There are few studies of the effects of age and sex on the brain stem and cerebellum. We used MRI morphometry to study changes in these structures in 152 normal subjects over 40 years of age. In the linear measurements, men showed significant age-associated atrophy in the tegmentum and pretectum of the midbrain and the base of the pons. In women, only the pretectum of the midbrain showed significant ageing effects after the age of 50 years, and thereafter remained rather constant. Only men had significant age-associated reduction in area of the crebellar vermis area after the age of 70 years. Both men and women showed supratentorial brain atrophy that progressed by decades. There were significant correlations between supratentorial brain atrophy and the diameter of the ventral midbrain, pretectum, and base of the pons in men, and between brain atrophy and the diameter of the fourth ventricle in women. (orig.) With 4 figs., 3 tabs., 16 refs.

  17. Tomographic criteria of gliomas in the brain stem in infants

    International Nuclear Information System (INIS)

    Machado Junior, M.A.; Bracchi, M.; D'Incerti, L.; Passerini, A.

    1994-01-01

    The relationship between Computed Tomography Imaging, histopathological and prognostic data is evaluated by reviewing 37 cases of brain stem neoplasm in infants. The results indicate a presence of a cystic lesion with solid mural nodule as the single prognostic criteria of a greater survival rate. Such finding frequently corresponds to Pilocytic Astrocytomas. No correlations between contrast enhancement and prognostic was found. The association between the prognostic value to the densitometric characteristics of the lesions was not possible. It was concluded that the evaluations of the extension of such lesion is fundamental. Therefore, Magnetic Resonance Imaging has more value than computed tomography. (M.A.C.)

  18. Murine cytomegalovirus infection of neural stem cells alters neurogenesis in the developing brain.

    Directory of Open Access Journals (Sweden)

    Manohar B Mutnal

    2011-01-01

    Full Text Available Congenital cytomegalovirus (CMV brain infection causes serious neuro-developmental sequelae including: mental retardation, cerebral palsy, and sensorineural hearing loss. But, the mechanisms of injury and pathogenesis to the fetal brain are not completely understood. The present study addresses potential pathogenic mechanisms by which this virus injures the CNS using a neonatal mouse model that mirrors congenital brain infection. This investigation focused on, analysis of cell types infected with mouse cytomegalovirus (MCMV and the pattern of injury to the developing brain.We used our MCMV infection model and a multi-color flow cytometry approach to quantify the effect of viral infection on the developing brain, identifying specific target cells and the consequent effect on neurogenesis. In this study, we show that neural stem cells (NSCs and neuronal precursor cells are the principal target cells for MCMV in the developing brain. In addition, viral infection was demonstrated to cause a loss of NSCs expressing CD133 and nestin. We also showed that infection of neonates leads to subsequent abnormal brain development as indicated by loss of CD24(hi cells that incorporated BrdU. This neonatal brain infection was also associated with altered expression of Oct4, a multipotency marker; as well as down regulation of the neurotrophins BDNF and NT3, which are essential to regulate the birth and differentiation of neurons during normal brain development. Finally, we report decreased expression of doublecortin, a marker to identify young neurons, following viral brain infection.MCMV brain infection of newborn mice causes significant loss of NSCs, decreased proliferation of neuronal precursor cells, and marked loss of young neurons.

  19. Brain Stem Infarction Due to Basilar Artery Dissection in a Patient with Moyamoya Disease Four Years after Successful Bilateral Revascularization Surgeries.

    Science.gov (United States)

    Abe, Takatsugu; Fujimura, Miki; Mugikura, Shunji; Endo, Hidenori; Tominaga, Teiji

    2016-06-01

    Moyamoya disease (MMD) is a rare cerebrovascular disease with an unknown etiology and is characterized by intrinsic fragility in the intracranial vascular walls such as the affected internal elastic lamina and thinning medial layer. The association of MMD with intracranial arterial dissection is extremely rare, whereas that with basilar artery dissection (BAD) has not been reported previously. A 46-year-old woman developed brain stem infarction due to BAD 4 years after successful bilateral superficial temporal artery-middle cerebral artery anastomosis with indirect pial synangiosis for ischemic-onset MMD. She presented with sudden occipitalgia and subsequently developed transient dysarthria and mild hemiparesis. Although a transient ischemic attack was initially suspected, her condition deteriorated in a manner that was consistent with left hemiplegia with severe dysarthria. Magnetic resonance (MR) imaging revealed brain stem infarction, and MR angiography delineated a double-lumen sign in the basilar artery, indicating BAD. She was treated conservatively and brain stem infarction did not expand. One year after the onset of brain stem infarction, her activity of daily living is still dependent (modified Rankin Scale of 4), and there were no morphological changes associated with BAD or recurrent cerebrovascular events during the follow-up period. The association of MMD with BAD is extremely rare. While considering the common underlying pathology such as an affected internal elastic lamina and fragile medial layer, the occurrence of BAD in a patient with MMD in a stable hemodynamic state is apparently unique. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  20. Neural stem cells in the immature, but not the mature, subventricular zone respond robustly to traumatic brain injury.

    Science.gov (United States)

    Goodus, Matthew T; Guzman, Alanna M; Calderon, Frances; Jiang, Yuhui; Levison, Steven W

    2015-01-01

    Pediatric traumatic brain injury is a significant problem that affects many children each year. Progress is being made in developing neuroprotective strategies to combat these injuries. However, investigators are a long way from therapies to fully preserve injured neurons and glia. To restore neurological function, regenerative strategies will be required. Given the importance of stem cells in repairing damaged tissues and the known persistence of neural precursors in the subventricular zone (SVZ), we evaluated regenerative responses of the SVZ to a focal brain lesion. As tissues repair more slowly with aging, injury responses of male Sprague Dawley rats at 6, 11, 17, and 60 days of age and C57Bl/6 mice at 14 days of age were compared. In the injured immature animals, cell proliferation in the dorsolateral SVZ more than doubled by 48 h. By contrast, the proliferative response was almost undetectable in the adult brain. Three approaches were used to assess the relative numbers of bona fide neural stem cells, as follows: the neurosphere assay (on rats injured at postnatal day 11, P11), flow cytometry using a novel 4-marker panel (on mice injured at P14) and staining for stem/progenitor cell markers in the niche (on rats injured at P17). Precursors from the injured immature SVZ formed almost twice as many spheres as precursors from uninjured age-matched brains. Furthermore, spheres formed from the injured brain were larger, indicating that the neural precursors that formed these spheres divided more rapidly. Flow cytometry revealed a 2-fold increase in the percentage of stem cells, a 4-fold increase in multipotential progenitor-3 cells and a 2.5-fold increase in glial-restricted progenitor-2/multipotential-3 cells. Analogously, there was a 2-fold increase in the mitotic index of nestin+/Mash1- immunoreactive cells within the immediately subependymal region. As the early postnatal SVZ is predominantly generating glial cells, an expansion of precursors might not

  1. Trans-differentiation of neural stem cells: a therapeutic mechanism against the radiation induced brain damage.

    Directory of Open Access Journals (Sweden)

    Kyeung Min Joo

    Full Text Available Radiation therapy is an indispensable therapeutic modality for various brain diseases. Though endogenous neural stem cells (NSCs would provide regenerative potential, many patients nevertheless suffer from radiation-induced brain damage. Accordingly, we tested beneficial effects of exogenous NSC supplementation using in vivo mouse models that received whole brain irradiation. Systemic supplementation of primarily cultured mouse fetal NSCs inhibited radiation-induced brain atrophy and thereby preserved brain functions such as short-term memory. Transplanted NSCs migrated to the irradiated brain and differentiated into neurons, astrocytes, or oligodendrocytes. In addition, neurotrophic factors such as NGF were significantly increased in the brain by NSCs, indicating that both paracrine and replacement effects could be the therapeutic mechanisms of NSCs. Interestingly, NSCs also differentiated into brain endothelial cells, which was accompanied by the restoration the cerebral blood flow that was reduced from the irradiation. Inhibition of the VEGF signaling reduced the migration and trans-differentiation of NSCs. Therefore, trans-differentiation of NSCs into brain endothelial cells by the VEGF signaling and the consequential restoration of the cerebral blood flow would also be one of the therapeutic mechanisms of NSCs. In summary, our data demonstrate that exogenous NSC supplementation could prevent radiation-induced functional loss of the brain. Therefore, successful combination of brain radiation therapy and NSC supplementation would provide a highly promising therapeutic option for patients with various brain diseases.

  2. Interactive, three dimensional, CT-based treatment planning of stereotaxic I-125 brain implants. 132

    International Nuclear Information System (INIS)

    Lulu, B.; Lewis, J.; Smith, V.; Stuart, A.

    1987-01-01

    Brain implants of I-125 seeds are done with the Brown-Roberts-Wells stereotaxic frame. The patient is CT scanned with the frame bolted to the skull. In the time between the scan and surgery, while the patient is under anesthesia, an interactive three dimensional CT-based treatment plan is performed on a VAX computer. The program is menu driven, easy to use, and easily modifiable. Device dependencies are limited to a small number of subroutines, and an array processor is used to speed dose calculations

  3. Human Neural Stem Cell Transplantation Rescues Functional Deficits in R6/2 and Q140 Huntington's Disease Mice

    Directory of Open Access Journals (Sweden)

    Jack C. Reidling

    2018-01-01

    Full Text Available Huntington's disease (HD is an inherited neurodegenerative disorder with no disease-modifying treatment. Expansion of the glutamine-encoding repeat in the Huntingtin (HTT gene causes broad effects that are a challenge for single treatment strategies. Strategies based on human stem cells offer a promising option. We evaluated efficacy of transplanting a good manufacturing practice (GMP-grade human embryonic stem cell-derived neural stem cell (hNSC line into striatum of HD modeled mice. In HD fragment model R6/2 mice, transplants improve motor deficits, rescue synaptic alterations, and are contacted by nerve terminals from mouse cells. Furthermore, implanted hNSCs are electrophysiologically active. hNSCs also improved motor and late-stage cognitive impairment in a second HD model, Q140 knockin mice. Disease-modifying activity is suggested by the reduction of aberrant accumulation of mutant HTT protein and expression of brain-derived neurotrophic factor (BDNF in both models. These findings hold promise for future development of stem cell-based therapies.

  4. Long-term meditation is associated with increased gray matter density in the brain stem

    DEFF Research Database (Denmark)

    Vestergaard-Poulsen, Peter; Beek, Martijn van; Skewes, Joshua

    2009-01-01

    Extensive practice involving sustained attention can lead to changes in brain structure. Here, we report evidence of structural differences in the lower brainstem of participants engaged in the long-term practice of meditation. Using magnetic resonance imaging, we observed higher gray matter...... density in lower brain stem regions of experienced meditators compared with age-matched nonmeditators. Our findings show that long-term practitioners of meditation have structural differences in brainstem regions concerned with cardiorespiratory control. This could account for some...... of the cardiorespiratory parasympathetic effects and traits, as well as the cognitive, emotional, and immunoreactive impact reported in several studies of different meditation practices....

  5. Mid-term migration analysis of a femoral short-stem prosthesis: a five-year EBRA-FCA-study.

    Science.gov (United States)

    Freitag, Tobias; Fuchs, Michael; Woelfle-Roos, Julia V; Reichel, Heiko; Bieger, Ralf

    2018-05-01

    The objective of this study was to evaluate the mid-term migration pattern of a femoral short stem. Implant migration of 73 femoral short-stems was assessed by Ein-Bild-Roentgen-Analysis Femoral-Component-Analysis (EBRA-FCA) 5 years after surgery. Migration pattern of the whole group was analysed and compared to the migration pattern of implants "at risk" with a subsidence of more than 1.5 mm 2 years postoperative. Mean axial subsidence was 1.1 mm (-5.0 mm to 1.5 mm) after 60 months. There was a statistical significant axial migration until 2 years postoperative with settling thereafter. 2 years after surgery 18 of 73 Implants were classified "at risk." Nevertheless, all stems showed secondary stabilisation in the following period with no implant failure neither in the group of implants with early stabilisation nor the group with extensive early onset migration. In summary, even in the group of stems with more pronounced early subsidence, delayed settling occurred in all cases. The determination of a threshold of critical early femoral short stem subsidence is necessary because of the differing migration pattern described in this study with delayed settling of the Fitmore stem 2 years postoperatively compared to early settling within the first postoperative year described for conventional stems.

  6. Friction wear and dissolution of orthopedic implant systems

    International Nuclear Information System (INIS)

    Ektessabi, A.M.; Shikine, S.; Hamdi, M.; Kitamura, N.; Rokkum, M.; Johansson, C.

    2000-01-01

    Bio-medical implants release metallic elements during the long periods of time while inserted in the human body. The chemical interactions between the tissues and surface of the implants, and the mechanical friction of implants cause the release of metals into the human tissues. In this study we investigated the distribution and the chemical-state of the metallic elements in the tissues around a failed implant system using PIXE (proton induced x-ray emission) and SR-XRF (synchrotron radiation x-ray fluorescence) spectroscopies. The specimens were from the causes of patients with diagnosed arthritis. The implant consisted of a stem and a metal backing made of Ti-6Al-4V, an implant head made of stainless steel, and a polyethylene (PE) cup. Both the stem and the metal backing had a plasma-sprayed HAp surface coating. Distribution and concentration of dissolved elements in tissues surrounding implants were examined and quantified using PIXE analysis. Similar specimen from the same case was further investigated using SR-XRF analysis. Chemical-states of the dissolved elements were also studied by XAFS (x-ray absorption fine structure) analysis. From results of these measurements, it is confirmed that the tissues surrounding implants contained metallic elements such as Fe, Cr, Ni, and Ti. These elements are originated from the implant. Furthermore, it was made clear that the chemical-state of Fe had changed as a consequence of dissolution of Fe in the organic tissues. (author)

  7. Implantation of Neuronal Stem Cells Enhances Object Recognition without Increasing Neurogenesis after Lateral Fluid Percussion Injury in Mice

    Directory of Open Access Journals (Sweden)

    Laura B. Ngwenya

    2018-01-01

    Full Text Available Cognitive deficits after traumatic brain injury (TBI are debilitating and contribute to the morbidity and loss of productivity of over 10 million people worldwide. Cell transplantation has been linked to enhanced cognitive function after experimental traumatic brain injury, yet the mechanism of recovery is poorly understood. Since the hippocampus is a critical structure for learning and memory, supports adult neurogenesis, and is particularly vulnerable after TBI, we hypothesized that stem cell transplantation after TBI enhances cognitive recovery by modulation of endogenous hippocampal neurogenesis. We performed lateral fluid percussion injury (LFPI in adult mice and transplanted embryonic stem cell-derived neural progenitor cells (NPC. Our data confirm an injury-induced cognitive deficit in novel object recognition, a hippocampal-dependent learning task, which is reversed one week after NPC transplantation. While LFPI alone promotes hippocampal neurogenesis, as revealed by doublecortin immunolabeling of immature neurons, subsequent NPC transplantation prevents increased neurogenesis and is not associated with morphological maturation of endogenous injury-induced immature neurons. Thus, NPC transplantation enhances cognitive recovery early after LFPI without a concomitant increase in neuron numbers or maturation.

  8. Morphological and histochemical changes in the brain stem in case of experimental hemispheric intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    S. I. Tertishniy

    2015-10-01

    Full Text Available Aim. Investigation of the extent of morphological changes and activity of biogenic amines (according to the intensity of luminescence in the neurons of the brain stem in intracerebral hemorrhage (ICH. Methods and results. ICH was designed on 29 white rats of Vistar line by the administration of autologous blood in the cerebral hemisphere. It was revealed that increased luminescence intensity by 18.4±5.5% was registered in monoaminergic neurons in 1–6 hours after experimental ICH. After 12 hours – 1 day development of dislocation syndrome leads to mosaic focal ischemic neuronal injuries with maximum reduction in the level of catecholamines by 29.5±5.0% compared with control cases. Three–6 days after ICH on a background of selective neuronal necrosis in substantial number of neurons in the nuclei of the brainstem the level of catecholamines is significantly reduced. Conclusion. Disclosed observations reflect significant functional pathology of neurons responsible for the regulation of cardiorespiratory function and may underlie disturbances of integrative activity in the brain stem in general.

  9. Embryonic Stem Cell-Derived Mesenchymal Stem Cells (MSCs) Have a Superior Neuroprotective Capacity Over Fetal MSCs in the Hypoxic-Ischemic Mouse Brain.

    Science.gov (United States)

    Hawkins, Kate E; Corcelli, Michelangelo; Dowding, Kate; Ranzoni, Anna M; Vlahova, Filipa; Hau, Kwan-Leong; Hunjan, Avina; Peebles, Donald; Gressens, Pierre; Hagberg, Henrik; de Coppi, Paolo; Hristova, Mariya; Guillot, Pascale V

    2018-05-01

    Human mesenchymal stem cells (MSCs) have huge potential for regenerative medicine. In particular, the use of pluripotent stem cell-derived mesenchymal stem cells (PSC-MSCs) overcomes the hurdle of replicative senescence associated with the in vitro expansion of primary cells and has increased therapeutic benefits in comparison to the use of various adult sources of MSCs in a wide range of animal disease models. On the other hand, fetal MSCs exhibit faster growth kinetics and possess longer telomeres and a wider differentiation potential than adult MSCs. Here, for the first time, we compare the therapeutic potential of PSC-MSCs (ES-MSCs from embryonic stem cells) to fetal MSCs (AF-MSCs from the amniotic fluid), demonstrating that ES-MSCs have a superior neuroprotective potential over AF-MSCs in the mouse brain following hypoxia-ischemia. Further, we demonstrate that nuclear factor (NF)-κB-stimulated interleukin (IL)-13 production contributes to an increased in vitro anti-inflammatory potential of ES-MSC-conditioned medium (CM) over AF-MSC-CM, thus suggesting a potential mechanism for this observation. Moreover, we show that induced pluripotent stem cell-derived MSCs (iMSCs) exhibit many similarities to ES-MSCs, including enhanced NF-κB signaling and IL-13 production in comparison to AF-MSCs. Future studies should assess whether iMSCs also exhibit similar neuroprotective potential to ES-MSCs, thus presenting a potential strategy to overcome the ethical issues associated with the use of embryonic stem cells and providing a potential source of cells for autologous use against neonatal hypoxic-ischemic encephalopathy in humans. Stem Cells Translational Medicine 2018;7:439-449. © 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  10. A technique for accurate planning of stereotactic brain implants prior to head ring fixation

    International Nuclear Information System (INIS)

    Ulin, Kenneth; Bornstein, Linda E.; Ling, Marilyn N.; Saris, Stephen; Wu, Julian K.; Curran, Bruce H.; Wazer, David E.

    1997-01-01

    Purpose: A two-step procedure is described for accurate planning of stereotactic brain implants prior to head-ring fixation. Methods and Materials: Approximately 2 weeks prior to implant a CT scan without the head ring is performed for treatment-planning purposes. An entry point and a reference point, both marked with barium and later tattooed, facilitate planning and permit correlation of the images with a later CT scan. A plan is generated using a conventional treatment-planning system to determine the number and activity of I-125 seeds required and the position of each catheter. I-125 seed anisotropy is taken into account by means of a modification to the treatment planning program. On the day of the implant a second CT scan is performed with the head ring affixed to the skull and with the same points marked as in the previous scan. The planned catheter coordinates are then mapped into the coordinate system of the second CT scan by means of a manual translational correction and a computer-calculated rotational correction derived from the reference point coordinates in the two scans. Results: The rotational correction algorithm was verified experimentally in a Rando phantom before it was used clinically. For analysis of the results with individual patients a third CT scan is performed 1 day following the implant and is used for calculating the final dosimetry. Conclusion: The technique that is described has two important advantages: 1) the number and activity of seeds required can be accurately determined in advance; and 2) sufficient time is allowed to derive the best possible plan

  11. Stab injury and device implantation within the brain results in inversely multiphasic neuroinflammatory and neurodegenerative responses

    Science.gov (United States)

    Potter, Kelsey A.; Buck, Amy C.; Self, Wade K.; Capadona, Jeffrey R.

    2012-08-01

    An estimated 25 million people in the US alone rely on implanted medical devices, ˜2.5 million implanted within the nervous system. Even though many devices perform adequately for years, the host response to medical devices often severely limits tissue integration and long-term performance. This host response is believed to be particularly limiting in the case of intracortical microelectrodes, where it has been shown that glial cell encapsulation and localized neuronal cell loss accompany intracortical microelectrode implantation. Since neuronal ensembles must be within ˜50 µm of the electrode to obtain neuronal spikes and local field potentials, developing a better understanding of the molecular and cellular environment at the device-tissue interface has been the subject of significant research. Unfortunately, immunohistochemical studies of scar maturation in correlation to device function have been inconclusive. Therefore, here we present a detailed quantitative study of the cellular events and the stability of the blood-brain barrier (BBB) following intracortical microelectrode implantation and cortical stab injury in a chronic survival model. We found two distinctly inverse multiphasic profiles for neuronal survival in device-implanted tissue compared to stab-injured animals. For chronically implanted animals, we observed a biphasic paradigm between blood-derived/trauma-induced and CNS-derived inflammatory markers driving neurodegeneration at the interface. In contrast, stab injured animals demonstrated a CNS-mediated neurodegenerative environment. Collectively these data provide valuable insight to the possibility of multiple roles of chronic neuroinflammatory events on BBB disruption and localized neurodegeneration, while also suggesting the importance to consider multiphasic neuroinflammatory kinetics in the design of therapeutic strategies for stabilizing neural interfaces.

  12. Gold ions bio-released from metallic gold particles reduce inflammation and apoptosis and increase the regenerative responses in focal brain injury

    DEFF Research Database (Denmark)

    Larsen, Agnete; Kolind, Kristian; Pedersen, Dan Sonne

    2008-01-01

    neural stem cell response. We conclude that bio-liberated gold ions possess pronounced anti-inflammatory and neuron-protective capacities in the brain and suggest that metallic gold has clinical potentials. Intra-cerebral application of metallic gold as a pharmaceutical source of gold ions represents......Traumatic brain injury results in loss of neurons caused as much by the resulting neuroinflammation as by the injury. Gold salts are known to be immunosuppressive, but their use are limited by nephrotoxicity. However, as we have proven that implants of pure metallic gold release gold ions which do...... not spread in the body, but are taken up by cells near the implant, we hypothesize that metallic gold could reduce local neuroinflammation in a safe way. Bio-liberation, or dissolucytosis, of gold ions from metallic gold surfaces requires the presence of disolycytes i.e. macrophages and the process...

  13. Human Umbilical Cord Blood Stem Cells: Rational for Use as a Neuroprotectant in Ischemic Brain Disease

    Directory of Open Access Journals (Sweden)

    Hadar Arien-Zakay

    2010-09-01

    Full Text Available The use of stem cells for reparative medicine was first proposed more than three decades ago. Hematopoietic stem cells from bone marrow, peripheral blood and human umbilical cord blood (CB have gained major use for treatment of hematological indications. CB, however, is also a source of cells capable of differentiating into various non-hematopoietic cell types, including neural cells. Several animal model reports have shown that CB cells may be used for treatment of neurological injuries. This review summarizes the information available on the origin of CB-derived neuronal cells and the mechanisms proposed to explain their action. The potential use of stem/progenitor cells for treatment of ischemic brain injuries is discussed. Issues that remain to be resolved at the present stage of preclinical trials are addressed.

  14. Stem cell-based approaches in dentistry

    Directory of Open Access Journals (Sweden)

    TA Mitsiadis

    2011-11-01

    Full Text Available Repair of dental pulp and periodontal lesions remains a major clinical challenge. Classical dental treatments require the use of specialised tissue-adapted materials with still questionable efficacy and durability. Stem cell-based therapeutic approaches could offer an attractive alternative in dentistry since they can promise physiologically improved structural and functional outcomes. These therapies necessitate a sufficient number of specific stem cell populations for implantation. Dental mesenchymal stem cells can be easily isolated and are amenable to in vitro expansion while retaining their stemness. In vivo studies realised in small and large animals have evidenced the potential of dental mesenchymal stem cells to promote pulp and periodontal regeneration, but have also underlined new important challenges. The homogeneity of stem cell populations and their quality control, the delivery method, the quality of the regenerated dental tissues and their integration to the host tissue are some of the key challenges. The use of bioactive scaffolds that can elicit effective tissue repair response, through activation and mobilisation of endogenous stem cell populations, constitutes another emerging therapeutic strategy. Finally, the use of stem cells and induced pluripotent cells for the regeneration of entire teeth represents a novel promising alternative to dental implant treatment after tooth loss. In this mini-review, we present the currently applied techniques in restorative dentistry and the various attempts that are made to bridge gaps in knowledge regarding treatment strategies by translating basic stem cell research into the dental practice.

  15. Influence of the extracellular matrix on endogenous and transplanted stem cells after brain damage

    Directory of Open Access Journals (Sweden)

    Lars eRoll

    2014-08-01

    Full Text Available The limited regeneration capacity of the adult central nervous system requires strategies to improve recovery of patients. In this context, the interaction of endogenous as well as transplanted stem cells with their environment is crucial. An understanding of the molecular mechanisms could help to improve regeneration by targeted manipulation.In the course of reactive gliosis, astrocytes upregulate Glial fibrillary acidic protein (GFAP and start, in many cases, to proliferate. Beside GFAP, subpopulations of these astroglial cells coexpress neural progenitor markers like Nestin. Although cells express these markers, the proportion of cells that eventually give rise to neurons is limited in many cases in vivo compared to the situation in vitro. In the first section, we present the characteristics of endogenous progenitor-like cells and discuss the differences in their neurogenic potential in vitro and in vivo.As the environment plays an important role for survival, proliferation, migration, and other processes, the second section of the review describes changes in the extracellular matrix (ECM, a complex network that contains numerous signaling molecules. It appears that signals in the damaged central nervous system lead to an activation and de-differentiation of astrocytes, but do not effectively promote neuronal differentiation of these cells. Factors that influence stem cells during development are upregulated in the damaged brain as part of an environment resembling a stem cell niche. We give a general description of the ECM composition, with focus on stem cell-associated factors like the glycoprotein Tenascin-C.Stem cell transplantation is considered as potential treatment strategy. Interaction of transplanted stem cells with the host environment is critical for the outcome of stem cell-based therapies. Possible mechanisms involving the ECM by which transplanted stem cells might improve recovery are discussed in the last section.

  16. Neural stem cells and neuro/gliogenesis in the central nervous system: understanding the structural and functional plasticity of the developing, mature, and diseased brain.

    Science.gov (United States)

    Yamaguchi, Masahiro; Seki, Tatsunori; Imayoshi, Itaru; Tamamaki, Nobuaki; Hayashi, Yoshitaka; Tatebayashi, Yoshitaka; Hitoshi, Seiji

    2016-05-01

    Neurons and glia in the central nervous system (CNS) originate from neural stem cells (NSCs). Knowledge of the mechanisms of neuro/gliogenesis from NSCs is fundamental to our understanding of how complex brain architecture and function develop. NSCs are present not only in the developing brain but also in the mature brain in adults. Adult neurogenesis likely provides remarkable plasticity to the mature brain. In addition, recent progress in basic research in mental disorders suggests an etiological link with impaired neuro/gliogenesis in particular brain regions. Here, we review the recent progress and discuss future directions in stem cell and neuro/gliogenesis biology by introducing several topics presented at a joint meeting of the Japanese Association of Anatomists and the Physiological Society of Japan in 2015. Collectively, these topics indicated that neuro/gliogenesis from NSCs is a common event occurring in many brain regions at various ages in animals. Given that significant structural and functional changes in cells and neural networks are accompanied by neuro/gliogenesis from NSCs and the integration of newly generated cells into the network, stem cell and neuro/gliogenesis biology provides a good platform from which to develop an integrated understanding of the structural and functional plasticity that underlies the development of the CNS, its remodeling in adulthood, and the recovery from diseases that affect it.

  17. The effect of incorporation of SDF-1alpha into PLGA scaffolds on stem cell recruitment and the inflammatory response.

    Science.gov (United States)

    Thevenot, Paul T; Nair, Ashwin M; Shen, Jinhui; Lotfi, Parisa; Ko, Cheng-Yu; Tang, Liping

    2010-05-01

    Despite significant advances in the understanding of tissue responses to biomaterials, most implants are still plagued by inflammatory responses which can lead to fibrotic encapsulation. This is of dire consequence in tissue engineering, where seeded cells and bioactive components are separated from the native tissue, limiting the regenerative potential of the design. Additionally, these interactions prevent desired tissue integration and angiogenesis, preventing functionality of the design. Recent evidence supports that mesenchymal stem cells (MSC) and hematopoietic stem cells (HSC) can have beneficial effects which alter the inflammatory responses and improve healing. The purpose of this study was to examine whether stem cells could be targeted to the site of biomaterial implantation and whether increasing local stem cell responses could improve the tissue response to PLGA scaffold implants. Through incorporation of SDF-1alpha through factor adsorption and mini-osmotic pump delivery, the host-derived stem cell response can be improved resulting in 3X increase in stem cell populations at the interface for up to 2 weeks. These interactions were found to significantly alter the acute mast cell responses, reducing the number of mast cells and degranulated mast cells near the scaffold implants. This led to subsequent downstream reduction in the inflammatory cell responses, and through altered mast cell activation and stem cell participation, increased angiogenesis and decreased fibrotic responses to the scaffold implants. These results support that enhanced recruitment of autologous stem cells can improve the tissue responses to biomaterial implants through modifying/bypassing inflammatory cell responses and jumpstarting stem cell participation in healing at the implant interface. Copyright 2010 Elsevier Ltd. All rights reserved.

  18. Regeneration of tracheal epithelium using mouse induced pluripotent stem cells.

    Science.gov (United States)

    Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Yoshie, Susumu; Otsuki, Koshi; Miyake, Masao; Hazama, Akihiro; Wada, Ikuo; Omori, Koichi

    2016-01-01

    Conclusion The findings demonstrated the potential use of induced pluripotent stem cells for regeneration of tracheal epithelium. Objective Autologous tissue implantation techniques using skin or cartilage are often applied in cases of tracheal defects with laryngeal inflammatory lesions and malignant tumor invasion. However, these techniques are invasive with an unstable clinical outcome. The purpose of this study was to investigate regeneration in a tracheal defect site of nude rats after implantation of ciliated epithelium that was differentiated from induced pluripotent stem cells. Method Embryoid bodies were formed from mouse induced pluripotent stem cells. They were cultured with growth factors for 5 days, and then cultured at the air-liquid interface. The degree of differentiation achieved prior to implantation was determined by histological findings and the results of real-time polymerase chain reaction. Embryoid bodies including ciliated epithelium were embedded into collagen gel that served as an artificial scaffold, and then implanted into nude rats, creating an 'air-liquid interface model'. Histological evaluation was performed 7 days after implantation. Results The ciliated epithelial structure survived on the lumen side of regenerated tissue. It was demonstrated histologically that the structure was composed of ciliated epithelial cells.

  19. Novel Regenerative Therapies Based on Regionally Induced Multipotent Stem Cells in Post-Stroke Brains: Their Origin, Characterization, and Perspective.

    Science.gov (United States)

    Takagi, Toshinori; Yoshimura, Shinichi; Sakuma, Rika; Nakano-Doi, Akiko; Matsuyama, Tomohiro; Nakagomi, Takayuki

    2017-12-01

    Brain injuries such as ischemic stroke cause severe neural loss. Until recently, it was believed that post-ischemic areas mainly contain necrotic tissue and inflammatory cells. However, using a mouse model of cerebral infarction, we demonstrated that stem cells develop within ischemic areas. Ischemia-induced stem cells can function as neural progenitors; thus, we initially named them injury/ischemia-induced neural stem/progenitor cells (iNSPCs). However, because they differentiate into more than neural lineages, we now refer to them as ischemia-induced multipotent stem cells (iSCs). Very recently, we showed that putative iNSPCs/iSCs are present within post-stroke areas in human brains. Because iNSPCs/iSCs isolated from mouse and human ischemic tissues can differentiate into neuronal lineages in vitro, it is possible that a clearer understanding of iNSPC/iSC profiles and the molecules that regulate iNSPC/iSC fate (e.g., proliferation, differentiation, and survival) would make it possible to perform neural regeneration/repair in patients following stroke. In this article, we introduce the origin and traits of iNSPCs/iSCs based on our reports and recent viewpoints. We also discuss their possible contribution to neurogenesis through endogenous and exogenous iNSPC/iSC therapies following ischemic stroke.

  20. Calcium-microRNA Complexes Functionalized Nanotubular Implant Surface for Highly Efficient Transfection and Enhanced Osteogenesis of Mesenchymal Stem Cells

    DEFF Research Database (Denmark)

    Song, Wen; Yang, Chuanxu; Svend Le, Dang Quang

    2018-01-01

    Controlling mesenchymal stem cells (MSCs) differentiation by RNA interference (RNAi) is a promising approach for next-generation regenerative medicine. However, efficient delivery of RNAi therapeutics is still a limiting factor. In this study, we have developed a simple, biocompatible and highly...... effective delivery method of small RNA therapeutics into hMSCs from an implant surface by calcium ions. First, we demonstrated that simple Ca/siGFP nanocomplexes were able to efficiently silence GFP in GFP-expressing hMSCs with adequate Ca2+ concentration (>5 mM). In addition, a single transfection could...

  1. Evaluation of quality of life in long-term survivors of paediatric brain stem tumors, treated with radiotherapy

    International Nuclear Information System (INIS)

    Skowronska-Gardas, Anna; Pedziwiatr, Katarzyna; Chojnacka, Marzanna

    2004-01-01

    The quality of life in long-term survivors of paediatric brain stem tumors, treated with radiotherapy is evaluated. They suffer predominantly from pre-treatment neurological impairments, which seriously influence their quality of life. The most often observed treatment sequelae are pituitary insufficiency and hearing loss

  2. Nop2 is expressed during proliferation of neural stem cells and in adult mouse and human brain

    Czech Academy of Sciences Publication Activity Database

    Kosi, N.; Alic, I.; Kolačevic, M.; Vrsaljko, N.; Miloševic, N.J.; Sobol, Margaryta; Filimonenko, Anatolij; Hozák, Pavel; Gajovic, S.; Pochet, R.; Mitrečic, D.

    2015-01-01

    Roč. 1597, February (2015), s. 65-76 ISSN 1872-6240 R&D Projects: GA TA ČR(CZ) TE01020118; GA MPO FR-TI3/588 Institutional support: RVO:68378050 Keywords : Nop2 * Brain * Stem cells * Stroke Subject RIV: EB - Genetics ; Molecular Biology

  3. Brain stem tumors in children - therapeutic results in patients of the University Children's Hospital of Cracow in Poland

    International Nuclear Information System (INIS)

    Korab-Chrzanowska, E.; Bartoszewska, J.; Kwiatkowski, S.

    2005-01-01

    To analyse the treatment results achieved in children treated for brain stem tumours at one institution between the years 1990 and 2004. Material. 20 patients (10 girls, 10 boys) aged 2.8-15.6 years were treated for brain stem tumors at the University Children's Hospital of Cracow (UCHC) in the years 1990-2004. The tumour type was defined basing on imaging studies (CT, MRI), and, in the case of 7 patients, additionally basing on histopathological results. In the collected material the predominant tumor type was benign glioma, detected in 17 patients. Malignant gliomas were diagnosed in 3 children. 7 children were treated by radiotherapy only. Surgical procedures and adjuvant radiotherapy were employed in 3 patients. 6 children underwent radiotherapy and chemotherapy. Combined surgical treatment followed by radiotherapy and chemotherapy was employed in 4 patients. Of the 20 patients 6 have died (30%). The surviving group (70%) includes 1 patient with tumor progression (5%), 5 - with stable tumors (25%), and 8 (40%) - with tumor regression. The probability of three-year overall survival for the entire group as calculated by the Kaplan-Meier method was 70% while the probability of three-year progression-free survival was 65%. Conclusions. Diffuse brain stem tumors, mostly those involving the pons, and malignant gliomas have poor prognosis. In the presented material we achieved the best treatment results in patients with exophytic or focal tumors, treated surgically with adjuvant therapy. (author)

  4. Clinical translation of stem cell therapy in traumatic brain injury: the potential of encapsulated mesenchymal cell biodelivery of glucagon-like peptide-1

    OpenAIRE

    Heile, Anna; Brinker, Thomas

    2011-01-01

    Traumatic brain injury remains a major cause of death and disability; it is estimated that annually 10 million people are affected. Preclinical studies have shown the potential therapeutic value of stem cell therapies. Neuroprotective as well as regenerative properties of stem cells have been suggested to be the mechanism of action in preclinical studies. However, up to now stem cell therapy has not been studied extensively in clinical trials. This article summarizes the current experimental ...

  5. Neural substrate expansion for the restoration of brain function

    Directory of Open Access Journals (Sweden)

    Han-Chiao Isaac Chen

    2016-01-01

    Full Text Available Restoring neurological and cognitive function in individuals who have suffered brain damage is one of the principal objectives of modern translational neuroscience. Electrical stimulation approaches, such as deep-brain stimulation, have achieved the most clinical success, but they ultimately may be limited by the computational capacity of the residual cerebral circuitry. An alternative strategy is brain substrate expansion, in which the computational capacity of the brain is augmented through the addition of new processing units and the reconstitution of network connectivity. This latter approach has been explored to some degree using both biological and electronic means but thus far has not demonstrated the ability to reestablish the function of large-scale neuronal networks. In this review, we contend that fulfilling the potential of brain substrate expansion will require a significant shift from current methods that emphasize direct manipulations of the brain (e.g., injections of cellular suspensions and the implantation of multi-electrode arrays to the generation of more sophisticated neural tissues and neural-electric hybrids in vitro that are subsequently transplanted into the brain. Drawing from neural tissue engineering, stem cell biology, and neural interface technologies, this strategy makes greater use of the manifold techniques available in the laboratory to create biocompatible constructs that recapitulate brain architecture and thus are more easily recognized and utilized by brain networks.

  6. CT-guided stereotaxic implantation of Ommaya reservoir for cystic brain tumor

    Energy Technology Data Exchange (ETDEWEB)

    Nakasato, Nobukazu; Niizuma, Hiroshi; Johkura, Hidefumi; Katoh, Seiya; Otsuki, Taisuke; Katakura, Ryuichi; Suzuki, Jiro

    1988-02-01

    We report the use of CT-guided stereotaxic system to implant Ommaya reservoir in 26 patients with cystic brain tumors consisting of 16 gliomas, 3 craniopharyngiomas, 3 metastatic brain tumors and 5 other and unknown pathologies, on the way of their biopsy. The entire procedure was carried out in the CT room using Leksell's CT stereotaxic system. In 24 cases with supratentorial tumors, it was at the option of the operator to take any approach such as frontal, posterior temporal and parietal approaches. Especially in 3 cases of craniopharyngioma, we inserted the tube into their cyst directly so that the ventricle should not be open to the cyst. Also in cases of a pontine glioma and a C-P angle metastatic tumor, we used retromastoid approach to the posterior fossa by making patient's heads turned about 30 to 40 deg to contralateral side of the approach, with slight flexion of the neck. Minimal bleeding occurred during operation in one case, however, it showed no clinical symptoms. Advantages of this method are as follows: Operative invasion is minimal; The surgeon can check the course of the cannula and position of the tip of Ommaya tube even at operation, and can modify it, if necessary.

  7. CT-guided stereotaxic implantation of Ommaya reservoir for cystic brain tumor

    International Nuclear Information System (INIS)

    Nakasato, Nobukazu; Niizuma, Hiroshi; Johkura, Hidefumi; Katoh, Seiya; Otsuki, Taisuke; Katakura, Ryuichi; Suzuki, Jiro

    1988-01-01

    We report the use of CT-guided stereotaxic system to implant Ommaya reservoir in 26 patients with cystic brain tumors consisting of 16 gliomas, 3 craniopharyngiomas, 3 metastatic brain tumors and 5 other and unknown pathologies, on the way of their biopsy. The entire procedure was carried out in the CT room using Leksell's CT stereotaxic system. In 24 cases with supratentorial tumors, it was at the option of the operator to take any approach such as frontal, posterior temporal and parietal approaches. Especially in 3 cases of craniopharyngioma, we inserted the tube into their cyst directly so that the ventricle should not be open to the cyst. Also in cases of a pontine glioma and a C-P angle metastatic tumor, we used retromastoid approach to the posterior fossa by making patient's heads turned about 30 to 40 deg to contralateral side of the approach, with slight flexion of the neck. Minimal bleeding occurred during operation in one case, however, it showed no clinical symptoms. Advantages of this method are as follows: Operative invasion is minimal; The surgeon can check the course of the cannula and position of the tip of Ommaya tube even at operation, and can modify it, if necessary. (author)

  8. Neuroversion: using electroconvulsive therapy as a bridge to deep brain stimulation implantation.

    Science.gov (United States)

    Williams, Nolan R; Sahlem, Greg; Pannu, Jaspreet; Takacs, Istvan; Short, Baron; Revuelta, Gonzalo; George, Mark S

    2017-02-01

    Parkinson's disease (PD) is a movement disorder with significant neuropsychiatric comorbidities. Electroconvulsive therapy (ECT) is effective in treating these neuropsychiatric symptoms; however, clinicians are reluctant to use ECT in patients with deep brain stimulation (DBS) implantations for fear of damaging the device, as well as potential cognitive side effects. Right unilateral ultra-brief pulse (RUL UBP) ECT has a more favorable cognitive side-effect profile yet has never been reported in PD patients with DBS implants. We present a case series of three patients with a history of PD that all presented with psychiatric decompensation immediately prior to planned DBS surgery. All three patients had DBS electrode(s) in place at the time and an acute course of ECT was utilized in a novel method to "bridge" these individuals to neurosurgery. The patients all experienced symptom resolution (psychosis and/or depression and/or anxiety) without apparent cognitive side effects. This case series not only illustrates that right unilateral ultra-brief pulse can be utilized in patients with DBS electrodes but also illustrates that this intervention can be utilized as a neuromodulatory "bridge", where nonoperative surgical candidates with unstable psychiatric symptoms can be converted to operative candidates in a manner similar to electrical cardioversion.

  9. Nop2 is expressed during proliferation of neural stem cells and in adult mouse and human brain

    Czech Academy of Sciences Publication Activity Database

    Kosi, N.; Alic, I.; Kolacevic, M.; Vrsaljko, N.; Milosevic, N.J.; Sobol, Margaryta; Philimonenko, Anatoly; Hozák, Pavel; Gajovic, S.; Pochet, R.; Mitrecic, D.

    2015-01-01

    Roč. 1597, FEB 9 (2015), s. 65-76 ISSN 1872-6240 R&D Projects: GA TA ČR(CZ) TE01020118; GA MPO FR-TI3/588 Institutional support: RVO:68378050 Keywords : Nop2 * Brain * Stem cells * Stroke * Nucleolus * Cell cycle Subject RIV: EB - Genetics ; Molecular Biology

  10. In vivo Brain Delivery of v-myc Overproduced Human Neural Stem Cells via the Intranasal Pathway: Tumor Characteristics in the Lung of a Nude Mouse

    Directory of Open Access Journals (Sweden)

    Eun Seong Lee

    2015-01-01

    Full Text Available We aimed to monitor the successful brain delivery of stem cells via the intranasal route and to observe the long-term consequence of the immortalized human neural stem cells in the lungs of a nude mouse model. Stably immortalized HB1.F3 human neural stem cells with firefly luciferase gene (F3-effluc were intranasally delivered to BALB/c nude mice. Bioluminescence images were serially acquired until 41 days in vivo and at 4 hours and 41 days ex vivo after intranasal delivery. Lungs were evaluated by histopathology. After intranasal delivery of F3-effluc cells, the intense in vivo signals were detected in the nasal area, migrated toward the brain areas at 4 hours (4 of 13, 30.8%, and gradually decreased for 2 days. The brain signals were confirmed by ex vivo imaging (2 of 4, 50%. In the mice with initial lung signals (4 of 9, 44.4%, the lung signals disappeared for 5 days but reappeared 2 weeks later. The intense lung signals were confirmed to originate from the tumors in the lungs formed by F3-effluc cells by ex vivo imaging and histopathology. We propose that intranasal delivery of immortalized stem cells should be monitored for their successful delivery to the brain and their tumorigenicity longitudinally.

  11. Implantation of Neural Probes in the Brain Elicits Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Evon S. Ereifej

    2018-02-01

    Full Text Available Clinical implantation of intracortical microelectrodes has been hindered, at least in part, by the perpetual inflammatory response occurring after device implantation. The neuroinflammatory response observed after device implantation has been correlated to oxidative stress that occurs due to neurological injury and disease. However, there has yet to be a definitive link of oxidative stress to intracortical microelectrode implantation. Thus, the objective of this study is to give direct evidence of oxidative stress following intracortical microelectrode implantation. This study also aims to identify potential molecular targets to attenuate oxidative stress observed postimplantation. Here, we implanted adult rats with silicon non-functional microelectrode probes for 4 weeks and compared the oxidative stress response to no surgery controls through postmortem gene expression analysis and qualitative histological observation of oxidative stress markers. Gene expression analysis results at 4 weeks postimplantation indicated that EH domain-containing 2, prion protein gene (Prnp, and Stearoyl-Coenzyme A desaturase 1 (Scd1 were all significantly higher for animals implanted with intracortical microelectrode probes compared to no surgery control animals. To the contrary, NADPH oxidase activator 1 (Noxa1 relative gene expression was significantly lower for implanted animals compared to no surgery control animals. Histological observation of oxidative stress showed an increased expression of oxidized proteins, lipids, and nucleic acids concentrated around the implant site. Collectively, our results reveal there is a presence of oxidative stress following intracortical microelectrode implantation compared to no surgery controls. Further investigation targeting these specific oxidative stress linked genes could be beneficial to understanding potential mechanisms and downstream therapeutics that can be utilized to reduce oxidative stress-mediated damage

  12. Human Mesenchymal Stem Cell Treatment Normalizes Cortical Gene Expression after Traumatic Brain Injury.

    Science.gov (United States)

    Darkazalli, Ali; Vied, Cynthia; Badger, Crystal-Dawn; Levenson, Cathy W

    2017-01-01

    Traumatic brain injury (TBI) results in a progressive disease state with many adverse and long-term neurological consequences. Mesenchymal stem cells (MSCs) have emerged as a promising cytotherapy and have been previously shown to reduce secondary apoptosis and cognitive deficits associated with TBI. Consistent with the established literature, we observed that systemically administered human MSCs (hMSCs) accumulate with high specificity at the TBI lesion boundary zone known as the penumbra. Substantial work has been done to illuminate the mechanisms by which MSCs, and the bioactive molecules they secrete, exert their therapeutic effect. However, no such work has been published to examine the effect of MSC treatment on gene expression in the brain post-TBI. In the present study, we use high-throughput RNA sequencing (RNAseq) of cortical tissue from the TBI penumbra to assess the molecular effects of both TBI and subsequent treatment with intravenously delivered hMSCs. RNAseq revealed that expression of almost 7000 cortical genes in the penumbra were differentially regulated by TBI. Pathway analysis using the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway database revealed that TBI regulated a large number of genes belonging to pathways involved in metabolism, receptor-mediated cell signaling, neuronal plasticity, immune cell recruitment and infiltration, and neurodegenerative disease. Remarkably, hMSC treatment was found to normalize 49% of all genes disrupted by TBI, with notably robust normalization of specific pathways within the categories mentioned above, including neuroactive receptor-ligand interactions (57%), glycolysis and gluconeogenesis (81%), and Parkinson's disease (100%). These data provide evidence in support of the multi-mechanistic nature of stem cell therapy and suggest that hMSC treatment is capable of simultaneously normalizing a wide variety of important molecular pathways that are disrupted by brain injury.

  13. A case of myxedema coma presenting as a brain stem infarct in a 74-year-old Korean woman.

    Science.gov (United States)

    Ahn, Ji Yun; Kwon, Hyuk-Sool; Ahn, Hee Chol; Sohn, You Dong

    2010-09-01

    Myxedema coma is the extreme form of untreated hypothyroidism. In reality, few patients present comatose with severe myxedema. We describe a patient with myxedema coma which was initially misdiagnosed as a brain stem infarct. She presented to the hospital with alteration of the mental status, generalized edema, hypothermia, hypoventilation, and hypotension. Initially her brain stem reflexes were absent. After respiratory and circulatory support, her neurologic status was not improved soon. The diagnosis of myxedema coma was often missed or delayed due to various clinical findings and concomitant medical condition and precipitating factors. It is more difficult to diagnose when a patient has no medical history of hypothyroidism. A high index of clinical suspicion can make a timely diagnosis and initiate appropriate treatment. We report this case to alert clinicians considering diagnosis of myxedema coma in patients with severe decompensated metabolic state including mental change.

  14. Fractal Interfaces for Stimulating and Recording Neural Implants

    Science.gov (United States)

    Watterson, William James

    From investigating movement in an insect to deciphering cognition in a human brain to treating Parkinson's disease, hearing loss, or even blindness, electronic implants are an essential tool for understanding the brain and treating neural diseases. Currently, the stimulating and recording resolution of these implants remains low. For instance, they can record all the neuron activity associated with movement in an insect, but are quite far from recording, at an individual neuron resolution, the large volumes of brain tissue associated with cognition. Likewise, there is remarkable success in the cochlear implant restoring hearing due to the relatively simple anatomy of the auditory nerves, but are failing to restore vision to the blind due to poor signal fidelity and transmission in stimulating the more complex anatomy of the visual nerves. The critically important research needed to improve the resolution of these implants is to optimize the neuron-electrode interface. This thesis explores geometrical and material modifications to both stimulating and recording electrodes which can improve the neuron-electrode interface. First, we introduce a fractal electrode geometry which radically improves the restored visual acuity achieved by retinal implants and leads to safe, long-term operation of the implant. Next, we demonstrate excellent neuron survival and neurite outgrowth on carbon nanotube electrodes, thus providing a safe biomaterial which forms a strong connection between the electrode and neurons. Additional preliminary evidence suggests carbon nanotubes patterned into a fractal geometry will provide further benefits in improving the electrode-neuron interface. Finally, we propose a novel implant based off field effect transistor technology which utilizes an interconnecting fractal network of semiconducting carbon nanotubes to record from thousands of neurons simutaneously at an individual neuron resolution. Taken together, these improvements have the potential to

  15. Imaging gene expression in human mesenchymal stem cells: from small to large animals

    DEFF Research Database (Denmark)

    Willmann, Jürgen K; Paulmurugan, Ramasamy; Rodriguez-Porcel, Martin

    2009-01-01

    To evaluate the feasibility of reporter gene imaging in implanted human mesenchymal stem cells (MSCs) in porcine myocardium by using clinical positron emission tomography (PET)-computed tomography (CT) scanning.......To evaluate the feasibility of reporter gene imaging in implanted human mesenchymal stem cells (MSCs) in porcine myocardium by using clinical positron emission tomography (PET)-computed tomography (CT) scanning....

  16. Halofuginone Inhibits Angiogenesis and Growth in Implanted Metastatic Rat Brain Tumor Model-an MRI Study

    Directory of Open Access Journals (Sweden)

    Rinat Abramovitch

    2004-09-01

    Full Text Available Tumor growth and metastasis depend on angiogenesis; therefore, efforts are made to develop specific angiogenic inhibitors. Halofuginone (HF is a potent inhibitor of collagen type α1(I. In solid tumor models, HF has a potent antitumor and antiangiogenic effect in vivo, but its effect on brain tumors has not yet been evaluated. By employing magnetic resonance imaging (MRI, we monitored the effect of HF on tumor progression and vascularization by utilizing an implanted malignant fibrous histiocytoma metastatic rat brain tumor model. Here we demonstrate that treatment with HF effectively and dose-dependently reduced tumor growth and angiogenesis. On day 13, HF-treated tumors were fivefold smaller than control (P < .001. Treatment with HF significantly prolonged survival of treated animals (142%; P = .001. In HF-treated rats, tumor vascularization was inhibited by 30% on day 13 and by 37% on day 19 (P < .05. Additionally, HF treatment inhibited vessel maturation (P = .03. Finally, in HF-treated rats, we noticed the appearance of a few clusters of satellite tumors, which were distinct from the primary tumor and usually contained vessel cores. This phenomenon was relatively moderate when compared to previous reports of other antiangiogenic agents used to treat brain tumors. We therefore conclude that HF is effective for treatment of metastatic brain tumors.

  17. Spatio-temporal neural stem cell behavior that leads to both perfect and imperfect structural brain regeneration in adult newts.

    Science.gov (United States)

    Urata, Yuko; Yamashita, Wataru; Inoue, Takeshi; Agata, Kiyokazu

    2018-06-14

    Adult newts can regenerate large parts of their brain from adult neural stem cells (NSCs), but how adult NSCs reorganize brain structures during regeneration remains unclear. In development, elaborate brain structures are produced under broadly coordinated regulations of embryonic NSCs in the neural tube, whereas brain regeneration entails exquisite control of the reestablishment of certain brain parts, suggesting a yet-unknown mechanism directs NSCs upon partial brain excision. Here we report that upon one-quarter excision of the adult newt ( Pleurodeles waltl ) mesencephalon, active participation of local NSCs around specific brain subregions' boundaries leads to some imperfect and some perfect brain regeneration along an individual's rostrocaudal axis. Regeneration phenotypes depend on how the wound closing occurs using local NSCs, and perfect regeneration replicates development-like processes but takes more than one year. Our findings indicate that newt brain regeneration is supported by modularity of boundary-domain NSCs with self-organizing ability in neighboring fields. © 2018. Published by The Company of Biologists Ltd.

  18. Influence of PEEK Coating on Hip Implant Stress Shielding: A Finite Element Analysis

    Directory of Open Access Journals (Sweden)

    Jesica Anguiano-Sanchez

    2016-01-01

    Full Text Available Stress shielding is a well-known failure factor in hip implants. This work proposes a design concept for hip implants, using a combination of metallic stem with a polymer coating (polyether ether ketone (PEEK. The proposed design concept is simulated using titanium alloy stems and PEEK coatings with thicknesses varying from 100 to 400 μm. The Finite Element analysis of the cancellous bone surrounding the implant shows promising results. The effective von Mises stress increases between 81 and 92% for the complete volume of cancellous bone. When focusing on the proximal zone of the implant, the increased stress transmission to the cancellous bone reaches between 47 and 60%. This increment in load transferred to the bone can influence mineral bone loss due to stress shielding, minimizing such effect, and thus prolonging implant lifespan.

  19. Myostatin genetic inactivation inhibits myogenesis by muscle-derived stem cells in vitro but not when implanted in the mdx mouse muscle

    Science.gov (United States)

    2013-01-01

    Introduction Stimulating the commitment of implanted dystrophin+ muscle-derived stem cells (MDSCs) into myogenic, as opposed to lipofibrogenic lineages, is a promising therapeutic strategy for Duchenne muscular dystrophy (DMD). Methods To examine whether counteracting myostatin, a negative regulator of muscle mass and a pro-lipofibrotic factor, would help this process, we compared the in vitro myogenic and fibrogenic capacity of MDSCs from wild-type (WT) and myostatin knockout (Mst KO) mice under various modulators, the expression of key stem cell and myogenic genes, and the capacity of these MDSCs to repair the injured gastrocnemius in aged dystrophic mdx mice with exacerbated lipofibrosis. Results Surprisingly, the potent in vitro myotube formation by WT MDSCs was refractory to modulators of myostatin expression or activity, and the Mst KO MDSCs failed to form myotubes under various conditions, despite both MDSC expressing Oct 4 and various stem cell genes and differentiating into nonmyogenic lineages. The genetic inactivation of myostatin in MDSCs was associated with silencing of critical genes for early myogenesis (Actc1, Acta1, and MyoD). WT MDSCs implanted into the injured gastrocnemius of aged mdx mice significantly improved myofiber repair and reduced fat deposition and, to a lesser extent, fibrosis. In contrast to their in vitro behavior, Mst KO MDSCs in vivo also significantly improved myofiber repair, but had few effects on lipofibrotic degeneration. Conclusions Although WT MDSCs are very myogenic in culture and stimulate muscle repair after injury in the aged mdx mouse, myostatin genetic inactivation blocks myotube formation in vitro, but the myogenic capacity is recovered in vivo under the influence of the myostatin+ host-tissue environment, presumably by reactivation of key genes originally silenced in the Mst KO MDSCs. PMID:23295128

  20. Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications.

    Science.gov (United States)

    Abou-Antoun, Tamara J; Hale, James S; Lathia, Justin D; Dombrowski, Stephen M

    2017-04-01

    Brain tumors represent some of the most malignant cancers in both children and adults. Current treatment options target the majority of tumor cells but do not adequately target self-renewing cancer stem cells (CSCs). CSCs have been reported to resist the most aggressive radiation and chemotherapies, and give rise to recurrent, treatment-resistant secondary malignancies. With advancing technologies, we now have a better understanding of the genetic, epigenetic and molecular signatures and microenvironmental influences which are useful in distinguishing between distinctly different tumor subtypes. As a result, efforts are now underway to identify and target CSCs within various tumor subtypes based on this foundation. This review discusses progress in CSC biology as it relates to targeted therapies which may be uniquely different between pediatric and adult brain tumors. Studies to date suggest that pediatric brain tumors may benefit more from genetic and epigenetic targeted therapies, while combination treatments aimed specifically at multiple molecular pathways may be more effective in treating adult brain tumors which seem to have a greater propensity towards microenvironmental interactions. Ultimately, CSC targeting approaches in combination with current clinical therapies have the potential to be more effective owing to their ability to compromise CSCs maintenance and the mechanisms which underlie their highly aggressive and deadly nature.

  1. Functional Near-Infrared Spectroscopy Brain Imaging Investigation of Phonological Awareness and Passage Comprehension Abilities in Adult Recipients of Cochlear Implants

    Science.gov (United States)

    Bisconti, Silvia; Shulkin, Masha; Hu, Xiaosu; Basura, Gregory J.; Kileny, Paul R.; Kovelman, Ioulia

    2016-01-01

    Purpose: The aim of this study was to examine how the brains of individuals with cochlear implants (CIs) respond to spoken language tasks that underlie successful language acquisition and processing. Method: During functional near-infrared spectroscopy imaging, CI recipients with hearing impairment (n = 10, mean age: 52.7 ± 17.3 years) and…

  2. Monitoring the Bystander Killing Effect of Human Multipotent Stem Cells for Treatment of Malignant Brain Tumors

    Directory of Open Access Journals (Sweden)

    Cindy Leten

    2016-01-01

    Full Text Available Tumor infiltrating stem cells have been suggested as a vehicle for the delivery of a suicide gene towards otherwise difficult to treat tumors like glioma. We have used herpes simplex virus thymidine kinase expressing human multipotent adult progenitor cells in two brain tumor models (hU87 and Hs683 in immune-compromised mice. In order to determine the best time point for the administration of the codrug ganciclovir, the stem cell distribution and viability were monitored in vivo using bioluminescence (BLI and magnetic resonance imaging (MRI. Treatment was assessed by in vivo BLI and MRI of the tumors. We were able to show that suicide gene therapy using HSV-tk expressing stem cells can be followed in vivo by MRI and BLI. This has the advantage that (1 outliers can be detected earlier, (2 GCV treatment can be initiated based on stem cell distribution rather than on empirical time points, and (3 a more thorough follow-up can be provided prior to and after treatment of these animals. In contrast to rodent stem cell and tumor models, treatment success was limited in our model using human cell lines. This was most likely due to the lack of immune components in the immune-compromised rodents.

  3. Effects of intravenous administration of bone marrow stromal stem cells on cognitive impairment of the whole-brain irradiated rat models

    International Nuclear Information System (INIS)

    Ding Weijun; Wang Jianhua; Zhu Min; Chen Baoguo; Wang Yang

    2007-01-01

    Objective: To explore the effect of intravenous infusion of bone marrow stromal stem cells(MSCs) on cognitive function of rats after whole brain irradiation. Methods: MSCs were isolated and cultured from adult rats. After Sprague-Dawly female rats were anaesthetized with chloral hydrate, their whole cerebrum was irradiated with a single dose of 20 Gy by 6 MV X-ray. Seven days after irradiation, 4 x 106 Hoechst33342-1abelled MSCs were intravenously injected into the tail vein of these rats. Four and 8 weeks after transplantation, the learning and memorizing ability was measured with the Y maze test. Immunohistochemical method was used to identify MSCs or ceils derived from MSCs in the brain. Results: The learning and memorizing ability of irradiation groups were significantly different from that of normal control group (P < 0.01). Significant improvement of cognitive impairment was observed in rats treated with MSCs at 4 and 8 weeks after transplantation as compared with the controll groups (P<0.05). This showed that the MSCs survived and were localized to the brain tissue. The number of Hoechst33342 immunohistofluorescence positive cells and double-immunostaining cells significantly decreased in 8 weeks group as compared with the 4 weeks group. Conclusion: Marrow stromal stem cells delivered to the irradiation brain tissue through intravenous route improve the cognitive impairment after whole brain irradiation. These cells may survive and differentiate in the brain tissue of irradiated rats. (authors)

  4. Brainjacking: Implant Security Issues in Invasive Neuromodulation.

    Science.gov (United States)

    Pycroft, Laurie; Boccard, Sandra G; Owen, Sarah L F; Stein, John F; Fitzgerald, James J; Green, Alexander L; Aziz, Tipu Z

    2016-08-01

    The security of medical devices is critical to good patient care, especially when the devices are implanted. In light of recent developments in information security, there is reason to be concerned that medical implants are vulnerable to attack. The ability of attackers to exert malicious control over brain implants ("brainjacking") has unique challenges that we address in this review, with particular focus on deep brain stimulation implants. To illustrate the potential severity of this risk, we identify several mechanisms through which attackers could manipulate patients if unauthorized access to an implant can be achieved. These include blind attacks in which the attacker requires no patient-specific knowledge and targeted attacks that require patient-specific information. Blind attacks include cessation of stimulation, draining implant batteries, inducing tissue damage, and information theft. Targeted attacks include impairment of motor function, alteration of impulse control, modification of emotions or affect, induction of pain, and modulation of the reward system. We also discuss the limitations inherent in designing implants and the trade-offs that must be made to balance device security with battery life and practicality. We conclude that researchers, clinicians, manufacturers, and regulatory bodies should cooperate to minimize the risk posed by brainjacking. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Effects of the pyrethroid insecticide, deltamethrin, on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice

    DEFF Research Database (Denmark)

    Rekling, J C; Theophilidis, G

    1995-01-01

    We have studied the action of deltamethrin on respiratory modulated hypoglossal motoneurons in a brain stem slice from newborn mice. Deltamethrin depolarized the hypoglossal motoneurons, increased the background synaptic noise and reduced the frequency and amplitude of current elicited action...

  6. Umbilical cord-derived mesenchymal stem cell transplantation combined with hyperbaric oxygen treatment for repair of traumatic brain injury

    Science.gov (United States)

    Zhou, Hai-xiao; Liu, Zhi-gang; Liu, Xiao-jiao; Chen, Qian-xue

    2016-01-01

    Transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for repair of traumatic brain injury has been used in the clinic. Hyperbaric oxygen (HBO) treatment has long been widely used as an adjunctive therapy for treating traumatic brain injury. UC-MSC transplantation combined with HBO treatment is expected to yield better therapeutic effects on traumatic brain injury. In this study, we established rat models of severe traumatic brain injury by pressurized fluid (2.5–3.0 atm impact force). The injured rats were then administered UC-MSC transplantation via the tail vein in combination with HBO treatment. Compared with monotherapy, aquaporin 4 expression decreased in the injured rat brain, but growth-associated protein-43 expression, calaxon-like structures, and CM-Dil-positive cell number increased. Following combination therapy, however, rat cognitive and neurological function significantly improved. UC-MSC transplantation combined with HBO therapyfor repair of traumatic brain injury shows better therapeutic effects than monotherapy and significantly promotes recovery of neurological functions. PMID:26981097

  7. Umbilical cord-derived mesenchymal stem cell transplantation combined with hyperbaric oxygen treatment for repair of traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Hai-xiao Zhou

    2016-01-01

    Full Text Available Transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs for repair of traumatic brain injury has been used in the clinic. Hyperbaric oxygen (HBO treatment has long been widely used as an adjunctive therapy for treating traumatic brain injury. UC-MSC transplantation combined with HBO treatment is expected to yield better therapeutic effects on traumatic brain injury. In this study, we established rat models of severe traumatic brain injury by pressurized fluid (2.5-3.0 atm impact force. The injured rats were then administered UC-MSC transplantation via the tail vein in combination with HBO treatment. Compared with monotherapy, aquaporin 4 expression decreased in the injured rat brain, but growth-associated protein-43 expression, calaxon-like structures, and CM-Dil-positive cell number increased. Following combination therapy, however, rat cognitive and neurological function significantly improved. UC-MSC transplantation combined with HBO therapyfor repair of traumatic brain injury shows better therapeutic effects than monotherapy and significantly promotes recovery of neurological functions.

  8. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection

    Directory of Open Access Journals (Sweden)

    Erica L. McGrath

    2017-03-01

    Full Text Available Zika virus (ZIKV infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7, to infect primary human neural stem cells (hNSCs originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection.

  9. Differential Responses of Human Fetal Brain Neural Stem Cells to Zika Virus Infection.

    Science.gov (United States)

    McGrath, Erica L; Rossi, Shannan L; Gao, Junling; Widen, Steven G; Grant, Auston C; Dunn, Tiffany J; Azar, Sasha R; Roundy, Christopher M; Xiong, Ying; Prusak, Deborah J; Loucas, Bradford D; Wood, Thomas G; Yu, Yongjia; Fernández-Salas, Ildefonso; Weaver, Scott C; Vasilakis, Nikos; Wu, Ping

    2017-03-14

    Zika virus (ZIKV) infection causes microcephaly in a subset of infants born to infected pregnant mothers. It is unknown whether human individual differences contribute to differential susceptibility of ZIKV-related neuropathology. Here, we use an Asian-lineage ZIKV strain, isolated from the 2015 Mexican outbreak (Mex1-7), to infect primary human neural stem cells (hNSCs) originally derived from three individual fetal brains. All three strains of hNSCs exhibited similar rates of Mex1-7 infection and reduced proliferation. However, Mex1-7 decreased neuronal differentiation in only two of the three stem cell strains. Correspondingly, ZIKA-mediated transcriptome alterations were similar in these two strains but significantly different from that of the third strain with no ZIKV-induced neuronal reduction. This study thus confirms that an Asian-lineage ZIKV strain infects primary hNSCs and demonstrates a cell-strain-dependent response of hNSCs to ZIKV infection. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  10. IL-6 deficiency leads to reduced metallothionein-I+II expression and increased oxidative stress in the brain stem after 6-aminonicotinamide treatment

    DEFF Research Database (Denmark)

    Penkowa, M; Hidalgo, J

    2000-01-01

    -AN-injected IL-6KO mice reactive astrocytosis and recruitment of macrophages and T-lymphocytes were clearly reduced, as were BM leukopoiesis and spleen immune reaction. Expression of MT-I+II was significantly reduced while MT-III was increased. Oxidative stress, as determined by measuring nitrated...... in brain stem gray matter areas and BM toxicity. In both normal and genetically IL-6-deficient mice (IL-6 knockout (IL-6KO) mice), the extent of astroglial degeneration/cell death in the brain stem was similar as determined from disappearance of GFAP immunoreactivity. In 6-AN-injected normal mice reactive...... tyrosine and malondialdehyde, was increased by 6-AN to a greater extent in IL-6KO mice. The blood-brain barrier to albumin was only disrupted in 6-AN-injected normal mice, which likely is due to the substantial migration of blood-derived inflammatory cells into the CNS. The present results demonstrate...

  11. Tipifarnib in Treating Young Patients With Recurrent or Progressive High-Grade Glioma, Medulloblastoma, Primitive Neuroectodermal Tumor, or Brain Stem Glioma

    Science.gov (United States)

    2013-10-07

    Childhood High-grade Cerebral Astrocytoma; Childhood Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  12. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Kathrin Hemmer

    2014-09-01

    Full Text Available Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]. iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

  13. Differential bone-forming capacity of osteogenic cells from either embryonic stem cells or bone marrow-derived mesenchymal stem cells

    NARCIS (Netherlands)

    Both, Sanne Karijn; van Apeldoorn, Aart A.; Jukes, J.M.; Englund, Mikael C.O.; Hyllner, Johan; van Blitterswijk, Clemens; de Boer, Jan

    2011-01-01

    For more than a decade, human mesenchymal stem cells (hMSCs) have been used in bone tissue-engineering research. More recently some of the focus in this field has shifted towards the use of embryonic stem cells. While it is well known that hMSCs are able to form bone when implanted subcutaneously in

  14. Coupling failure between stem and femoral component in a constrained revision total knee arthroplasty.

    LENUS (Irish Health Repository)

    Butt, Ahsan Javed

    2013-02-01

    Knee revision using constrained implants is associated with greater stresses on the implant and interface surfaces. The present report describes a case of failure of the screw coupling between the stem and the femoral component. The cause of the failure is surmised with outline of the treatment in this case with extensive femoral bone loss. Revision implant stability was augmented with the use of a cemented femoral stem, screw fixation and the metaphyseal sleeve of an S-ROM modular hip system (DePuy international Ltd).

  15. A functional study of EGFR and Notch signaling in brain cancer stem-like cells from glioblastoma multiforme (Ph.d.)

    DEFF Research Database (Denmark)

    Kristoffersen, Karina

    2013-01-01

    Glioblastoma Multiforme (GBM) is the most common and aggressive brain tumor in adults with a median survival for newly diagnosed GBM patients at less than 1.5 year. Despite intense treatment efforts the vast majority of patients will experience relapse and much research today is therefore searching...... for new molecular and cellular targets that can improve the prognosis for GBM patients. One such target is the brain cancer stem-like cells (bCSC) that are believed to be responsible for tumor initiation, progression, treatment resistance and ultimately relapse. bCSC are identified based...... on their resemblance to normal neural stem cells (NSC) and their tumorigenic potential. Like for NSC, the epidermal growth factor receptor (EGFR) and Notch receptor signaling pathways are believed to be important for the maintenance of bCSC. These pathways as such present promising targets in a future anti-bCSC GBM...

  16. Estradiol receptors mediate estradiol-induced inhibition of mitochondrial Ca^{2+} efflux in rat caudate nucleus and brain stem

    OpenAIRE

    PETROVIC, SNJEZANA; MILOSEVIC, MAJA; RISTIC-MEDIC, DANIJELA; VELICKOVIC, NATASA; DRAKULIC, DUNJA; GRKOVIC, IVANA; HORVAT, ANICA

    2015-01-01

    Our earlier studies found that in vitro estradiol modulates mitochondrial Ca2+ transport in discrete brain regions. The present study examined the role of estradiol receptors (ERs) in estradiol-induced inhibition of Ca^{2+} efflux from synaptosomal mitochondria isolated from rat caudate nuclei and brain stems. Radioactively labeled CaCl_2 (0.6?0.75 µCi ^45CaCl_{2}) was used for Ca^{2+} transport monitoring. The results revealed that in the presence of ER antagonist 7\\alpha,17ß-[9[(4,4,5,5,5-...

  17. Simultaneous recording of brain extracellular glucose, spike and local field potential in real time using an implantable microelectrode array with nano-materials

    Science.gov (United States)

    Wei, Wenjing; Song, Yilin; Fan, Xinyi; Zhang, Song; Wang, Li; Xu, Shengwei; Wang, Mixia; Cai, Xinxia

    2016-03-01

    Glucose is the main substrate for neurons in the central nervous system. In order to efficiently characterize the brain glucose mechanism, it is desirable to determine the extracellular glucose dynamics as well as the corresponding neuroelectrical activity in vivo. In the present study, we fabricated an implantable microelectrode array (MEA) probe composed of platinum electrochemical and electrophysiology microelectrodes by standard micro electromechanical system (MEMS) processes. The MEA probe was modified with nano-materials and implanted in a urethane-anesthetized rat for simultaneous recording of striatal extracellular glucose, local field potential (LFP) and spike on the same spatiotemporal scale when the rat was in normoglycemia, hypoglycemia and hyperglycemia. During these dual-mode recordings, we observed that increase of extracellular glucose enhanced the LFP power and spike firing rate, while decrease of glucose had an opposite effect. This dual mode MEA probe is capable of examining specific spatiotemporal relationships between electrical and chemical signaling in the brain, which will contribute significantly to improve our understanding of the neuron physiology.

  18. Autologous stem cell transplantation in refractory Asherman′s syndrome: A novel cell based therapy

    Directory of Open Access Journals (Sweden)

    Neeta Singh

    2014-01-01

    Full Text Available Background : There is substantial evidence that adult stem cell populations exist in human endometrium, and hence it is suggested that either endogenous endometrial stem/progenitor cells can be activated or bone marrow derived stem cells can be transplanted in the uterine cavity for endometrial regeneration in Asherman′s syndrome (AS. Aims and Objectives : The objective was to evaluate the role of sub-endometrial autologous stem cell implantation in women with refractory AS in attaining menstruation and fertility. Setting : Tertiary care referral center. DESIGN: Prospective case series. Materials and Methods : Six cases of refractory AS with failed standard treatment option of hysteroscopic adhesiolysis in the past were included. Mononuclear stem cells (MNCs were implanted in sub-endometrial zone followed by exogenous oral estrogen therapy. Endometrial thickness (ET was assessed at 3, 6, and 9 months. RESULTS: Descriptive statistics and statistical analysis of study variables was carried out using STATA version 9.0. The mean MNC count was 103.3 × 106 (±20.45 with mean CD34+ count being 203,642 (±269,274. Mean of ET (mm at 3 months (4.05 ± 1.40, 6 months (5.46 ± 1.36 and 9 months (5.48 ± 1.14 were significantly (P < 0.05 increased from pretreatment level (1.38 ± 0.39. Five out of six patients resumed menstruation. Conclusion : The autologous stem cell implantation leads to endometrial regeneration reflected by restoration of menstruation in five out of six cases. Autologous stem cell implantation is a promising novel cell based therapy for refractory AS.

  19. Gelatin promotes rapid restoration of the blood brain barrier after acute brain injury.

    Science.gov (United States)

    Kumosa, Lucas S; Zetterberg, Valdemar; Schouenborg, Jens

    2018-01-01

    Gelatin coating of brain implants is known to provide considerable benefits in terms of reduced inflammatory sequalae and long-term neuroprotective effects. However, the mechanisms for gelatin's protective role in brain injury are still unknown. To address this question, cellular and molecular markers were studied with quantitative immunohistochemical microscopy at acute (implantable devices for stimulation based therapy. Currently, this field is struggling to find solutions for reducing tissue reactions to implanted micro and nanotechnology. Prior studies have recently shown that gelatin coatings lower activation of digestive microglia and mitigate the ubiquitous loss of neurons adjacent to implanted probes, both of which impede implant function. The underlying mechanisms remain to be elucidated, however. Our findings demonstrate for the first time that gelatin has a significant effect on the BBB by promoting rapid restoration of integrity after injury. Moreover, gelatin alters microglia phenotypes and modulates gelatinase activity for up to 2weeks favoring anti-inflammation and restoration of the tissue. Given the key importance of the BBB for normal brain functions, we believe our findings have substantial significance and will be highly interesting to researchers in the biomaterial field. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  20. Beyond The Anticipatory Corpse: Medicine, Power, and the Care of the Dying: A Theoretical and Methodological Intervention into the Sociology of Brain Implant Surgery.

    Science.gov (United States)

    Hancock, Black Hawk; Morrison, Daniel R

    2016-12-01

    Drawing on and extending the Foucaultian philosophical framework that Jeffrey Bishop develops in his masterful book, The Anticipatory Corpse: Medicine, Power, and the Care of the Dying, we undertake a sociological analysis of the neurological procedure-deep brain stimulation (DBS)-which implants electrodes in the brain, powered by a pacemaker-like device, for the treatment of movement disorders. Following Bishop's work, we carry out this analysis through a two-fold strategy. First, we examine how a multidisciplinary team evaluates candidates for this implant at a major medical center. We present excerpts from an ethnographic study of the "case conference" where disease entities are presented, contested, ratified, and made objects for intervention with this technology. The case conference becomes the key site in the transition from "person-with-illness" to "person-with-brain-implant" as a team of health professionals determines a plan of action by interpreting both statistical and "quality of life" data regarding their patients. Second, this article explores these decision-making processes through Bishop's conceptualization of evidence-based medicine, which relies on statistical approaches as the ultimate authority in knowledge production and medical decisions. We then reflect on Bishop's critique of the social sciences and the methodological, analytical, and substantive ramifications that The Anticipatory Corpse can offer future sociological work. © The Author 2016. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Childhood Brain Stem Glioma Treatment

    Science.gov (United States)

    ... The tentorium separates the supratentorium from the infratentorium (right panel). The skull and meninges protect the brain and spinal cord (left panel). Brain tumors are the second most common ...

  2. Proliferation of differentiated glial cells in the brain stem

    Directory of Open Access Journals (Sweden)

    P.C. Barradas

    1998-02-01

    Full Text Available Classical studies of macroglial proliferation in muride rodents have provided conflicting evidence concerning the proliferating capabilities of oligodendrocytes and microglia. Furthermore, little information has been obtained in other mammalian orders and very little is known about glial cell proliferation and differentiation in the subclass Metatheria although valuable knowledge may be obtained from the protracted period of central nervous system maturation in these forms. Thus, we have studied the proliferative capacity of phenotypically identified brain stem oligodendrocytes by tritiated thymidine radioautography and have compared it with known features of oligodendroglial differentiation as well as with proliferation of microglia in the opossum Didelphis marsupialis. We have detected a previously undescribed ephemeral, regionally heterogeneous proliferation of oligodendrocytes expressing the actin-binding, ensheathment-related protein 2'3'-cyclic nucleotide 3'-phosphodiesterase (CNPase, that is not necessarily related to the known regional and temporal heterogeneity of expression of CNPase in cell bodies. On the other hand, proliferation of microglia tagged by the binding of Griffonia simplicifolia B4 isolectin, which recognizes an alpha-D-galactosyl-bearing glycoprotein of the plasma membrane of macrophages/microglia, is known to be long lasting, showing no regional heterogeneity and being found amongst both ameboid and differentiated ramified cells, although at different rates. The functional significance of the proliferative behavior of these differentiated cells is unknown but may provide a low-grade cell renewal in the normal brain and may be augmented under pathological conditions.

  3. Efficient and Fast Differentiation of Human Neural Stem Cells from Human Embryonic Stem Cells for Cell Therapy

    Directory of Open Access Journals (Sweden)

    Xinxin Han

    2017-01-01

    Full Text Available Stem cell-based therapies have been used for repairing damaged brain tissue and helping functional recovery after brain injury. Aberrance neurogenesis is related with brain injury, and multipotential neural stem cells from human embryonic stem (hES cells provide a great promise for cell replacement therapies. Optimized protocols for neural differentiation are necessary to produce functional human neural stem cells (hNSCs for cell therapy. However, the qualified procedure is scarce and detailed features of hNSCs originated from hES cells are still unclear. In this study, we developed a method to obtain hNSCs from hES cells, by which we could harvest abundant hNSCs in a relatively short time. Then, we examined the expression of pluripotent and multipotent marker genes through immunostaining and confirmed differentiation potential of the differentiated hNSCs. Furthermore, we analyzed the mitotic activity of these hNSCs. In this report, we provided comprehensive features of hNSCs and delivered the knowledge about how to obtain more high-quality hNSCs from hES cells which may help to accelerate the NSC-based therapies in brain injury treatment.

  4. CD44v6 regulates growth of brain tumor stem cells partially through the AKT-mediated pathway.

    Directory of Open Access Journals (Sweden)

    Mayumi Jijiwa

    Full Text Available Identification of stem cell-like brain tumor cells (brain tumor stem-like cells; BTSC has gained substantial attention by scientists and physicians. However, the mechanism of tumor initiation and proliferation is still poorly understood. CD44 is a cell surface protein linked to tumorigenesis in various cancers. In particular, one of its variant isoforms, CD44v6, is associated with several cancer types. To date its expression and function in BTSC is yet to be identified. Here, we demonstrate the presence and function of the variant form 6 of CD44 (CD44v6 in BTSC of a subset of glioblastoma multiforme (GBM. Patients with CD44(high GBM exhibited significantly poorer prognoses. Among various variant forms, CD44v6 was the only isoform that was detected in BTSC and its knockdown inhibited in vitro growth of BTSC from CD44(high GBM but not from CD44(low GBM. In contrast, this siRNA-mediated growth inhibition was not apparent in the matched GBM sample that does not possess stem-like properties. Stimulation with a CD44v6 ligand, osteopontin (OPN, increased expression of phosphorylated AKT in CD44(high GBM, but not in CD44(low GBM. Lastly, in a mouse spontaneous intracranial tumor model, CD44v6 was abundantly expressed by tumor precursors, in contrast to no detectable CD44v6 expression in normal neural precursors. Furthermore, overexpression of mouse CD44v6 or OPN, but not its dominant negative form, resulted in enhanced growth of the mouse tumor stem-like cells in vitro. Collectively, these data indicate that a subset of GBM expresses high CD44 in BTSC, and its growth may depend on CD44v6/AKT pathway.

  5. Mesenchymal Stem Cells Regulate Blood Brain Barrier Integrity in Traumatic Brain Injury Through Production of the Soluble Factor TIMP3

    Science.gov (United States)

    Menge, Tyler; Zhao, Yuhai; Zhao, Jing; Wataha, Kathryn; Geber, Michael; Zhang, Jianhu; Letourneau, Phillip; Redell, John; Shen, Li; Wang, Jing; Peng, Zhalong; Xue, Hasen; Kozar, Rosemary; Cox, Charles S.; Khakoo, Aarif Y.; Holcomb, John B.; Dash, Pramod K.; Pati, Shibani

    2013-01-01

    Mesenchymal stem cells (MCSs) have been shown to have therapeutic potential in multiple disease states associated with vascular instability including traumatic brain injury (TBI). In the present study, Tissue Inhibitor of Matrix Metalloproteinase-3 (TIMP3) is identified as the soluble factor produced by MSCs that can recapitulate the beneficial effects of MSCs on endothelial function and blood brain barrier (BBB) compromise in TBI. Attenuation of TIMP3 expression in MSCs completely abrogates the effect of MSCs on BBB permeability and stability, while intravenous administration of rTIMP3 alone can inhibit BBB permeability in TBI. Our results demonstrate that MSCs increase circulating levels of soluble TIMP3, which inhibits VEGF-A induced breakdown of endothelial AJs in vitro and in vivo. These findings elucidate a clear molecular mechanism for the effects of MSCs on the BBB in TBI, and directly demonstrate a role for TIMP3 in regulation of BBB integrity. PMID:23175708

  6. Induced Pluripotent Stem Cell-Derived Neural Cells Survive and Mature in the Nonhuman Primate Brain

    Directory of Open Access Journals (Sweden)

    Marina E. Emborg

    2013-03-01

    Full Text Available The generation of induced pluripotent stem cells (iPSCs opens up the possibility for personalized cell therapy. Here, we show that transplanted autologous rhesus monkey iPSC-derived neural progenitors survive for up to 6 months and differentiate into neurons, astrocytes, and myelinating oligodendrocytes in the brains of MPTP-induced hemiparkinsonian rhesus monkeys with a minimal presence of inflammatory cells and reactive glia. This finding represents a significant step toward personalized regenerative therapies.

  7. Postnatal Development of Brain-Derived Neurotrophic Factor (BDNF) and Tyrosine Protein Kinase B (TrkB) Receptor Immunoreactivity in Multiple Brain Stem Respiratory-Related Nuclei of the Rat

    Science.gov (United States)

    Liu, Qiuli; Wong-Riley, Margaret T.T.

    2013-01-01

    Previously, we found a transient imbalance between suppressed excitation and enhanced inhibition in the respiratory network of the rat around postnatal days (P) 12–13, a critical period when the hypoxic ventilatory response is at its weakest. The mechanism underlying the imbalance is poorly understood. Brain-derived neurotrophic factor (BDNF) and its tyrosine protein kinase B (TrkB) receptors are known to potentiate glutamatergic and attenuate gamma-aminobutyric acid (GABA)ergic neurotransmission, and BDNF is essential for respiratory development. We hypothesized that the excitation-inhibition imbalance during the critical period stemmed from a reduced expression of BDNF and TrkB at that time within respiratory-related nuclei of the brain stem. An in-depth, semiquantitative immunohistochemical study was undertaken in seven respiratory-related brain stem nuclei and one nonrespiratory nucleus in P0–21 rats. The results indicate that the expressions of BDNF and TrkB: 1) in the pre-Bötzinger complex, nucleus ambiguus, commissural and ventrolateral subnuclei of solitary tract nucleus, and retrotrapezoid nucleus/parafacial respiratory group were significantly reduced at P12, but returned to P11 levels by P14; 2) in the lateral paragigantocellular nucleus and parapyramidal region were increased from P0 to P7, but were strikingly reduced at P10 and plateaued thereafter; and 3) in the nonrespiratory cuneate nucleus showed a gentle plateau throughout the first 3 post-natal weeks, with only a slight decline of BDNF expression after P11. Thus, the significant downregulation of both BDNF and TrkB in respiratory-related nuclei during the critical period may form the basis of, or at least contribute to, the inhibitory-excitatory imbalance within the respiratory network during this time. PMID:22678720

  8. Identifying endogenous neural stem cells in the adult brain in vitro and in vivo: novel approaches.

    Science.gov (United States)

    Rueger, Maria Adele; Androutsellis-Theotokis, Andreas

    2013-01-01

    In the 1960s, Joseph Altman reported that the adult mammalian brain is capable of generating new neurons. Today it is understood that some of these neurons are derived from uncommitted cells in the subventricular zone lining the lateral ventricles, and the dentate gyrus of the hippocampus. The first area generates new neuroblasts which migrate to the olfactory bulb, whereas hippocampal neurogenesis seems to play roles in particular types of learning and memory. A part of these uncommitted (immature) cells is able to divide and their progeny can generate all three major cell types of the nervous system: neurons, astrocytes, and oligodendrocytes; these properties define such cells as neural stem cells. Although the roles of these cells are not yet clear, it is accepted that they affect functions including olfaction and learning/memory. Experiments with insults to the central nervous system also show that neural stem cells are quickly mobilized due to injury and in various disorders by proliferating, and migrating to injury sites. This suggests a role of endogenous neural stem cells in disease. New pools of stem cells are being discovered, suggesting an even more important role for these cells. To understand these cells and to coax them to contribute to tissue repair it would be very useful to be able to image them in the living organism. Here we discuss advances in imaging approaches as well as new concepts that emerge from stem cell biology with emphasis on the interface between imaging and stem cells.

  9. The 16-Year Evolution of Proximal Modular Stem Design – Eliminating Failure of Modular Junction

    Directory of Open Access Journals (Sweden)

    Thomas Tkach

    2017-10-01

    Full Text Available Background: The complexity of hip reconstruction has been and continues to be a perplexing problem with restoring leg length, femoral offset, joint stability and overall hip implant fixation. These were contributing factors that lead to the development of a novel proximal femoral component design “Apex Modular Stem” (Omni, Raynham, MA. The basic stem geometry features a straight stem with a metaphyseal fit and fill cone, a medial triangle and a modular neck junction that allows for version and offset adjustment. In recent years, there has been great concern with the use of modularity in total hip arthroplasty. The goals of this study are (1 to identify complications with the use of a proximal modular design and (2 demonstrated factors that have eliminated those complications. Methods: This is a retrospective study of a single surgeon series (Design A and Design B of using the same cementless stem and proximal modular neck body (Apex Modular Stem and Omni Mod Hip Stem from 2000 to 2016 totaling 2,125 stems. 483 stems were the Design A and 1,642 stems, were of the Design B style. Results: Design A, 483 stems were implanted between 2000 and 2004. 31 alignment pins sheared resulting in a revision rate of 6.4%. Design B, 1,642 stems have been implanted between 2004 and 2016 all by the same surgeon, with no failures of the modular junction. Conclusion: All implant devices entail a multitude of risks and benefits. The Apex Modular Stem (Design A, provided excellent fixation, minimal risk of modular junction  corrosion, and simple control of anteversion and femoral offset. The limitation was found to be the risk of the alignment pin shearing (6.4%. The pin was enlarged to make it 225% stronger in torsional resistance, and in a subsequent series of over 1,600 femoral stems in a single surgeon series, there were no pin failures over a 12 year duration.

  10. Stem cell technology using bioceramics: hard tissue regeneration towards clinical application

    Directory of Open Access Journals (Sweden)

    Hiroe Ohnishi, Yasuaki Oda and Hajime Ohgushi

    2010-01-01

    Full Text Available Mesenchymal stem cells (MSCs are adult stem cells which show differentiation capabilities toward various cell lineages. We have already used MSCs for treatments of osteoarthritis, bone necrosis and bone tumor. For this purpose, culture expanded MSCs were combined with various ceramics and then implanted. Because of rejection response to allogeneic MSC implantation, we have utilized patients' own MSCs for the treatment. Bone marrow is a good cell source of MSCs, although the MSCs also exist in adipose tissue. When comparing osteogenic differentiation of these MSCs, bone marrow MSCs show more extensive bone forming capability than adipose MSCs. Thus, the bone marrow MSCs are useful for bone tissue regeneration. However, the MSCs show limited proliferation and differentiation capabilities that hindered clinical applications in some cases. Recent advances reveal that transduction of plural transcription factors into human adult cells results in generation of new type of stem cells called induced pluripotent stem cells (iPS cells. A drawback of the iPS cells for clinical applications is tumor formation after their in vivo implantation; therefore it is difficult to use iPS cells for the treatment. To circumvent the problem, we transduced a single factor of either SOX2 or NANOG into the MSCs and found high proliferation as well as osteogenic differentiation capabilities of the MSCs. The stem cells could be combined with bioceramics for clinical applications. Here, we summarize our recent technologies using adult stem cells in viewpoints of bone tissue regeneration.

  11. In vitro model of cerebral ischemia by using brain microvascular endothelial cells derived from human induced pluripotent stem cells.

    Science.gov (United States)

    Kokubu, Yasuhiro; Yamaguchi, Tomoko; Kawabata, Kenji

    2017-04-29

    Brain-derived microvascular endothelial cells (BMECs), which play a central role in blood brain barrier (BBB), can be used for the evaluation of drug transport into the brain. Although human BMEC cell lines have already been reported, they lack original properties such as barrier integrity. Pluripotent stem cells (PSCs) can be used for various applications such as regenerative therapy, drug screening, and pathological study. In the recent study, an induction method of BMECs from PSCs has been established, making it possible to more precisely study the in vitro human BBB function. Here, using induced pluripotent stem (iPS) cell-derived BMECs, we examined the effects of oxygen-glucose deprivation (OGD) and OGD/reoxygenation (OGD/R) on BBB permeability. OGD disrupted the barrier function, and the dysfunction was rapidly restored by re-supply of the oxygen and glucose. Interestingly, TNF-α, which is known to be secreted from astrocytes and microglia in the cerebral ischemia, prevented the restoration of OGD-induced barrier dysfunction in an apoptosis-independent manner. Thus, we could establish the in vitro BBB disease model that mimics the cerebral ischemia by using iPS cell-derived BMECs. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Pulp stem cells: implication in reparative dentin formation.

    Science.gov (United States)

    Dimitrova-Nakov, Sasha; Baudry, Anne; Harichane, Yassine; Kellermann, Odile; Goldberg, Michel

    2014-04-01

    Many dental pulp stem cells are neural crest derivatives essential for lifelong maintenance of tooth functions and homeostasis as well as tooth repair. These cells may be directly implicated in the healing process or indirectly involved in cell-to-cell diffusion of paracrine messages to resident (pulpoblasts) or nonresident cells (migrating mesenchymal cells). The identity of the pulp progenitors and the mechanisms sustaining their regenerative capacity remain largely unknown. Taking advantage of the A4 cell line, a multipotent stem cell derived from the molar pulp of mouse embryo, we investigated the capacity of these pulp-derived precursors to induce in vivo the formation of a reparative dentin-like structure upon implantation within the pulp of a rodent incisor or a first maxillary molar after surgical exposure. One month after the pulp injury alone, a nonmineralized fibrous matrix filled the mesial part of the coronal pulp chamber. Upon A4 cell implantation, a mineralized osteodentin was formed in the implantation site without affecting the structure and vitality of the residual pulp in the central and distal parts of the pulp chamber. These results show that dental pulp stem cells can induce the formation of reparative dentin and therefore constitute a useful tool for pulp therapies. Finally, reparative dentin was also built up when A4 progenitors were performed by alginate beads, suggesting that alginate is a suitable carrier for cell implantation in teeth. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  13. It takes two to tango, a dance between the cells of origin and cancer stem cells in the Drosophila larval brain.

    Science.gov (United States)

    Janssens, Derek H; Lee, Cheng-Yu

    2014-04-01

    During malignant transformation the cells of origin give rise to cancer stem cells which possess the capacity to undergo limitless rounds of self-renewing division, regenerating themselves while producing more tumor cells. Within normal tissues, a limitless self-renewal capacity is unique to the stem cells, which divide asymmetrically to produce more restricted progenitors. Accumulating evidence suggests that misregulation of the self-renewal machinery in stem cell progeny can lead to tumorigenesis, but how it influences the properties of the resulting tumors remains unclear. Studies of the type II neural stem cell (neuroblast) lineages in the Drosophila larval brain have identified a regulatory cascade that promotes commitment to a progenitor cell identity by restricting their response to the self-renewal machinery. Brain tumor (Brat) and Numb initiate this cascade by asymmetrically extinguishing the activity of the self-renewal factors. Subsequently, Earmuff (Erm) and the SWI/SNF complex stably restrict the competence of the progenitor cell to respond to reactivation of self-renewal mechanisms. Together, this cascade programs the progenitor cell to undergo limited rounds of division, generating exclusive differentiated progeny. Here we review how defects in this cascade lead to tumor initiation and how inhibiting the self-renewal mechanisms may be an effective strategy to block CSC expansion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Moving the brain: Neuroimaging motivational changes of deep brain stimulation in obsessive-compulsive disorder

    NARCIS (Netherlands)

    Figee, M.

    2013-01-01

    Deep brain stimulation (DBS) is a neurosurgical technique that involves the implantation of electrodes in the brain. DBS enables electrical modulation of abnormal brain activity for treatment of neuropsychiatric disorders such as obsessive-compulsive disorder (OCD). Mrs. D. has been suffering from

  15. Induced neural stem cells achieve long-term survival and functional integration in the adult mouse brain.

    Science.gov (United States)

    Hemmer, Kathrin; Zhang, Mingyue; van Wüllen, Thea; Sakalem, Marna; Tapia, Natalia; Baumuratov, Aidos; Kaltschmidt, Christian; Kaltschmidt, Barbara; Schöler, Hans R; Zhang, Weiqi; Schwamborn, Jens C

    2014-09-09

    Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Implantable medical electronics prosthetics, drug delivery, and health monitoring

    CERN Document Server

    Khanna, Vinod Kumar

    2016-01-01

    This book is a comprehensive, interdisciplinary resource for the latest information on implantable medical devices, and is intended for graduate students studying electrical engineering, electronic instrumentation, and biomedical engineering. It is also appropriate for academic researchers, professional engineers, practicing doctors, and paramedical staff. Divided into two sections on Basic Concepts and Principles, and Applications, the first section provides an all-embracing perspective of the electronics background necessary for this work. The second section deals with pacing techniques used for the heart, brain, spinal cord, and the network of nerves that interlink the brain and spinal cord with the major organs, including ear and eye prostheses. The four main offshoots of implantable electronics, which this book discusses, are: The insertion of an implantable neural amplifier for accurate recording of neural signals for neuroengineering studies The use of implantable pulse generators for pacing the activi...

  17. The role of CXC chemokine ligand (CXCL)12-CXC chemokine receptor (CXCR)4 signalling in the migration of neural stem cells towards a brain tumour

    NARCIS (Netherlands)

    van der Meulen, A. A. E.; Biber, K.; Lukovac, S.; Balasubramaniyan, V.; den Dunnen, W. F. A.; Boddeke, H. W. G. M.; Mooij, J. J. A.

    2009-01-01

    Aims: It has been shown that neural stem cells (NSCs) migrate towards areas of brain injury or brain tumours and that NSCs have the capacity to track infiltrating tumour cells. The possible mechanism behind the migratory behaviour of NSCs is not yet completely understood. As chemokines are involved

  18. Therapeutic Potential of Umbilical Cord Blood Stem Cells on Brain Damage of a Model of Stroke

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Nikravesh

    2011-11-01

    Full Text Available Introduction: Human cord blood-derived stem cells are a rich source of stem cells as well as precursors. With regard to the researchers have focused on the therapeutic potential of stem cell in the neurological disease such as stroke, the aim of this study was the investiga-tion of the therapeutic effects of human cord blood-derived stem cells in cerebral ischemia on rat. Methods: This study was carried out on young rats. Firstly, to create a laboratory model of ischemic stroke, carotid artery of animals was occluded for 30 minutes. Then, umbilical cord blood cells were isolated and labeled using bromodeoxyuridine and 2×105 cells were injected into the experimental group via the tail vein. Rats with hypoxic condi-tions were used as a sham group. A group of animals did not receive any injection or sur-geries were used as a control. Results: Obtained results were evaluated based on behavior-al responses and immunohistochemistry, with emphasis on areas of putamen and caudate nucleus in the control, sham and experimental groups. Our results indicated that behavioral recovery was observed in the experimental group compared to the either the sham or the control group. However, histological studies demonstrated a low percent of tissue injury in the experimental group in comparison with the sham group. Conclusion: Stem cell trans-plantation is beneficial for the brain tissue reparation after hypoxic ischemic cell death.

  19. Taurine Induces Proliferation of Neural Stem Cells and Synapse Development in the Developing Mouse Brain

    Science.gov (United States)

    Shivaraj, Mattu Chetana; Marcy, Guillaume; Low, Guoliang; Ryu, Jae Ryun; Zhao, Xianfeng; Rosales, Francisco J.; Goh, Eyleen L. K.

    2012-01-01

    Taurine is a sulfur-containing amino acid present in high concentrations in mammalian tissues. It has been implicated in several processes involving brain development and neurotransmission. However, the role of taurine in hippocampal neurogenesis during brain development is still unknown. Here we show that taurine regulates neural progenitor cell (NPC) proliferation in the dentate gyrus of the developing brain as well as in cultured early postnatal (P5) hippocampal progenitor cells and hippocampal slices derived from P5 mice brains. Taurine increased cell proliferation without having a significant effect on neural differentiation both in cultured P5 NPCs as well as cultured hippocampal slices and in vivo. Expression level analysis of synaptic proteins revealed that taurine increases the expression of Synapsin 1 and PSD 95. We also found that taurine stimulates the phosphorylation of ERK1/2 indicating a possible role of the ERK pathway in mediating the changes that we observed, especially in proliferation. Taken together, our results demonstrate a role for taurine in neural stem/progenitor cell proliferation in developing brain and suggest the involvement of the ERK1/2 pathways in mediating these actions. Our study also shows that taurine influences the levels of proteins associated with synapse development. This is the first evidence showing the effect of taurine on early postnatal neuronal development using a combination of in vitro, ex-vivo and in vivo systems. PMID:22916184

  20. A Strange Case of Downward Displacement of a Deep Brain Stimulation Electrode 10 Years Following Implantation: The Gliding Movement of Snakes Theory.

    Science.gov (United States)

    Iacopino, Domenico Gerardo; Maugeri, Rosario; Giugno, Antonella; Giller, Cole A

    2015-08-01

    Despite the best efforts to ensure stereotactic precision, deep brain stimulation (DBS) electrodes can wander from their intended position after implantation. We report a case of downward electrode migration 10 years following successful implantation in a patient with Parkinson disease. A 53-year-old man with Parkinson disease underwent bilateral implantation of DBS electrodes connected to a subclavicular 2-channel pulse generator. The generator was replaced 7 years later, and a computed tomography (CT) scan confirmed the correct position of both leads. The patient developed a gradual worsening affecting his right side 3 years later, 10 years after the original implantation. A CT scan revealed displacement of the left electrode inferiorly into the pons. The new CT scans and the CT scans obtained immediately after the implantation were merged within a stereotactic planning workstation (Brainlab). Comparing the CT scans, the distal end of the electrode was in the same position, the proximal tip being significantly more inferior. The size and configuration of the coiled portions of the electrode had not changed. At implantation, the length was 27.7 cm; after 10 years, the length was 30.6 cm. These data suggests that the electrode had been stretched into its new position rather than pushed. Clinicians evaluating patients with a delayed worsening should be aware of this rare event. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. A detrimental effect of a combined chemotherapy-radiotherapy approach in children with diffuse intrinsic brain stem gliomas?

    International Nuclear Information System (INIS)

    Freeman, Carolyn R.; Kepner, Jim; Kun, Larry E.; Sanford, Robert A.; Kadota, Richard; Mandell, Lynda; Friedman, Henry

    2000-01-01

    Purpose: To compare the proportion of patients that survive at least 1 year following treatment with hyperfractionated radiotherapy (HRT) to a dose of 70.2 Gy on Pediatric Oncology Group (POG) study no. 8495 with that of patients treated with similar radiotherapy plus cisplatinum given by continuous infusion on weeks 1, 3, and 5 of radiotherapy on POG no. 9239. Methods and Materials: The eligibility criteria for the two studies were identical and included age 3 to 21 years, previously untreated tumor involving the brain stem of which two-thirds was in the pons, history less than 6 months, and clinical findings typical for diffuse intrinsic brain stem glioma, including cranial nerve deficits, long tract signs, and ataxia. The outcome of 57 patients who were treated at the 70.2 Gy dose level of POG no. 8495 between May 1986 and February 1988 was compared with that of 64 patients treated with identical radiotherapy plus cisplatinum on POG no. 9239 between June 1992 and March 1996. Results: The number of patients accrued to POG no. 9239 was determined to guarantee that the probability was at least 0.80 of correctly detecting that the 1-year survival rate exceeded that of patients on POG no. 8495 by 0.2. However, the z value for this test was -1.564, giving a p value of 0.9411. That is, there is almost sufficient evidence to conclude that survival for patients receiving HRT plus cisplatinum on POG no. 9239 was worse than that for patients receiving the same radiotherapy alone on POG no. 8495. Conclusion: The finding that patients who received cisplatinum given as a radiosensitizing agent concurrent with HRT fared less well than those receiving the same dose of HRT alone was unexpected and is clearly a cause for concern as many current protocols for patients with diffuse intrinsic brain stem gliomas call for use of chemotherapeutic and/or biological agents given concurrent with radiotherapy

  2. [Early aseptic loosening of the CF 30 femoral stem].

    Science.gov (United States)

    Kovanda, M; Havlícek, V; Hudec, J

    2007-02-01

    The CF 30 stem in combination with a cementless acetabulum was used at the First Department of Orthopedic Surgery in Brno in the years 1994 to 1995. From the second year following implantation, aseptic stem loosening was recorded. In order to find explanation of this early loosening, the authors, in cooperation with the Institute of Solid Mechanics, Mechatronics and Biomechanics, carried out the stress-strain analysis in a model system. Eighty patients (31 men and 49 women) received a cemented CF30 femoral component in 1994. Of them, 16 patients underwent revision arthroplasty, three died of causes unrelated to the surgery, and four were lost to follow-up. The final clinical and radiographic check-up was carried out in 2001. The results of a comprehensive examination were available in 57 patients with a CF30 stem. The patients were evaluated on the basis of the Harris hip score and anteroposterior radiographs of the hip. X-ray films obtained immediately after surgery and those taken at regular intervals during follow-up were compared. The following characteristics were noted: translucent lines in individual zones along the stem at the cement-bone interface; osteolysis, i. e., non-linear translucent areas, at least 5 mm long, at the cement-bone interface; and subsidence of the femoral component, i. e., migration of the stem distal to the tip of the greater trochanter. The CF 30 stem survival curve showed that aseptic stem loosening occurred from post-implantation year 2, and increased during the following years. At 6 years and 6 months, a total of 16 patients underwent revision surgery, involving reimplantation in 14 and implant removal in 2 patients. Potential causes of aseptic loosening: Polyethylene wear.However, no acetabular loosening was found in this group, although acetabular components are reported to become loose more often than femoral components. By comparison of the stem survival curves for Poldi and CF 30 stems it appeared that, at 6 years and 6 months

  3. Mesenchymal stem cells support neuronal fiber growth in an organotypic brain slice co-culture model.

    Science.gov (United States)

    Sygnecka, Katja; Heider, Andreas; Scherf, Nico; Alt, Rüdiger; Franke, Heike; Heine, Claudia

    2015-04-01

    Mesenchymal stem cells (MSCs) have been identified as promising candidates for neuroregenerative cell therapies. However, the impact of different isolation procedures on the functional and regenerative characteristics of MSC populations has not been studied thoroughly. To quantify these differences, we directly compared classically isolated bulk bone marrow-derived MSCs (bulk BM-MSCs) to the subpopulation Sca-1(+)Lin(-)CD45(-)-derived MSCs(-) (SL45-MSCs), isolated by fluorescence-activated cell sorting from bulk BM-cell suspensions. Both populations were analyzed with respect to functional readouts, that are, frequency of fibroblast colony forming units (CFU-f), general morphology, and expression of stem cell markers. The SL45-MSC population is characterized by greater morphological homogeneity, higher CFU-f frequency, and significantly increased nestin expression compared with bulk BM-MSCs. We further quantified the potential of both cell populations to enhance neuronal fiber growth, using an ex vivo model of organotypic brain slice co-cultures of the mesocortical dopaminergic projection system. The MSC populations were cultivated underneath the slice co-cultures without direct contact using a transwell system. After cultivation, the fiber density in the border region between the two brain slices was quantified. While both populations significantly enhanced fiber outgrowth as compared with controls, purified SL45-MSCs stimulated fiber growth to a larger degree. Subsequently, we analyzed the expression of different growth factors in both cell populations. The results show a significantly higher expression of brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor in the SL45-MSCs population. Altogether, we conclude that MSC preparations enriched for primary MSCs promote neuronal regeneration and axonal regrowth, more effectively than bulk BM-MSCs, an effect that may be mediated by a higher BDNF secretion.

  4. Simultaneous recording of brain extracellular glucose, spike and local field potential in real time using an implantable microelectrode array with nano-materials

    International Nuclear Information System (INIS)

    Wei, Wenjing; Song, Yilin; Fan, Xinyi; Zhang, Song; Wang, Li; Xu, Shengwei; Wang, Mixia; Cai, Xinxia

    2016-01-01

    Glucose is the main substrate for neurons in the central nervous system. In order to efficiently characterize the brain glucose mechanism, it is desirable to determine the extracellular glucose dynamics as well as the corresponding neuroelectrical activity in vivo. In the present study, we fabricated an implantable microelectrode array (MEA) probe composed of platinum electrochemical and electrophysiology microelectrodes by standard micro electromechanical system (MEMS) processes. The MEA probe was modified with nano-materials and implanted in a urethane-anesthetized rat for simultaneous recording of striatal extracellular glucose, local field potential (LFP) and spike on the same spatiotemporal scale when the rat was in normoglycemia, hypoglycemia and hyperglycemia. During these dual-mode recordings, we observed that increase of extracellular glucose enhanced the LFP power and spike firing rate, while decrease of glucose had an opposite effect. This dual mode MEA probe is capable of examining specific spatiotemporal relationships between electrical and chemical signaling in the brain, which will contribute significantly to improve our understanding of the neuron physiology. (paper)

  5. The surgical viability and radiological monitoring of brain implants of bioactive micro-seeds in an animal model

    Directory of Open Access Journals (Sweden)

    Giane X. O. Silva

    2005-10-01

    Full Text Available The interstitial implant is a therapeutic modality in brachytherapy of the head and neck. Presently, the seeds implanted in tumors in the central nervous system are metallic I-125. After the full emission of the radionuclide, the seed remains inert in the implanted area. Bioactive ceramic seeds have been prepared for this research group incorporating Sm-152 to be active in Sm-153. The main goal of the present study is the development of a the surgical technique for implanting the biodegradable radioactive micro-seeds in the brains of rabbits, as well as the observation of the clinical reactions of the animal after implantation of two sets of three seeds. The surgical procedure consisted of performing two separate perforations 10 mm from each other in the skull, permitting the implantation of two groups of three seeds, totaling six seeds. The results of the pilot study showed the effectiveness of the surgical procedure and of the biocompatibility of the seeds and the lack of presence of adverse reactions, functional sequels, or inflammation in a follow up 50 days post-surgery. Such seeds of reduced volume, 0.2 x 1.6 mm, could be monitored by computerized tomography 30 days after implanting.Os implantes intersticiais podem ser utilizados em braquiterapia de cabeça e pescoço. Atualmente as sementes implantadas no CNS são de I-125 metálicas. Após o decaimento do radioisótopo, a semente fica inerte na região implantada. Sementes cerâmicas bioativas tem sido preparadas pelo grupo de pesquisa incorporando Sm-152. O presente estudo tem o objetivo de viabilizar a técnica cirúrgica de implantes de microsementes biodegradáveis não radioativas no cérebro de coelhos, bem como verificar as reações clínicas e funcionais do animal ao corpo estranho implantado. O procedimento cirúrgico compreendeu em proceder duas perfurações separadas em 10mm na calota craniana onde foi possível a implantação de dois conjuntos de três sementes

  6. Influence of undersized cementless hip stems on primary stability and strain distribution.

    Science.gov (United States)

    Fottner, Andreas; Woiczinski, Matthias; Kistler, Manuel; Schröder, Christian; Schmidutz, Tobias F; Jansson, Volkmar; Schmidutz, Florian

    2017-10-01

    Undersizing of cementless hip stems is a risk factor for aseptic loosening and early subsidence. The purpose of this study was to evaluate the effects of undersized stems and determine whether a biomechanical study can predict the clinical results. Three consecutive sizes of a clinically proven stem (CLS Spotorno) were implanted into six composite femora (size large, Sawbones ® ), respectively. According to the Canal Fill Index (CFI), two stems (size 11.25 and 12.5) were undersized (CFI  80%). The primary stability was evaluated by measurement of 3-dimensional (3D)-micromotions under physiological adapted load and surface strains were recorded before and after implantation to detect stress-shielding processes. Both undersized stems revealed significantly higher micromotions in all regions compared to the appropriate stem. The highest micromotions were registered at the distal tip of the three stem sizes. The changes in surface strain did not show a significant difference between the three stem sizes, but the highest strain reduction was observed proximally indicating a tendency for stress shielding. This study confirms the clinical assumption that undersized stem result in a significantly reduced primary stability. Furthermore, in vitro studies allow to determine the effects of undersizing and stress shielding processes.

  7. Gefitinib Radiosensitizes Stem-Like Glioma Cells: Inhibition of Epidermal Growth Factor Receptor-Akt-DNA-PK Signaling, Accompanied by Inhibition of DNA Double-Strand Break Repair

    International Nuclear Information System (INIS)

    Kang, Khong Bee; Zhu Congju; Wong Yinling; Gao Qiuhan; Ty, Albert; Wong, Meng Cheong

    2012-01-01

    Purpose: We compared radiosensitivity of brain tumor stem cells (BTSCs) with matched nonstem glioma cells, and determined whether gefitinib enhanced BTSC radiosensitivity by inhibiting epidermal growth factor receptor (EGFR)–Akt-DNA–dependent protein kinase (DNA-PK) signaling, followed by enhanced DNA double-stand breaks (DSBs) and inhibition of DSB repair. Methods and Materials: Radiosensitivity of stem-like gliomaspheres and nonstem glioma cells (obtained at patient neurosurgical resection) were evaluated by clonogenic assays, γ-H 2 AX immunostaining and cell cycle distribution. Survival of irradiated and nonirradiated NOD-SCID mice intracranially implanted with stem-like gliomaspheres were monitored. Glioma cells treated with gefitinib, irradiation, or both were assayed for clonogenic survival, γ-H 2 AX immunostaining, DNA-PKcs expression, and phosphorylation of EGFR and Akt. Results: Stem-like gliomaspheres displayed BTSC characteristics of self-renewal; differentiation into lineages of neurons, oligodendrocytes, and astrocytes; and initiation of glioma growth in NOD-SCID mice. Irradiation dose-dependently reduced clonogenic survival, induced G 2 /M arrest and increased γ-H 2 AX immunostaining of nonstem glioma cells, but not stem-like gliomaspheres. There was no difference in survival of irradiated and nonirradiated mice implanted with stem-like gliomaspheres. The addition of gefitinib significantly inhibited clonogenic survival, increased γ-H 2 AX immunostaining, and reduced DNA-PKcs expression of irradiated stem-like gliomaspheres, without affecting irradiated-nonstem glioma cells. Gefitinib alone, and when combined with irradiation, inhibited phosphorylation of EGFR (Y1068 and Y1045) and Akt (S473) in stem-like gliomaspheres. In nonstem glioma cells, gefitinib alone inhibited EGFR Y1068 phosphorylation, with further inhibition by combined gefitinib and irradiation. Conclusions: Stem-like gliomaspheres are resistant to irradiation

  8. Gefitinib radiosensitizes stem-like glioma cells: inhibition of epidermal growth factor receptor-Akt-DNA-PK signaling, accompanied by inhibition of DNA double-strand break repair.

    Science.gov (United States)

    Kang, Khong Bee; Zhu, Congju; Wong, Yin Ling; Gao, Qiuhan; Ty, Albert; Wong, Meng Cheong

    2012-05-01

    We compared radiosensitivity of brain tumor stem cells (BTSCs) with matched nonstem glioma cells, and determined whether gefitinib enhanced BTSC radiosensitivity by inhibiting epidermal growth factor receptor (EGFR)-Akt-DNA-dependent protein kinase (DNA-PK) signaling, followed by enhanced DNA double-stand breaks (DSBs) and inhibition of DSB repair. Radiosensitivity of stem-like gliomaspheres and nonstem glioma cells (obtained at patient neurosurgical resection) were evaluated by clonogenic assays, γ-H(2)AX immunostaining and cell cycle distribution. Survival of irradiated and nonirradiated NOD-SCID mice intracranially implanted with stem-like gliomaspheres were monitored. Glioma cells treated with gefitinib, irradiation, or both were assayed for clonogenic survival, γ-H(2)AX immunostaining, DNA-PKcs expression, and phosphorylation of EGFR and Akt. Stem-like gliomaspheres displayed BTSC characteristics of self-renewal; differentiation into lineages of neurons, oligodendrocytes, and astrocytes; and initiation of glioma growth in NOD-SCID mice. Irradiation dose-dependently reduced clonogenic survival, induced G(2)/M arrest and increased γ-H(2)AX immunostaining of nonstem glioma cells, but not stem-like gliomaspheres. There was no difference in survival of irradiated and nonirradiated mice implanted with stem-like gliomaspheres. The addition of gefitinib significantly inhibited clonogenic survival, increased γ-H(2)AX immunostaining, and reduced DNA-PKcs expression of irradiated stem-like gliomaspheres, without affecting irradiated-nonstem glioma cells. Gefitinib alone, and when combined with irradiation, inhibited phosphorylation of EGFR (Y1068 and Y1045) and Akt (S473) in stem-like gliomaspheres. In nonstem glioma cells, gefitinib alone inhibited EGFR Y1068 phosphorylation, with further inhibition by combined gefitinib and irradiation. Stem-like gliomaspheres are resistant to irradiation-induced cytotoxicity, G(2)/M arrest, and DNA DSBs, compared with nonstem

  9. Gefitinib Radiosensitizes Stem-Like Glioma Cells: Inhibition of Epidermal Growth Factor Receptor-Akt-DNA-PK Signaling, Accompanied by Inhibition of DNA Double-Strand Break Repair

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Khong Bee, E-mail: dmskkb@nccs.com.sg [Brain Tumour Research Laboratory, Division of Medical Sciences, National Cancer Centre Singapore (Singapore); Zhu Congju; Wong Yinling; Gao Qiuhan; Ty, Albert; Wong, Meng Cheong [Brain Tumour Research Laboratory, Division of Medical Sciences, National Cancer Centre Singapore (Singapore)

    2012-05-01

    Purpose: We compared radiosensitivity of brain tumor stem cells (BTSCs) with matched nonstem glioma cells, and determined whether gefitinib enhanced BTSC radiosensitivity by inhibiting epidermal growth factor receptor (EGFR)-Akt-DNA-dependent protein kinase (DNA-PK) signaling, followed by enhanced DNA double-stand breaks (DSBs) and inhibition of DSB repair. Methods and Materials: Radiosensitivity of stem-like gliomaspheres and nonstem glioma cells (obtained at patient neurosurgical resection) were evaluated by clonogenic assays, {gamma}-H{sub 2}AX immunostaining and cell cycle distribution. Survival of irradiated and nonirradiated NOD-SCID mice intracranially implanted with stem-like gliomaspheres were monitored. Glioma cells treated with gefitinib, irradiation, or both were assayed for clonogenic survival, {gamma}-H{sub 2}AX immunostaining, DNA-PKcs expression, and phosphorylation of EGFR and Akt. Results: Stem-like gliomaspheres displayed BTSC characteristics of self-renewal; differentiation into lineages of neurons, oligodendrocytes, and astrocytes; and initiation of glioma growth in NOD-SCID mice. Irradiation dose-dependently reduced clonogenic survival, induced G{sub 2}/M arrest and increased {gamma}-H{sub 2}AX immunostaining of nonstem glioma cells, but not stem-like gliomaspheres. There was no difference in survival of irradiated and nonirradiated mice implanted with stem-like gliomaspheres. The addition of gefitinib significantly inhibited clonogenic survival, increased {gamma}-H{sub 2}AX immunostaining, and reduced DNA-PKcs expression of irradiated stem-like gliomaspheres, without affecting irradiated-nonstem glioma cells. Gefitinib alone, and when combined with irradiation, inhibited phosphorylation of EGFR (Y1068 and Y1045) and Akt (S473) in stem-like gliomaspheres. In nonstem glioma cells, gefitinib alone inhibited EGFR Y1068 phosphorylation, with further inhibition by combined gefitinib and irradiation. Conclusions: Stem-like gliomaspheres are

  10. Quantitative damage depth profiles in arsenic implanted HgCdTe

    Energy Technology Data Exchange (ETDEWEB)

    Lobre, C., E-mail: clement.lobre@cea.fr [CEA-Leti, MINATEC, 17 rue des Martyrs, 38054 Grenoble cedex 9 (France); Jalabert, D. [CEA-INAC/UJF-Grenoble 1 UMR-E, MINATEC, 17 rue des Martyrs, 38054 Grenoble cedex 9 (France); Vickridge, I.; Briand, E.; Benzeggouta, D. [Institut des NanoSciences de Paris, UMR 7588 du CNRS, Universite de Pierre et Marie Curie, Paris (France); Mollard, L. [CEA-Leti, MINATEC, 17 rue des Martyrs, 38054 Grenoble cedex 9 (France); Jouneau, P.H. [CEA-INAC/UJF-Grenoble 1 UMR-E, MINATEC, 17 rue des Martyrs, 38054 Grenoble cedex 9 (France); Ballet, P. [CEA-Leti, MINATEC, 17 rue des Martyrs, 38054 Grenoble cedex 9 (France)

    2013-10-15

    Rutherford backscattering experiments under channeling conditions (RBS-c) have been carried out on Hg{sub 0.77}Cd{sub 0.23}Te (MCT) layers implanted with arsenic. Accurate damage profiles have been extracted through a simple formalism for implanted and annealed layers. Quantitative damage profiles are correlated with structural defects observed by bright-field scanning transmission electron microscopy (BF-STEM) and chemical composition measured by secondary ion mass spectrometry (SIMS). Evolution of damage for increasing ion implantation fluence has been investigated by these three complementary techniques. Evidence is found of irradiation induced annealing during implantation. A fast damage recovery has been observed for post-implantation thermal anneals. In the case of an implanted layer annealed during 1 h, the damage profile, associated with arsenic concentration measurements, indicates the presence of complexes involving arsenic.

  11. Quantitative damage depth profiles in arsenic implanted HgCdTe

    International Nuclear Information System (INIS)

    Lobre, C.; Jalabert, D.; Vickridge, I.; Briand, E.; Benzeggouta, D.; Mollard, L.; Jouneau, P.H.; Ballet, P.

    2013-01-01

    Rutherford backscattering experiments under channeling conditions (RBS-c) have been carried out on Hg 0.77 Cd 0.23 Te (MCT) layers implanted with arsenic. Accurate damage profiles have been extracted through a simple formalism for implanted and annealed layers. Quantitative damage profiles are correlated with structural defects observed by bright-field scanning transmission electron microscopy (BF-STEM) and chemical composition measured by secondary ion mass spectrometry (SIMS). Evolution of damage for increasing ion implantation fluence has been investigated by these three complementary techniques. Evidence is found of irradiation induced annealing during implantation. A fast damage recovery has been observed for post-implantation thermal anneals. In the case of an implanted layer annealed during 1 h, the damage profile, associated with arsenic concentration measurements, indicates the presence of complexes involving arsenic

  12. Induced pluripotent stem cell-derived neural cells survive and mature in the nonhuman primate brain.

    Science.gov (United States)

    Emborg, Marina E; Liu, Yan; Xi, Jiajie; Zhang, Xiaoqing; Yin, Yingnan; Lu, Jianfeng; Joers, Valerie; Swanson, Christine; Holden, James E; Zhang, Su-Chun

    2013-03-28

    The generation of induced pluripotent stem cells (iPSCs) opens up the possibility for personalized cell therapy. Here, we show that transplanted autologous rhesus monkey iPSC-derived neural progenitors survive for up to 6 months and differentiate into neurons, astrocytes, and myelinating oligodendrocytes in the brains of MPTP-induced hemiparkinsonian rhesus monkeys with a minimal presence of inflammatory cells and reactive glia. This finding represents a significant step toward personalized regenerative therapies. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Effects of N+ implantation on polysaccharide and osmosis stress resistance of liquorice

    International Nuclear Information System (INIS)

    Wei Shenglin; Wu Lijun; Yu Zengliang

    2007-01-01

    In order to study the effects of N + implantation on osmosis stress resistance of plant, the experiment was taken with liquorice as plant model and 15% PEG as the osmosis stress agent. The results showed that the stem height growth of liquorice increased by 40.2% compared with controls (p + implantation parameters may be useful to increase osmosis stress resistance cultivation of liquorice and to make it mutated with ions beam implantation. (authors)

  14. Your Brain and Nervous System

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Your Brain & Nervous System KidsHealth / For Kids / Your Brain & Nervous ... The coolest wetsuit? Nope — he needs his cerebellum! Brain Stem Keeps You Breathing — and More Another brain ...

  15. Cancer stem cell hypotheses: Impact on modern molecular

    Indian Academy of Sciences (India)

    basis for the so-called cancer stem cell (CSC) hypotheses. The first exact proof of CSC ... or less equal ability for tumour regeneration and repopulation. (Nowell 1976 .... Also, there are reports that the 'stemness' (stem-like properties) of brain.

  16. Biomimetic brain tumor niche regulates glioblastoma cells towards a cancer stem cell phenotype.

    Science.gov (United States)

    Liu, Yung-Chiang; Lee, I-Chi; Chen, Pin-Yuan

    2018-05-01

    Glioblastoma (GBM) is the most malignant primary brain tumor and contains tumorigenic cancer stem cells (CSCs), which support the progression of tumor growth. The selection of CSCs and facilitation of the brain tumor niches may assist the development of novel therapeutics for GBM. Herein, hydrogel materials composed of agarose and hydroxypropyl methyl cellulose (HMC) in different concentrations were established and compared to emulate brain tumor niches and CSC microenvironments within a label-free system. Human GBM cell line, U-87 MG, was cultured on a series of HMC-agarose based culture system. Cell aggregation and spheroids formation were investigated after 4 days of culture, and 2.5% HMC-agarose based culture system demonstrated the largest spheroids number and size. Moreover, CD133 marker expression of GBM cells after 6 days of culture in 2.5% HMC-agarose based culture system was 60%, relatively higher than the control group at only 15%. Additionally, cells on 2.5% HMC-agarose based culture system show the highest chemoresistance, even at the high dose of 500 µM temozolomide for 72 h, the live cell ratio was still > 80%. Furthermore, the results also indicate that the expression of ABCG2 gene was up-regulated after culture in 2.5% HMC-agarose based culture system. Therefore, our results demonstrated that biomimetic brain tumor microenvironment may regulate GBM cells towards the CSC phenotype and expression of CSC characteristics. The microenvironment selection and spheroids formation in HMC-agarose based culture system may provide a label-free CSC selection strategy and drug testing model for future biomedical applications.

  17. Posterior brain in fetuses with open spina bifida at 11 to 13 weeks.

    Science.gov (United States)

    Lachmann, Robert; Chaoui, Rabih; Moratalla, Jose; Picciarelli, Gemma; Nicolaides, Kypros H

    2011-01-01

    To measure the changes in the posterior fossa in first-trimester fetuses with open spina bifida (OSB). The brain stem diameter and brain stem to occipital bone (BSOB) diameter were measured in stored images of the mid-sagittal view of the fetal face at 11(+0) to 13(+6) weeks from 30 fetuses with OSB and 1000 normal controls. In the control group, the brain stem and BSOB diameter increased significantly with crown-rump length (CRL) and the brain stem to BSOB ratio decreased. In the spina bifida group, the brain stem diameter was above the 95th percentile of the control group in 29 (96.7%) cases, the BSOB diameter was below the 5th percentile in 26 (86.7%) and the brain stem to BSOB ratio was above the 95th percentile in all cases. At 11 to 13 weeks the majority of fetuses with OSB have measurable abnormalities in the posterior brain.

  18. The neural stem cell fate determinant TLX promotes tumorigenesis and genesis of cells resembling glioma stem cells.

    Science.gov (United States)

    Park, Hyo-Jung; Kim, Jun-Kyum; Jeon, Hye-Min; Oh, Se-Yeong; Kim, Sung-Hak; Nam, Do-Hyun; Kim, Hyunggee

    2010-11-01

    A growing body of evidence indicates that deregulation of stem cell fate determinants is a hallmark of many types of malignancies. The neural stem cell fate determinant TLX plays a pivotal role in neurogenesis in the adult brain by maintaining neural stem cells. Here, we report a tumorigenic role of TLX in brain tumor initiation and progression. Increased TLX expression was observed in a number of glioma cells and glioma stem cells, and correlated with poor survival of patients with gliomas. Ectopic expression of TLX in the U87MG glioma cell line and Ink4a/Arf-deficient mouse astrocytes (Ink4a/Arf(-/-) astrocytes) induced cell proliferation with a concomitant increase in cyclin D expression, and accelerated foci formation in soft agar and tumor formation in in vivo transplantation assays. Furthermore, overexpression of TLX in Ink4a/Arf(-/-) astrocytes inhibited cell migration and invasion and promoted neurosphere formation and Nestin expression, which are hallmark characteristics of glioma stem cells, under stem cell culture conditions. Our results indicate that TLX is involved in glioma stem cell genesis and represents a potential therapeutic target for this type of malignancy.

  19. Decrease of Staphylococcal adhesion on surgical stainless steel after Si ion implantation

    International Nuclear Information System (INIS)

    Braceras, Iñigo; Pacha-Olivenza, Miguel A.; Calzado-Martín, Alicia; Multigner, Marta; Vera, Carolina; Broncano, Luis Labajos-; Gallardo-Moreno, Amparo M.; González-Carrasco, José Luis; Vilaboa, Nuria

    2014-01-01

    Highlights: • Si ion implantation of AISI 316LVM medical grade alloy might reduce bacterial adhesion and colonization. • Si ion implantation does not impair the attachment, viability and matrix maturation of human mesenchymal stem cells. • Nano-topography and surface chemistry changes account for the Si ion implantation induced effects. - Abstract: 316LVM austenitic stainless steel is often the material of choice on temporal musculoskeletal implants and surgical tools as it combines good mechanical properties and acceptable corrosion resistance to the physiologic media, being additionally relatively inexpensive. This study has aimed at improving the resistance to bacterial colonization of this surgical stainless steel, without compromising its biocompatibility and resistance. To achieve this aim, the effect of Si ion implantation on 316LVM has been studied. First, the effect of the ion implantation parameters (50 keV; fluence: 2.5–5 × 10 16 ions/cm 2 ; angle of incidence: 45–90°) has been assessed in terms of depth profiling of chemical composition by XPS and nano-topography evaluation by AFM. The in vitro biocompatibility of the alloy has been evaluated with human mesenchymal stem cells. Finally, bacterial adhesion of Staphylococcus epidermidis and Staphylococcus aureus on these surfaces has been assessed. Reduction of bacterial adhesion on Si implanted 316LVM is dependent on the implantation conditions as well as the features of the bacterial strains, offering a promising implantable biomaterial in terms of biocompatibility, mechanical properties and resistance to bacterial colonization. The effects of surface composition and nano-topography on bacterial adhesion, directly related to ion implantation conditions, are also discussed

  20. Decrease of Staphylococcal adhesion on surgical stainless steel after Si ion implantation

    Energy Technology Data Exchange (ETDEWEB)

    Braceras, Iñigo, E-mail: inigo.braceras@tecnalia.com [Tecnalia, Mikeletegi Pasealekua 2, 20009 Donostia-San Sebastian (Spain); CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) (Spain); Pacha-Olivenza, Miguel A. [CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) (Spain); Universidad de Extremadura, Departamento de Física Aplicada, Facultad de Ciencias, Av. Elvas s/n, 06006 Badajoz (Spain); Calzado-Martín, Alicia [Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid (Spain); CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) (Spain); Multigner, Marta [Centro Nacional de Investigaciones Metalúrgicas, CENIM-CSIC, Avda Gregorio del Amo 8, 28040 Madrid (Spain); CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) (Spain); Vera, Carolina [Tecnalia, Mikeletegi Pasealekua 2, 20009 Donostia-San Sebastian (Spain); CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) (Spain); Broncano, Luis Labajos-; Gallardo-Moreno, Amparo M. [Universidad de Extremadura, Departamento de Física Aplicada, Facultad de Ciencias, Av. Elvas s/n, 06006 Badajoz (Spain); CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) (Spain); González-Carrasco, José Luis [Centro Nacional de Investigaciones Metalúrgicas, CENIM-CSIC, Avda Gregorio del Amo 8, 28040 Madrid (Spain); CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) (Spain); Vilaboa, Nuria [Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid (Spain); CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) (Spain); and others

    2014-08-15

    Highlights: • Si ion implantation of AISI 316LVM medical grade alloy might reduce bacterial adhesion and colonization. • Si ion implantation does not impair the attachment, viability and matrix maturation of human mesenchymal stem cells. • Nano-topography and surface chemistry changes account for the Si ion implantation induced effects. - Abstract: 316LVM austenitic stainless steel is often the material of choice on temporal musculoskeletal implants and surgical tools as it combines good mechanical properties and acceptable corrosion resistance to the physiologic media, being additionally relatively inexpensive. This study has aimed at improving the resistance to bacterial colonization of this surgical stainless steel, without compromising its biocompatibility and resistance. To achieve this aim, the effect of Si ion implantation on 316LVM has been studied. First, the effect of the ion implantation parameters (50 keV; fluence: 2.5–5 × 10{sup 16} ions/cm{sup 2}; angle of incidence: 45–90°) has been assessed in terms of depth profiling of chemical composition by XPS and nano-topography evaluation by AFM. The in vitro biocompatibility of the alloy has been evaluated with human mesenchymal stem cells. Finally, bacterial adhesion of Staphylococcus epidermidis and Staphylococcus aureus on these surfaces has been assessed. Reduction of bacterial adhesion on Si implanted 316LVM is dependent on the implantation conditions as well as the features of the bacterial strains, offering a promising implantable biomaterial in terms of biocompatibility, mechanical properties and resistance to bacterial colonization. The effects of surface composition and nano-topography on bacterial adhesion, directly related to ion implantation conditions, are also discussed.

  1. Value of CSF gating for T2-weighted images of the temporal lobes and brain stem

    International Nuclear Information System (INIS)

    Enzmann, D.R.; O'Donohue, J.; Griffin, C.; Rubin, J.B.; Drace, J.; Wright, A.

    1987-01-01

    Ungated and CSF-gated long TR, long TE MR images of the temporal lobes, basal ganglia, and brain stem in health and disease were quantitatively compared. Twenty-five pair of images were evaluated for the following three parameters: signal-to-noise ratio (S/N), object contrast, and resolving power. Ungated sequences were performed in the same fashion as gated sequences for TR (TR = 2,000 msec, TE = 80 msec for ungated sequences; TR = 1,500-1,800 msec, TE = 80 msec for CSF-gated sequences). In both normal and pathologic brain tissue, the CSF-gated image was superior to the ungated image in object contrast and resolving power and equivalent in S/N. The major benefit of CSF gating was elimination of phase shift images arising from the basal cisterns and the third ventricle

  2. Exophytic pilocytic astrocytoma of the brain stem in an adult with encasement of the caudal cranial nerve complex (IX-XII): presurgical anatomical neuroimaging using MRI

    Energy Technology Data Exchange (ETDEWEB)

    Yousry, Indra; Yousry, Tarek A. [Department of Neuroradiology, Klinikum Grosshadern, Ludwig-Maximilians University, Marchioninistr. 15, 81377, Munich (Germany); Muacevic, Alexander; Olteanu-Nerbe, Vlad [Department of Neurosurgery, Klinikum Grosshadern, Ludwig-Maximilians University, Munich (Germany); Naidich, Thomas P. [Department of Radiology, Section of Neuroradiology, Mount Sinai Hospital, New York (United States)

    2004-07-01

    We describe a rare case of adult pilocytic astrocytoma in which exophytic growth from the brain stem presented as a right cerebellopontine angle mass. An initial MRI examination using T2- and T1-weighted images without and with contrast suggested the diagnosis of schwannoma. Subsequent use of 3D CISS (three-dimensional constructive interference in steady state) and T1-weighted contrast-enhanced 3D MP-RAGE (three-dimensional magnetization prepared rapid acquisition gradient echo) sequences led to the diagnosis of an exophytic brain stem tumor, documented the precise relationships of the tumor to cranial nerve VIII, revealed encasement of cranial nerves IX-XII (later confirmed intraoperatively), and provided the proper basis for planning surgical management. (orig.)

  3. Exophytic pilocytic astrocytoma of the brain stem in an adult with encasement of the caudal cranial nerve complex (IX-XII): presurgical anatomical neuroimaging using MRI

    International Nuclear Information System (INIS)

    Yousry, Indra; Yousry, Tarek A.; Muacevic, Alexander; Olteanu-Nerbe, Vlad; Naidich, Thomas P.

    2004-01-01

    We describe a rare case of adult pilocytic astrocytoma in which exophytic growth from the brain stem presented as a right cerebellopontine angle mass. An initial MRI examination using T2- and T1-weighted images without and with contrast suggested the diagnosis of schwannoma. Subsequent use of 3D CISS (three-dimensional constructive interference in steady state) and T1-weighted contrast-enhanced 3D MP-RAGE (three-dimensional magnetization prepared rapid acquisition gradient echo) sequences led to the diagnosis of an exophytic brain stem tumor, documented the precise relationships of the tumor to cranial nerve VIII, revealed encasement of cranial nerves IX-XII (later confirmed intraoperatively), and provided the proper basis for planning surgical management. (orig.)

  4. When stem cells grow old: phenotypes and mechanisms of stem cell aging

    Science.gov (United States)

    Schultz, Michael B.; Sinclair, David A.

    2016-01-01

    All multicellular organisms undergo a decline in tissue and organ function as they age. An attractive theory is that a loss in stem cell number and/or activity over time causes this decline. In accordance with this theory, aging phenotypes have been described for stem cells of multiple tissues, including those of the hematopoietic system, intestine, muscle, brain, skin and germline. Here, we discuss recent advances in our understanding of why adult stem cells age and how this aging impacts diseases and lifespan. With this increased understanding, it is feasible to design and test interventions that delay stem cell aging and improve both health and lifespan. PMID:26732838

  5. The pluripotency of hair follicle stem cells.

    Science.gov (United States)

    Hoffman, Robert M

    2006-02-01

    The hair follicle bulge area is an abundant, easily accessible source of actively growing, pluripotent adult stem cells. Nestin, a protein marker for neural stem cells, is also expressed in follicle stem cells as well as their immediate differentiated progeny. The nestin-expressing hair follicle stem cells differentiated into neurons, glial cells, keratinocytes and smooth muscle cells in vitro. Hair-follicle stem cells were implanted into the gap region of a severed sciatic nerve. The hair follicle stem cells greatly enhanced the rate of nerve regeneration and the restoration of nerve function. The follicle stem cells transdifferentiated largely into Schwann cells which are known to support neuron regrowth. Function of the rejoined sciatic nerve was measured by contraction of the gastrocnemius muscle upon electrical stimulation. After severing the tibial nerve and subsequent transplantation of hair-follicle stem cells, the transplanted mice recovered the ability to walk normally. These results suggest that hair-follicle stem cells provide an important accessible, autologous source of adult stem cells for regenerative medicine.

  6. Residual neural processng of musical sound features in adult cochlear implant users

    DEFF Research Database (Denmark)

    Timm, Lydia; Vuust, Peter; Brattico, Elvira

    2014-01-01

    setting lasting only 20 min. The presentation of stimuli did not require the participants' attention, allowing the study of the early automatic stage of feature processing in the auditory cortex. For the CI users, we obtained mismatch negativity (MMN) brain responses to five feature changes...... neural skills for music processing even in CI users who have been implanted in adolescence or adulthood. HIGHLIGHTS: -Automatic brain responses to musical feature changes reflect the limitations of central auditory processing in adult Cochlear Implant users.-The brains of adult CI users automatically...

  7. TOPICAL REVIEW: Stem cell technology using bioceramics: hard tissue regeneration towards clinical application

    Science.gov (United States)

    Ohnishi, Hiroe; Oda, Yasuaki; Ohgushi, Hajime

    2010-02-01

    Mesenchymal stem cells (MSCs) are adult stem cells which show differentiation capabilities toward various cell lineages. We have already used MSCs for treatments of osteoarthritis, bone necrosis and bone tumor. For this purpose, culture expanded MSCs were combined with various ceramics and then implanted. Because of rejection response to allogeneic MSC implantation, we have utilized patients' own MSCs for the treatment. Bone marrow is a good cell source of MSCs, although the MSCs also exist in adipose tissue. When comparing osteogenic differentiation of these MSCs, bone marrow MSCs show more extensive bone forming capability than adipose MSCs. Thus, the bone marrow MSCs are useful for bone tissue regeneration. However, the MSCs show limited proliferation and differentiation capabilities that hindered clinical applications in some cases. Recent advances reveal that transduction of plural transcription factors into human adult cells results in generation of new type of stem cells called induced pluripotent stem cells (iPS cells). A drawback of the iPS cells for clinical applications is tumor formation after their in vivo implantation; therefore it is difficult to use iPS cells for the treatment. To circumvent the problem, we transduced a single factor of either SOX2 or NANOG into the MSCs and found high proliferation as well as osteogenic differentiation capabilities of the MSCs. The stem cells could be combined with bioceramics for clinical applications. Here, we summarize our recent technologies using adult stem cells in viewpoints of bone tissue regeneration.

  8. Calcium-dependent plateau potentials in rostral ambiguus neurons in the newborn mouse brain stem in vitro

    DEFF Research Database (Denmark)

    Rekling, J C; Feldman, J L

    1997-01-01

    Calcium-dependent plateau potentials in rostral ambiguus neurons in the newborn mouse brain stem in vitro. J. Neurophysiol. 78: 2483-2492, 1997. The nucleus ambiguus contains vagal and glossopharyngeal motoneurons and preganglionic neurons involved in respiration, swallowing, vocalization......-stimulus orthodromic activation, using an electrode placed in the dorsomedial slice near the nucleus tractus solitarius, evoked single excitatory postsynaptic potentials (EPSPs) or short trains of EPSPs (500 ms to 1 s). However, tetanic stimulation (5 pulses, 10 Hz) induced voltage-dependent afterdepolarizations...

  9. Destiny of autologous bone marrow-derived stromal cells implanted in the vocal fold.

    Science.gov (United States)

    Kanemaru, Shin-ichi; Nakamura, Tatsuo; Yamashita, Masaru; Magrufov, Akhmar; Kita, Tomoko; Tamaki, Hisanobu; Tamura, Yoshihiro; Iguchi, Fuku-ichiro; Kim, Tae Soo; Kishimoto, Masanao; Omori, Koichi; Ito, Juichi

    2005-12-01

    The aim of this study was to investigate the destiny of implanted autologous bone marrow-derived stromal cells (BSCs) containing mesenchymal stem cells. We previously reported the successful regeneration of an injured vocal fold through implantation of BSCs in a canine model. However, the fate of the implanted BSCs was not examined. In this study, implanted BSCs were traced in order to determine the type of tissues resulting at the injected site of the vocal fold. After harvest of bone marrow from the femurs of green fluorescent transgenic mice, adherent cells were cultured and selectively amplified. By means of a fluorescence-activated cell sorter, it was confirmed that some cells were strongly positive for mesenchymal stem cell markers, including CD29, CD44, CD49e, and Sca-1. These cells were then injected into the injured vocal fold of a nude rat. Immunohistologic examination of the resected vocal folds was performed 8 weeks after treatment. The implanted cells were alive in the host tissues and showed positive expression for keratin and desmin, markers for epithelial tissue and muscle, respectively. The implanted BSCs differentiated into more than one tissue type in vivo. Cell-based tissue engineering using BSCs may improve the quality of the healing process in vocal fold injuries.

  10. Single-Cell Transcriptomics Reveals a Population of Dormant Neural Stem Cells that Become Activated upon Brain Injury.

    Science.gov (United States)

    Llorens-Bobadilla, Enric; Zhao, Sheng; Baser, Avni; Saiz-Castro, Gonzalo; Zwadlo, Klara; Martin-Villalba, Ana

    2015-09-03

    Heterogeneous pools of adult neural stem cells (NSCs) contribute to brain maintenance and regeneration after injury. The balance of NSC activation and quiescence, as well as the induction of lineage-specific transcription factors, may contribute to diversity of neuronal and glial fates. To identify molecular hallmarks governing these characteristics, we performed single-cell sequencing of an unbiased pool of adult subventricular zone NSCs. This analysis identified a discrete, dormant NSC subpopulation that already expresses distinct combinations of lineage-specific transcription factors during homeostasis. Dormant NSCs enter a primed-quiescent state before activation, which is accompanied by downregulation of glycolytic metabolism, Notch, and BMP signaling and a concomitant upregulation of lineage-specific transcription factors and protein synthesis. In response to brain ischemia, interferon gamma signaling induces dormant NSC subpopulations to enter the primed-quiescent state. This study unveils general principles underlying NSC activation and lineage priming and opens potential avenues for regenerative medicine in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Effect of Mobile Phone-Induced Electromagnetic Field on Brain Hemodynamics and Human Stem Cell Functioning: Possible Mechanistic Link to Cancer Risk and Early Diagnostic Value of Electronphotonic Imaging.

    Science.gov (United States)

    Bhargav, Hemant; Srinivasan, T M; Varambally, S; Gangadhar, B N; Koka, Prasad

    2015-01-01

    The mobile phones (MP) are low power radio devices which work on electromagnetic fields (EMFs), in the frequency range of 900-1800 MHz. Exposure to MPEMFs may affect brain physiology and lead to various health hazards including brain tumors. Earlier studies with positron emission tomography (PET) have found alterations in cerebral blood flow (CBF) after acute exposure to MPEMFs. It is widely accepted that DNA double-strand breaks (DSBs) and their misrepair in stem cells are critical events in the multistage origination of various leukemia and tumors, including brain tumors such as gliomas. Both significant misbalance in DSB repair and severe stress response have been triggered by MPEMFs and EMFs from cell towers. It has been shown that stem cells are most sensitive to microwave exposure and react to more frequencies than do differentiated cells. This may be important for cancer risk assessment and indicates that stem cells are the most relevant cellular model for validating safe mobile communication signals. Recently developed technology for recording the human bio-electromagnetic (BEM) field using Electron photonic Imaging (EPI) or Gas Discharge Visualisation (GDV) technique provides useful information about the human BEM. Studies have recorded acute effects of Mobile Phone Electromagnetic Fields (MPEMFs) using EPI and found quantifiable effects on human BEM field. Present manuscript reviews evidences of altered brain physiology and stem cell functioning due to mobile phone/cell tower radiations, its association with increased cancer risk and explores early diagnostic value of EPI imaging in detecting EMF induced changes on human BEM.

  12. Engineered Protein Coatings to Improve the Osseointegration of Dental and Orthopaedic Implants

    Science.gov (United States)

    Raphel, Jordan; Karlsson, Johan; Galli, Silvia; Wennerberg, Ann; Lindsay, Christopher; Haugh, Matthew; Pajarinen, Jukka; Goodman, Stuart B.; Jimbo, Ryo; Andersson, Martin; Heilshorn, Sarah C.

    2016-01-01

    Here we present the design of an engineered, elastin-like protein (ELP) that is chemically modified to enable stable coatings on the surfaces of titanium-based dental and orthopaedic implants by novel photocrosslinking and solution processing steps. The ELP includes an extended RGD sequence to confer bio-signaling and an elastin-like sequence for mechanical stability. ELP thin films were fabricated on cp-Ti and Ti6Al4V surfaces using scalable spin and dip coating processes with photoactive covalent crosslinking through a carbene insertion mechanism. The coatings withstood procedures mimicking dental screw and hip replacement stem implantations, a key metric for clinical translation. They promoted rapid adhesion of MG63 osteoblast-like cells, with over 80% adhesion after 24 hours, compared to 38% adhesion on uncoated Ti6Al4V. MG63 cells produced significantly more mineralization on ELP coatings compared to uncoated Ti6Al4V. Human bone marrow mesenchymal stem cells (hMSCs) had an earlier increase in alkaline phosphatase activity, indicating more rapid osteogenic differentiation and mineral deposition on adhesive ELP coatings. Rat tibia and femur in vivo studies demonstrated that cell-adhesive ELP-coated implants increased bone-implant contact area and interfacial strength after one week. These results suggest that ELP coatings withstand surgical implantation and promote rapid osseointegration, enabling earlier implant loading and potentially preventing micromotion that leads to aseptic loosening and premature implant failure. PMID:26790146

  13. Design of a Small Modified Minkowski Fractal Antenna for Passive Deep Brain Stimulation Implants

    Directory of Open Access Journals (Sweden)

    Sara Manafi

    2014-01-01

    Full Text Available A small planar modified Minkowski fractal antenna is designed and simulated in dual frequency bands (2.4 and 5.8 GHz for wireless energy harvesting by deep brain stimulation (DBS devices. The designed antenna, physically being confined inside a miniaturized structure, can efficiently convert the wireless signals in dual ISM frequency bands to the energy source to recharge the DBS battery or power the pulse generator directly. The performance metrics such as the return loss, the specific absorption rate (SAR, and the radiation pattern within skin and muscle-fat-skin tissues are evaluated for the designed antenna. The gain of the proposed antenna is 3.2 dBi at 2.4 GHz and 4.7 dBi at 5.8 GHz; also the averaged SAR of the antenna in human body tissue is found to be well below the legally allowed limit at both frequency bands. The link budget shows the received power at the distance of 25 cm at 2.4 GHz and 5.8 GHz are around 0.4 mW and 0.04 mW, which can empower the DBS implant. The large operational bandwidth, the physical compactness, and the efficiency in wireless signal reception make this antenna suitable in being used in implanted biomedical devices such as DBS pulse generators.

  14. Neurogenesis and brain injury: managing a renewable resource for repair

    OpenAIRE

    Hallbergson, Anna F.; Gnatenco, Carmen; Peterson, Daniel A.

    2003-01-01

    The brain shows limited ability to repair itself, but neurogenesis in certain areas of the adult brain suggests that neural stem cells may be used for structural brain repair. It will be necessary to understand how neurogenesis in the adult brain is regulated to develop strategies that harness neural stem cells for therapeutic use.

  15. Analysis of metallic traces from the biodegradation of endomedullary AZ31 alloy temporary implants in rat organs after long implantation times.

    Science.gov (United States)

    Bodelón, O G; Iglesias, C; Garrido, J; Clemente, C; Garcia-Alonso, M C; Escudero, M L

    2015-08-04

    AZ31 alloy has been tested as a biodegradable material in the form of endomedullary implants in female Wistar rat femurs. In order to evaluate the accumulation of potentially toxic elements from the biodegradation of the implant, magnesium (Mg), aluminium (Al), zinc (Zn), manganese (Mn) and fluorine (F) levels have been measured in different organs such as kidneys, liver, lungs, spleen and brain. Several factors that may influence accumulation have been taken into account: how long the implant has been in place, whether or not the bone is fractured, and the presence of an MgF2 protective coating on the implant. The main conclusions and the clinical relevance of the study have been that AZ31 endomedullary implants have a degradation rate of about 60% after 13 months, which is fully compatible with fracture consolidation. Neither bone fracture nor an MgF2 coating seems to influence the accumulation of trace elements in the studied organs. Aluminium is the only alloying element in this study that requires special attention. The increase in Al recovered from the sampled organs represents 3.95% of the amount contained in the AZ31 implant. Al accumulates in a statistically significant way in all the organs except the brain. All of this suggests that in long-term tests AZ31 may be a suitable material for osteosynthesis.

  16. Chondrocytic Potential of Allogenic Mesenchymal Stem Cells Transplanted without Immunosuppression to Regenerate Physeal Defect in Rabbits

    Directory of Open Access Journals (Sweden)

    P. Gál

    2007-01-01

    Full Text Available Mesenchymal stem cells (MSCs from bone marrow are multipotent cells capable of forming cartilage, bone, and other connective tissues. The objective of this study was to determine whether the use of allogenic mesenchymal stem cells could functionally heal a defect in the distal femoral physis in rabbits without the use of immunosuppressive therapy. A iatrogenic defect was created in the lateral femoral condyle of thirty-two New Zealand white rabbits, 7 weeks old, weighing 2.25 ± 0.24 kg. Each defect, 3.5 mm in width and 12 mm in length, in the right distal femoral physis was treated with allogenic mesenchymal stem cells in new composite hyaluronate/collagen type I/fibrin scaffold. The healing response was evaluated radiographically, by MRI (three weeks and four months after implantation and also histologically, by Pearl’s reaction and with immunofluorescence (four months after implantation. The results were compared with the data for the control defects (without stem cell implantation in left distal femoral physes. On average, right femurs with a damaged distal physis and transplanted MSCs grew more in length (0.55 ± 0.21 cm compared with left femurs with a physeal defect without stem cell transplantation (0.46 ± 0.23 cm. Valgus deformity of right femurs with a physeal defect and transplanted MSCs was mild (0.2 ± 0.1 °. On the contrary, left femurs with a physeal defect without transplanted MSCs showed a significant valgus deformity (2.7 ± 1.6 °. For defects treated with allogenic mesenchymal stem cell implants, no adverse immune response and implant rejection were detected in this model. Histologically, no lymphocytic infiltration occurred. At four months after transplantation, hyaline cartilage had formed throughout the defects treated with allogenic MSCs. Labelled mesenchymal stem cells/differentiated chondrocytes were detected in the physeal defects based on magnetic resonance imaging and immunofluorescence. The results of this study

  17. Hydroxyapatite coating does not improve uncemented stem survival after total hip arthroplasty!

    DEFF Research Database (Denmark)

    Hailer, N. P.; Lazarinis, S.; MaKela, K. T.

    2015-01-01

    Background and purpose - It is still being debated whether HA coating of uncemented stems used in total hip arthroplasty (THA) improves implant survival. We therefore investigated different uncemented stem brands, with and without HA coating, regarding early and long-term survival. Patients and m...

  18. A Chronically Implantable Bidirectional Neural Interface for Non-human Primates

    Directory of Open Access Journals (Sweden)

    Misako Komatsu

    2017-09-01

    Full Text Available Optogenetics has potential applications in the study of epilepsy and neuroprostheses, and for studies on neural circuit dynamics. However, to achieve translation to clinical usage, optogenetic interfaces that are capable of chronic stimulation and monitoring with minimal brain trauma are required. We aimed to develop a chronically implantable device for photostimulation of the brain of non-human primates. We used a micro-light-emitting diode (LED array with a flexible polyimide film. The array was combined with a whole-cortex electrocorticographic (ECoG electrode array for simultaneous photostimulation and recording. Channelrhodopsin-2 (ChR2 was virally transduced into the cerebral cortex of common marmosets, and then the device was epidurally implanted into their brains. We recorded the neural activity during photostimulation of the awake monkeys for 4 months. The neural responses gradually increased after the virus injection for ~8 weeks and remained constant for another 8 weeks. The micro-LED and ECoG arrays allowed semi-invasive simultaneous stimulation and recording during long-term implantation in the brains of non-human primates. The development of this device represents substantial progress in the field of optogenetic applications.

  19. Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

    International Nuclear Information System (INIS)

    Evers, Patrick; Lee, Percy P; DeMarco, John; Agazaryan, Nzhde; Sayre, James W; Selch, Michael; Pajonk, Frank

    2010-01-01

    Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs

  20. Extensively coated revision stems in proximally deficient femur: Early results in 15 patients

    Directory of Open Access Journals (Sweden)

    Marya SKS

    2008-01-01

    Full Text Available Background: Hip replacement following failed internal fixation (dynamic hip screw for intertrochanteric fractures or previous hip arthroplasty presents a major surgical challenge. Proximal fitting revision stems do not achieve adequate fixation. Distal fixation with long-stemmed extensively coated cementless implants (like the Solution™ system affords a suitable solution. We present our early results of 15 patients treated with extensively coated cementless revision stems. Materials and Methods: Fifteen patients with severely compromised proximal femora following either failed hip arthroplasty or failed internal fixation (dynamic hip screw fixation for intertrochanteric fractures were operated by the senior author over a two-year period. Eight patients had aseptic loosening of their femoral stems following cemented hip replacements, with severe thinning of their proximal cortices and impending stress fractures. Seven had secondary hip arthritis following failure of long implants for comminuted intertrochanteric or subtrochanteric femoral fractures. All patients were treated by removal of implant (cemented stems/DHS implants and insertion of long-stemmed extensively coated cementless revision (′ Solution™; DePuy, Warsaw (IN, US′ stems along with press-fit acetabular component (Duraloc Cup, DePuy, Warsaw (IN, US. All eight hip revisions needed extended trochanteric osteotomies. Results: All patients were primarily kept in bed on physiotherapy for six weeks and then gradually progressed to weight-bearing walking over the next six to eight weeks. The Harris Hip Scores and patient satisfaction were used for final evaluation. We achieved good results in the short term studied. In our first three patients (all following failed cemented total hip replacements, we resorted to cerclage wiring to hold osteotomised segments (done to facilitate stem removal. The subsequent 12 proceeded without the need for cerclage wiring. One patient had a

  1. Cancer stem cells in head and neck cancer

    Directory of Open Access Journals (Sweden)

    Trapasso S

    2012-11-01

    Full Text Available Eugenia Allegra, Serena TrapassoOtolaryngology – Head and Neck Surgery, University Magna Graecia of Catanzaro, Catanzaro, ItalyAbstract: Cancer stem cells (CSCs, also called "cells that start the tumor," represent in themselves one of the most topical and controversial issues in the field of cancer research. Tumor stem cells are able to self-propagate in vitro (self-renewal, giving rise both to other tumor stem cells and most advanced cells in the line of differentiation (asymmetric division. A final characteristic is tumorigenicity, a fundamental property, which outlines the tumor stem cell as the only cell able to initiate the formation of a tumor when implanted in immune-deficient mice. The hypothesis of a hierarchical organization of tumor cells dates back more than 40 years, but only in 1997, thanks to the work of John Dick and Dominique Bonnet, was there the formal proof of such an organization in acute myeloid leukemia. Following this, many other research groups were able to isolate CSCs, by appropriate selection markers, in various malignancies, such as breast, brain, colon, pancreas, and liver cancers and in melanoma. To date, however, it is not possible to isolate stem cells from all types of neoplasia, particularly in solid tumors. From a therapeutic point of view, the concept of tumor stem cells implies a complete revision of conventional antineoplastic treatment. Conventional cytotoxic agents are designed to target actively proliferating cells. In the majority of cases, this is not sufficient to eliminate the CSCs, which thanks to their reduced proliferative activity and/or the presence of proteins capable of extruding chemotherapeutics from the cell are not targeted. Therefore, the theory of cancer stem cells can pose new paradigms in terms of cancer treatment. Potential approaches, even in the very early experimental stages, relate to the selective inhibition of pathways connected with self-renewal, or more specifically based on

  2. Short uncemented stems allow greater femoral flexibility and may reduce peri-prosthetic fracture risk: a dry bone and cadaveric study.

    Science.gov (United States)

    Jones, Christopher; Aqil, Adeel; Clarke, Susannah; Cobb, Justin P

    2015-09-01

    Short femoral stems for uncemented total hip arthroplasty have been introduced as a safe alternative to traditional longer stem designs. However, there has been little biomechanical examination of the effects of stem length on complications of surgery. This study aims to examine the effect of femoral stem length on torsional resistance to peri-prosthetic fracture. We tested 16 synthetic and two paired cadaveric femora. Specimens were implanted and then rapidly rotated until fracture to simulate internal rotation on a planted foot, as might occur during stumbling. 3D planning software and custom-printed 3D cutting guides were used to enhance the accuracy and consistency of our stem insertion technique. Synthetic femora implanted with short stems fractured at a significantly higher torque (27.1 vs. 24.2 Nm, p = 0.03) and angle (30.3° vs. 22.3°, p = 0.002) than those implanted with long stems. Fracture patterns of the two groups were different, but showed remarkable consistency within each group. These characteristic fracture patterns were closely replicated in the pair of cadaveric femora. This new short-stemmed press-fit femoral component allows more femoral flexibility and confers a higher resistance to peri-prosthetic fracture from torsional forces than long stems.

  3. When stem cells grow old: phenotypes and mechanisms of stem cell aging.

    Science.gov (United States)

    Schultz, Michael B; Sinclair, David A

    2016-01-01

    All multicellular organisms undergo a decline in tissue and organ function as they age. An attractive theory is that a loss in stem cell number and/or activity over time causes this decline. In accordance with this theory, aging phenotypes have been described for stem cells of multiple tissues, including those of the hematopoietic system, intestine, muscle, brain, skin and germline. Here, we discuss recent advances in our understanding of why adult stem cells age and how this aging impacts diseases and lifespan. With this increased understanding, it is feasible to design and test interventions that delay stem cell aging and improve both health and lifespan. © 2016. Published by The Company of Biologists Ltd.

  4. Bilateral cerebellar and brain stem infarction resulting from vertebral artery injury following cervical trauma without radiographic damage of the spinal column: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Mimata, Yoshikuni; Sato, Kotaro; Suzuki, Yoshiaki [Iwate Prefectural Chubu Hospital, Department of Orthopaedic Surgery, Kitakami (Japan); Murakami, Hideki [Iwate Medical University, Department of Orthopaedic Surgery, School of Medicine, Morioka (Japan)

    2014-01-15

    Vertebral artery injury can be a complication of cervical spine injury. Although most cases are asymptomatic, the rare case progresses to severe neurological impairment and fatal outcomes. We experienced a case of bilateral cerebellar and brain stem infarction with fatal outcome resulting from vertebral artery injury associated with cervical spine trauma. A 69-year-old male was admitted to our hospital because of tetraplegia after falling down the stairs and hitting his head on the floor. Marked bony damage of the cervical spine was not apparent on radiographs and CT scans, so the injury was initially considered to be a cervical cord injury without bony damage. However, an intensity change in the intervertebral disc at C5/C6, and a ventral epidural hematoma were observed on MRI. A CT angiogram of the neck showed the right vertebral artery was completely occluded at the C4 level of the spine. Forty-eight hours after injury, the patient lapsed into drowsy consciousness. The cranial CT scan showed a massive low-density area in the bilateral cerebellar hemispheres and brain stem. Anticoagulation was initiated after a diagnosis of the right vertebral artery injury, but the patient developed bilateral cerebellar and brain stem infarction. The patient's brain herniation progressed and the patient died 52 h after injury. We considered that not only anticoagulation but also treatment for thrombosis would have been needed to prevent cranial embolism. We fully realize that early and appropriate treatment are essential to improve the treatment results, and constructing a medical system with a team of orthopedists, radiologists, and neurosurgeons is also very important. (orig.)

  5. Brain carbonic acid acidosis after acetazolamide

    DEFF Research Database (Denmark)

    Heuser, D; Astrup, J; Lassen, N A

    1975-01-01

    acidosis by I.V. injection of HCO3-minus. Acetazolamide (25 mg/kg) i.v. was followed by a marked brain acidosis which after 10 min had progressed to a drop in pH of 0.203 plus or minus 0.046 (x bar plus or minus S.D., n equals 8). The slowness ofthe development of acidosis points to a direct effect......In cats in barbiturate anesthesia extracellular pH and potassium were continously recorded from brian cortex by implanted microelectrodes. Implantation of the electrodes preserved the low permeability of the blood-brain-barrier to HCO3-minus and H+ions as indicated by the development of brain...... of the carbonic anhydrase inhibition on the brain tissue. As a further support for this conclusion was considered the finding of a prolonged response time of brain pH to HCO3-minus i.v. to CO2-minus inhalation, and to hyperventilation after the acetazolamide inhibtion. No changes in brain extracelllular potassium...

  6. Treatment of radiation syndrome with emphasis on stem cell implantation

    International Nuclear Information System (INIS)

    Ashry, O.M.

    2010-01-01

    Within few years, the possibility that the human body contains cells that can repair and regenerate damaged and diseased tissue has gone from an unlikely proposition to a virtual certainty. Patients who have received doses of radiation in the potentially low to mid-lethal range (2-6 Gy) will have depression in bone-marrow function with cessation of blood-cell production leading to pancytopenia. Selection of cases for stem cell transplantation is based upon clinical signs and symptoms. Hematopoietic stem cell which produces blood cell progeny provides support for hematopoietic and other cells within the marrow, and has also been a focus for possible tissue repair. Another cell type termed mesenchymal or stromal also exists in the marrow. This cell provides support for hematopoietic and other cells within the marrow, and has also been a focus for possible tissue repair. Stem cells are obtained from bone marrow, peripheral blood, placental and umbilical cord blood, embryonic stem cells and embryonic germ cells. These cells have great potential for clinical research due to their potential to regenerate tissue. As well known, the cryo preservation process can store any cell type, particularly blood cells, for an indeterminate time. (author)

  7. Potential feasibility of dental stem cells for regenerative therapies: stem cell transplantation and whole-tooth engineering.

    Science.gov (United States)

    Nakahara, Taka

    2011-07-01

    Multipotent mesenchymal stem cells from bone marrow are expected to be a somatic stem cell source for the development of new cell-based therapy in regenerative medicine. However, dental clinicians are unlikely to carry out autologous cell/tissue collection from patients (i.e., marrow aspiration) as a routine procedure in their clinics; hence, the utilization of bone marrow stem cells seems impractical in the dental field. Dental tissues harvested from extracted human teeth are well known to contain highly proliferative and multipotent stem cell compartments and are considered to be an alternative autologous cell source in cell-based medicine. This article provides a short overview of the ongoing studies for the potential application of dental stem cells and suggests the utilization of 2 concepts in future regenerative medicine: (1) dental stem cell-based therapy for hepatic and other systemic diseases and (2) tooth replacement therapy using the bioengineered human whole tooth, called the "test-tube dental implant." Regenerative therapies will bring new insights and benefits to the fields of clinical medicine and dentistry.

  8. Capacitive Feedthroughs for Medical Implants.

    Science.gov (United States)

    Grob, Sven; Tass, Peter A; Hauptmann, Christian

    2016-01-01

    Important technological advances in the last decades paved the road to a great success story for electrically stimulating medical implants, including cochlear implants or implants for deep brain stimulation. However, there are still many challenges in reducing side effects and improving functionality and comfort for the patient. Two of the main challenges are the wish for smaller implants on one hand, and the demand for more stimulation channels on the other hand. But these two aims lead to a conflict of interests. This paper presents a novel design for an electrical feedthrough, the so called capacitive feedthrough, which allows both reducing the size, and increasing the number of included channels. Capacitive feedthroughs combine the functionality of a coupling capacitor and an electrical feedthrough within one and the same structure. The paper also discusses the progress and the challenges of the first produced demonstrators. The concept bears a high potential in improving current feedthrough technology, and could be applied on all kinds of electrical medical implants, even if its implementation might be challenging.

  9. Stem Cell Therapy: Repurposing Cell-Based Regenerative Medicine Beyond Cell Replacement.

    Science.gov (United States)

    Napoli, Eleonora; Lippert, Trenton; Borlongan, Cesar V

    2018-02-27

    Stem cells exhibit simple and naive cellular features, yet their exact purpose for regenerative medicine continues to elude even the most elegantly designed research paradigms from developmental biology to clinical therapeutics. Based on their capacity to divide indefinitely and their dynamic differentiation into any type of tissue, the advent of transplantable stem cells has offered a potential treatment for aging-related and injury-mediated diseases. Recent laboratory evidence has demonstrated that transplanted human neural stem cells facilitate endogenous reparative mechanisms by initiating multiple regenerative processes in the brain neurogenic areas. Within these highly proliferative niches reside a myriad of potent regenerative molecules, including anti-inflammatory cytokines, proteomes, and neurotrophic factors, altogether representing a biochemical cocktail vital for restoring brain function in the aging and diseased brain. Here, we advance the concept of therapeutically repurposing stem cells not towards cell replacement per se, but rather exploiting the cells' intrinsic properties to serve as the host brain regenerative catalysts.

  10. Culture of Mouse Neural Stem Cell Precursors

    OpenAIRE

    Currle, D. Spencer; Hu, Jia Sheng; Kolski-Andreaco, Aaron; Monuki, Edwin S.

    2007-01-01

    Primary neural stem cell cultures are useful for studying the mechanisms underlying central nervous system development. Stem cell research will increase our understanding of the nervous system and may allow us to develop treatments for currently incurable brain diseases and injuries. In addition, stem cells should be used for stem cell research aimed at the detailed study of mechanisms of neural differentiation and transdifferentiation and the genetic and environmental signals that direct the...

  11. Adult neural stem cells: The promise of the future

    Directory of Open Access Journals (Sweden)

    Philippe Taupin

    2007-01-01

    Full Text Available Philippe TaupinNational Neuroscience Institute, National University of SingaporeAbstract: Stem cells are self-renewing undifferentiated cells that give rise to multiple types of specialized cells of the body. In the adult, stem cells are multipotents and contribute to homeostasis of the tissues and regeneration after injury. Until recently, it was believed that the adult brain was devoid of stem cells, hence unable to make new neurons and regenerate. With the recent evidences that neurogenesis occurs in the adult brain and neural stem cells (NSCs reside in the adult central nervous system (CNS, the adult brain has the potential to regenerate and may be amenable to repair. The function(s of NSCs in the adult CNS remains the source of intense research and debates. The promise of the future of adult NSCs is to redefine the functioning and physiopathology of the CNS, as well as to treat a broad range of CNS diseases and injuries.Keywords: neurogenesis, transdifferentiation, plasticity, cellular therapy

  12. Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation is associated with cell-type-dependent splicing of mtAspRS mRNA

    NARCIS (Netherlands)

    van Berge, Laura; Dooves, Stephanie; van Berkel, Carola G. M.; Polder, Emiel; van der Knaap, Marjo S.; Scheper, Gert C.

    2012-01-01

    LBSL (leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation) is an autosomal recessive white matter disorder with slowly progressive cerebellar ataxia, spasticity and dorsal column dysfunction. Magnetic resonance imaging shows characteristic abnormalities in the

  13. Ochratoxin A at nanomolar concentration perturbs the homeostasis of neural stem cells in highly differentiated but not in immature three-dimensional brain cell cultures.

    Science.gov (United States)

    Zurich, Marie-Gabrielle; Honegger, Paul

    2011-08-28

    Ochratoxin A (OTA), a fungal contaminant of basic food commodities, is known to be highly cytotoxic, but the pathways underlying adverse effects at subcytotoxic concentrations remain to be elucidated. Recent reports indicate that OTA affects cell cycle regulation. Therefore, 3D brain cell cultures were used to study OTA effects on mitotically active neural stem/progenitor cells, comparing highly differentiated cultures with their immature counterparts. Changes in the rate of DNA synthesis were related to early changes in the mRNA expression of neural stem/progenitor cell markers. OTA at 10nM, a concentration below the cytotoxic level, was ineffective in immature cultures, whereas in mature cultures it significantly decreased the rate of DNA synthesis together with the mRNA expression of key transcriptional regulators such as Sox2, Mash1, Hes5, and Gli1; the cell cycle activator cyclin D2; the phenotypic markers nestin, doublecortin, and PDGFRα. These effects were largely prevented by Sonic hedgehog (Shh) peptide (500ngml(-1)) administration, indicating that OTA impaired the Shh pathway and the Sox2 regulatory transcription factor critical for stem cell self-renewal. Similar adverse effects of OTA in vivo might perturb the regulation of stem cell proliferation in the adult brain and in other organs exhibiting homeostatic and/or regenerative cell proliferation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  14. Chitosan derived co-spheroids of neural stem cells and mesenchymal stem cells for neural regeneration.

    Science.gov (United States)

    Han, Hao-Wei; Hsu, Shan-Hui

    2017-10-01

    Chitosan has been considered as candidate biomaterials for neural applications. The effective treatment of neurodegeneration or injury to the central nervous system (CNS) is still in lack nowadays. Adult neural stem cells (NSCs) represents a promising cell source to treat the CNS diseases but they are limited in number. Here, we developed the core-shell spheroids of NSCs (shell) and mesenchymal stem cells (MSCs, core) by co-culturing cells on the chitosan surface. The NSCs in chitosan derived co-spheroids displayed a higher survival rate than those in NSC homo-spheroids. The direct interaction of NSCs with MSCs in the co-spheroids increased the Notch activity and differentiation tendency of NSCs. Meanwhile, the differentiation potential of MSCs in chitosan derived co-spheroids was significantly enhanced toward neural lineages. Furthermore, NSC homo-spheroids and NSC/MSC co-spheroids derived on chitosan were evaluated for their in vivo efficacy by the embryonic and adult zebrafish brain injury models. The locomotion activity of zebrafish receiving chitosan derived NSC homo-spheroids or NSC/MSC co-spheroids was partially rescued in both models. Meanwhile, the higher survival rate was observed in the group of adult zebrafish implanted with chitosan derived NSC/MSC co-spheroids as compared to NSC homo-spheroids. These evidences indicate that chitosan may provide an extracellular matrix-like environment to drive the interaction and the morphological assembly between NSCs and MSCs and promote their neural differentiation capacities, which can be used for neural regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Real Time Imaging of Biomarkers in the Parkinson's Brain Using Mini-Implantable Biosensors. II. Pharmaceutical Therapy with Bromocriptine

    Directory of Open Access Journals (Sweden)

    Patricia A. Broderick

    2009-12-01

    Full Text Available We used Neuromolecular Imaging (NMI and trademarked BRODERICK PROBE® mini-implantable biosensors, to selectively and separately detect neurotransmitters in vivo, on line, within seconds in the dorsal striatal brain of the Parkinson’s Disease (PD animal model. We directly compared our results derived from PD to the normal striatal brain of the non-Parkinson’s Disease (non-PD animal. This advanced biotechnology enabled the imaging of dopamine (DA, serotonin (5-HT, homovanillic acid (HVA a metabolite of DA, L-tryptophan (L-TP a precursor to 5-HT and peptides, dynorphin A 1-17 (Dyn A and somatostatin (somatostatin releasing inhibitory factor (SRIF. Each neurotransmitter and neurochemical was imaged at a signature electroactive oxidation/half-wave potential in dorsal striatum of the PD as compared with the non-PD animal. Both endogenous and bromocriptine-treated neurochemical profiles in PD and non-PD were imaged using the same experimental paradigm and detection sensitivities. Results showed that we have found significant neurotransmitter peptide biomarkers in the dorsal striatal brain of endogenous and bromocriptine-treated PD animals. The peptide biomarkers were not imaged in dorsal striatal brain of non-PD animals, either endogenously or bromocriptine-treated. These findings provide new pharmacotherapeutic strategies for PD patients. Thus, our findings are highly applicable to the clinical treatment of PD.

  16. Simulation of peri-implant bone healing due to immediate loading in dental implant treatments.

    Science.gov (United States)

    Chou, Hsuan-Yu; Müftü, Sinan

    2013-03-15

    The goal of this work was to investigate the role of immediate loading on the peri-implant bone healing in dental implant treatments. A mechano-regulatory tissue differentiation model that takes into account the stimuli through the solid and the fluid components of the healing tissue, and the diffusion of pluripotent stem cells into the healing callus was used. A two-dimensional axisymmetric model consisting of a dental implant, the healing callus tissue and the host bone tissue was constructed for the finite element analysis. Poroelastic material properties were assigned to the healing callus and the bone tissue. The effects of micro-motion, healing callus size, and implant thread design on the length of the bone-to-implant contact (BIC) and the bone volume (BV) formed in the healing callus were investigated. In general, the analysis predicted formation of a continuous layer of soft tissue along the faces of the implant which are parallel to the loading direction. This was predicted to be correlated with the high levels of distortional strain transferred through the solid component of the stimulus. It was also predicted that the external threads on the implant, redistribute the interfacial load, thus help reduce the high distortional stimulus and also help the cells to differentiate to bone tissue. In addition, the region underneath the implant apex was predicted to experience high fluid stimulus that results in the development of soft tissue. The relationship between the variables considered in this study and the outcome measures, BV and BIC, was found to be highly nonlinear. A three-way analysis of variance (ANOVA) of the results was conducted and it showed that micro-motion presents the largest hindrance to bone formation during healing. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Fully Implantable Deep Brain Stimulation System with Wireless Power Transmission for Long-term Use in Rodent Models of Parkinson's Disease.

    Science.gov (United States)

    Heo, Man Seung; Moon, Hyun Seok; Kim, Hee Chan; Park, Hyung Woo; Lim, Young Hoon; Paek, Sun Ha

    2015-03-01

    The purpose of this study to develop new deep-brain stimulation system for long-term use in animals, in order to develop a variety of neural prostheses. Our system has two distinguished features, which are the fully implanted system having wearable wireless power transfer and ability to change the parameter of stimulus parameter. It is useful for obtaining a variety of data from a long-term experiment. To validate our system, we performed pre-clinical test in Parkinson's disease-rat models for 4 weeks. Through the in vivo test, we observed the possibility of not only long-term implantation and stability, but also free movement of animals. We confirmed that the electrical stimulation neither caused any side effect nor damaged the electrodes. We proved possibility of our system to conduct the long-term pre-clinical test in variety of parameter, which is available for development of neural prostheses.

  18. Biological Strategies for Improved Osseointegration and Osteoinduction of Porous Metal Orthopedic Implants

    Science.gov (United States)

    Riester, Scott M.; Bonin, Carolina A.; Kremers, Hilal Maradit; Dudakovic, Amel; Kakar, Sanjeev; Cohen, Robert C.; Westendorf, Jennifer J.

    2015-01-01

    The biological interface between an orthopedic implant and the surrounding host tissue may have a dramatic effect upon clinical outcome. Desired effects include bony ingrowth (osseointegration), stimulation of osteogenesis (osteoinduction), increased vascularization, and improved mechanical stability. Implant loosening, fibrous encapsulation, corrosion, infection, and inflammation, as well as physical mismatch may have deleterious clinical effects. This is particularly true of implants used in the reconstruction of load-bearing synovial joints such as the knee, hip, and the shoulder. The surfaces of orthopedic implants have evolved from solid-smooth to roughened-coarse and most recently, to porous in an effort to create a three-dimensional architecture for bone apposition and osseointegration. Total joint surgeries are increasingly performed in younger individuals with a longer life expectancy, and therefore, the postimplantation lifespan of devices must increase commensurately. This review discusses advancements in biomaterials science and cell-based therapies that may further improve orthopedic success rates. We focus on material and biological properties of orthopedic implants fabricated from porous metal and highlight some relevant developments in stem-cell research. We posit that the ideal primary and revision orthopedic load-bearing metal implants are highly porous and may be chemically modified to induce stem cell growth and osteogenic differentiation, while minimizing inflammation and infection. We conclude that integration of new biological, chemical, and mechanical methods is likely to yield more effective strategies to control and modify the implant–bone interface and thereby improve long-term clinical outcomes. PMID:25348836

  19. Cancer Stem Cells – New Approach to Cancerogenensis and Treatment

    Directory of Open Access Journals (Sweden)

    Zuzana Mačingová

    2008-01-01

    Full Text Available Recently, there is an increasing evidence supporting the theory of cancer stem cells not only in leukemia but also in solid cancer. To date, the existence of cancer stem cells has been proven in acute and chronic myeloid leukemia, in breast cancer, in brain tumors, in lung cancer and gastrointestinal tumors. This review is focusing on the recent discovery of stem cells in leukemia, human brain tumors and breast cancer. A small population of cells in the tumor (less than 1 % shows the potential to give rise to the tumor and its growth. These cells have a substantial characteristic of stem cells – ability for self-renewal without loss of proliferation capacity with each cell division. Furthermore they are immortal, rather resistant to treatment and express typical markers of stem cells. The origin of these resident cancer stem cells is not clear. Whether the cancer stem cells originate from normal stem cells in consequence of genetic and epigenetic changes and/or redifferentiation from somatic tumor cells to the stem-like cells remains to be investigated. We propose the idea of the relation between normal tissue stem cells and cancer stem cells and their populations – progenitor cells. Based on this we highlight one of the major characteristic of stem cell – plasticity, which is equally important in the physiological regeneration process as well as carcinogenesis. Furthermore, we consider the microenvironment as a limiting factor for tumor genesis in AML, breast cancer and brain tumors. Thus the biological properties of cancer stem cells are just beginning to be revealed, the continuation of these studies should lead to the development of cancer stem cells target therapies for cancer treatment.

  20. Total Hip Intraoperative Femur Fracture: Do the Design Enhancements of a Second-Generation Tapered-Wedge Stem Reduce the Incidence?

    Science.gov (United States)

    Colacchio, Nicholas D; Robbins, Claire E; Aghazadeh, Mehran S; Talmo, Carl T; Bono, James V

    2017-10-01

    Intraoperative femur fracture (IFF) is a well-known complication in primary uncemented total hip arthroplasty (THA). Variations in implant instrumentation design and operative technique may influence the risk of IFF. This study investigates IFF between a standard uncemented tapered-wedge femoral stem and its second-generation successor with the following design changes: size-specific medial curvature, proportional incremental stem growth, modest reduction in stem length, and distal lateral relief. A single experienced surgeon's patient database was retrospectively queried for IFF occurring during primary uncemented THA using a standard tapered-wedge femoral stem system or a second-generation stem. All procedures were performed using soft tissue preserving anatomic capsule repair and posterior approach. The primary outcome measure was IFF. A z-test of proportions was performed to determine significant difference between the 2 stems with respect to IFF. Patient demographics, Dorr classification, and implant characteristics were also examined. Forty-one of 1510 patients (2.72%) who received a standard tapered-wedge femoral stem sustained an IFF, whereas 5 of 800 patients (0.63%) using the second-generation stem incurred an IFF. No other significant associations were found. A standard tapered-wedge femoral stem instrumentation system resulted in greater than 4 times higher incidence of IFF than its second-generation successor used for primary uncemented THA. Identifying risk factors for IFF is necessary to facilitate implant system improvements and thus maximize patient outcomes. Copyright © 2017. Published by Elsevier Inc.

  1. Combining 3-dimensional degradable electrostatic spinning scaffold and dental follicle cells to build peri-implant periodontium

    Directory of Open Access Journals (Sweden)

    Ximu Zhang

    2013-01-01

    Full Text Available Introduction: Some inevitable problems, such as concentrated bite force and lacked ability of self-renewal, are proved to be the major challenge in the management of implants failures. Thus, it is meaningful to find an ideal dental implant harboring its own peri-implant periodontium, just as the natural teeth. Various studies attempted to reconstruct the periodontium around implants, but unfortunately, it was previously revealed that the artificial periodotium around implants was just a wilderness of fibers, while without the physiological function of natural periodontium, like sensory and homeostatic. The Hypothesis: In this paper, we propose a hypothesis that a modified three-dimensional scaffold with reconstructed peri-implant tissues can be a network for stem cells differentiation. After seeded on the scaffold, stem cells produce various growth factors and differentiate to different orientations in places necessary. This hypothesis, if proven to be valid, will offer a novel and effective therapy for the restoration of missing teeth by implant. Evaluation of the Hypothesis: The scaffold involves three different tissues. Though degradation rate of electrospinning scaffold is under control, its degradation rate should be in consistent with the generation of three tissues. Therefore, the relative experiments are necessary to define the best rate of degradation. Further verification is necessary to check whether the rebuilt cementum, bone and periodontium are strong enough to keep the implant stable and maintain its function.

  2. Effects of sevoflurane on adenylate cyclase and phosphodiesterases activity in brain of rats

    International Nuclear Information System (INIS)

    Feng Changdong; Yang Jianping; Dai Tijun

    2009-01-01

    Objective: To investigate the effects of sevoflurane on c adenylate cyclase (AC) and phosphodiesterases (PDE) activity in the cerebrocortex, hippocampus and brain stem of rats, and to examine the role of cAMP in sevoflurane anesthesia. Methods: Fourty SD rats were delaminately designed and allocated randomly to 5 groups inhaling 1.5% sevoflurane i.e., no recovery (recovery group, n=8) and one hour after righting reflexrecovery (aware group, n=8). The brain tissues were rapidly dissected into cerebrocortex and hippocampus and brain stem.Then the adenylate cyclase and phosphodiesterases activity were assessed. Results: So far as the activity of AC is concerned, compared with the control group, the activity of AC in the cerebrocortex, hippocampus and brain stem brain stem of induction group and anesthesia group, the cerebrocortex, and hippocampus in the recovery group were significantly increased; compared with those in the anesthesia group, the activity of AC in the cerebrocortex, hippocampus and brain stem of aware group were significantly decreased (P<0.05); For the activity of PDE, compared with the control group, the activity of PDE in the cerebrocortex, hippocampus and brain stem in the induction group and anesthesia group was significantly decreased, compared with that in anesthesia group, the activity of PDE in the cerebrocortex, hippocampus and brain stem of recovery group and aware group was significantly increased (P<0.05). Conclusion: cAMP may play an important role in sevoflurane anesthesia. (authors)

  3. Hardware-related infections after deep brain stimulation surgery: review of incidence, severity and management in 212 single-center procedures in the first year after implantation.

    Science.gov (United States)

    Piacentino, Massimo; Pilleri, Manuela; Bartolomei, Luigi

    2011-12-01

    Device-related infection is a common occurrence after deep brain stimulation (DBS) surgery, and may result in additional interventions and a loss of efficacy of therapy. This retrospective review aimed to evaluate the incidence, severity and management of device-related infections in 212 DBS procedures performed in our institute. Data on 106 patients, in whom 212 DBS procedures were performed between 2001 and 2011 at our institute by a single neurosurgeon (M.P.), were reviewed to assess the incidence, severity, management and clinical characteristics of infections in the first year after the implantation of a DBS system. Infections occurred in 8.5% of patients and 4.2% of procedures. Of the nine infections, eight involved the neurostimulator and extensions, and one the whole system. The infections occurred 30.7 days after implantation: 7 within 30 days and 2 within 6 months. Infected and uninfected patients were comparable in terms of age, sex, indication for DBS implantation and neurostimulator location. In eight cases, the system components involved were removed and re-implanted after 3 months, while in one case the complete hardware was removed and not re-implanted. The overall incidence of postoperative infections after DBS system implantation was 4.2%; this rate decreased over time. All infections required further surgery. Correct and timely management of partial infections may result in successful salvage of part of the system.

  4. Addition of Adipose-Derived Stem Cells to Mesenchymal Stem Cell Sheets Improves Bone Formation at an Ectopic Site

    Directory of Open Access Journals (Sweden)

    Zhifa Wang

    2016-02-01

    Full Text Available To determine the effect of adipose-derived stem cells (ADSCs added to bone marrow-derived mesenchymal stem cell (MSC sheets on bone formation at an ectopic site. We isolated MSCs and ADSCs from the same rabbits. We then prepared MSC sheets for implantation with or without ADSCs subcutaneously in the backs of severe combined immunodeficiency (SCID mice. We assessed bone formation at eight weeks after implantation by micro-computed tomography and histological analysis. In osteogenic medium, MSCs grew to form multilayer sheets containing many calcium nodules. MSC sheets without ADSCs formed bone-like tissue; although neo-bone and cartilage-like tissues were sparse and unevenly distributed by eight weeks after implantation. In comparison, MSC sheets with ADSCs promoted better bone regeneration as evidenced by the greater density of bone, increased mineral deposition, obvious formation of blood vessels, large number of interconnected ossified trabeculae and woven bone structures, and greater bone volume/total volume within the composite constructs. Our results indicate that although sheets of only MSCs have the potential to form tissue engineered bone at an ectopic site, the addition of ADSCs can significantly increase the osteogenic potential of MSC sheets. Thus, the combination of MSC sheets with ADSCs may be regarded as a promising therapeutic strategy to stimulate bone regeneration.

  5. MRI patterns in prolonged low response states following traumatic brain injury in children and adolescents.

    Science.gov (United States)

    Patrick, Peter D; Mabry, Jennifer L; Gurka, Matthew J; Buck, Marcia L; Boatwright, Evelyn; Blackman, James A

    2007-01-01

    To explore the relationship between location and pattern of brain injury identified on MRI and prolonged low response state in children post-traumatic brain injury (TBI). This observational study compared 15 children who spontaneously recovered within 30 days post-TBI to 17 who remained in a prolonged low response state. 92.9% of children with brain stem injury were in the low response group. The predicted probability was 0.81 for brain stem injury alone, increasing to 0.95 with a regional pattern of injury to the brain stem, basal ganglia, and thalamus. Low response state in children post-TBI is strongly correlated with two distinctive regions of injury: the brain stem alone, and an injury pattern to the brain stem, basal ganglia, and thalamus. This study demonstrates the need for large-scale clinical studies using MRI as a tool for outcome assessment in children and adolescents following severe TBI.

  6. Usefullness of three-dimensional templating software to quantify the contact state between implant and femur in total hip arthroplasty.

    Science.gov (United States)

    Inoue, Daisuke; Kabata, Tamon; Maeda, Toru; Kajino, Yoshitomo; Fujita, Kenji; Hasegawa, Kazuhiro; Yamamoto, Takashi; Takagi, Tomoharu; Ohmori, Takaaki; Tsuchiya, Hiroyuki

    2015-12-01

    It would be ideal if surgeons could precisely confirm whether the planned femoral component achieves the best fit and fill of implant and femur. However, the cortico-cancellous interfaces can be difficult to standardize using plain radiography, and therefore, determining the contact state is a subjective decision by the examiner. Few reports have described the use of CT-based three-dimensional templating software to quantify the contact state of stem and femur in detail. The purpose of this study was to use three-dimensional templating software to quantify the implant-femur contact state and develop a technique to analyze the initial fixation pattern of a cementless femoral stem. We conducted a retrospective review of 55 hips in 53 patients using a short proximal fit-and-fill anatomical stem (APS Natural-Hip™ System). All femurs were examined by density mapping which can visualize and digitize the contact state. We evaluated the contact state of implant and femur by using density mapping. The varus group (cases that had changed varus 2° by 3 months after surgery) consisted of 11 hips. The varus group showed no significant difference with regard to cortical contact in the proximal medial portion (Gruen 7), but the contact area in the distal portion (Gruen 3 and Gruen 5) was significantly lower than that of non-varus group. Density mapping showed that the stem only has to be press-fit to the medial calcar, but also must fill the distal portion of the implant in order to achieve the ideal contact state. Our results indicated that quantifying the contact state of implant and femur by using density mapping is a useful technique to accurately analyze the fixation pattern of a cementless femoral stem.

  7. Road for understanding cancer stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Erzik, Can

    2007-01-01

    There is increasing evidence suggesting that stem cells are susceptive to carcinogenesis and, consequently, can be the origin of many cancers. Recently, the neoplastic potential of stem cells has been supported by many groups showing the existence of subpopulations with stem cell characteristics...... in tumor biopsies such as brain and breast. Evidence supporting the cancer stem cell hypothesis has gained impact due to progress in stem cell biology and development of new models to validate the self-renewal potential of stem cells. Recent evidence on the possible identification of cancer stem cells may...... offer an opportunity to use these cells as future therapeutic targets. Therefore, model systems in this field have become very important and useful. This review will focus on the state of knowledge on cancer stem cell research, including cell line models for cancer stem cells. The latter will, as models...

  8. Critical appraisal of cerebral blood flow measured from brain stem and cerebellar regions after 133 Xe inhalation in humans

    International Nuclear Information System (INIS)

    Juge, O.; Meyer, J.S.; Sakai, F.; Yamaguchi, F.; Yamamoto, M.; Shaw, T.

    1979-01-01

    Validity of regional blood flow (rCBF) measurements recorded over the human posterior fossa after 133Xe inhalation was tested. Recording of counts from both brain stem and cerebellum (BSC) was reproducible and contamination by counts derived from surrounding anatomical structures was low and no greater than that found over hemispheres. BSC flow values showed significant correlation with the state of awareness as judged by clinical and EEG evaluation

  9. Intramyocardial implantation of differentiated rat bone marrow mesenchymal stem cells enhanced by TGF-β1 improves cardiac function in heart failure rats

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Y. [Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, Hebei (China); Liu, B. [Department of Pathology, the First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei (China); Wang, H.P. [Department of Histology and Embryology, Hebei North University, Zhangjiakou, Hebei (China); Zhang, L. [Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, Hebei (China)

    2016-05-31

    The present study tested the hypotheses that i) transforming growth factor beta 1 (TGF-β1) enhances differentiation of rat bone marrow mesenchymal stem cells (MSCs) towards the cardiomyogenic phenotype and ii) intramyocardial implantation of the TGF-β1-treated MSCs improves cardiac function in heart failure rats. MSCs were treated with different concentrations of TGF-β1 for 72 h, and then morphological characteristics, surface antigens and mRNA expression of several transcription factors were assessed. Intramyocardial implantation of these TGF-β1-treated MSCs to infarcted heart was also investigated. MSCs were initially spindle-shaped with irregular processes. On day 28 after TGF-β1 treatment, MSCs showed fusiform shape, orientating parallel with one another, and were connected with adjoining cells forming myotube-like structures. Immunofluorescence revealed the expression of cardiomyocyte-specific proteins, α-sarcomeric actin and troponin T, in these cells. The mRNA expression of GATA4 and Nkx2.5 genes was slightly increased on day 7, enhanced on day 14 and decreased on day 28 while α-MHC gene was not expressed on day 7, but expressed slightly on day 14 and enhanced on day 28. Transmission electron microscopy showed that the induced cells had myofilaments, z line-like substances, desmosomes, and gap junctions, in contrast with control cells. Furthermore, intramyocardial implantation of TGF-β1-treated MSCs to infarcted heart reduced scar area and increased the number of muscle cells. This structure regeneration was concomitant with the improvement of cardiac function, evidenced by decreased left ventricular end-diastolic pressure, increased left ventricular systolic pressure and increased maximal positive pressure development rate. Taken together, these results indicate that intramyocardial implantation of differentiated MSCs enhanced by TGF-β1 improved cardiac function in heart failure rats.

  10. Intramyocardial implantation of differentiated rat bone marrow mesenchymal stem cells enhanced by TGF-β1 improves cardiac function in heart failure rats

    International Nuclear Information System (INIS)

    Lv, Y.; Liu, B.; Wang, H.P.; Zhang, L.

    2016-01-01

    The present study tested the hypotheses that i) transforming growth factor beta 1 (TGF-β1) enhances differentiation of rat bone marrow mesenchymal stem cells (MSCs) towards the cardiomyogenic phenotype and ii) intramyocardial implantation of the TGF-β1-treated MSCs improves cardiac function in heart failure rats. MSCs were treated with different concentrations of TGF-β1 for 72 h, and then morphological characteristics, surface antigens and mRNA expression of several transcription factors were assessed. Intramyocardial implantation of these TGF-β1-treated MSCs to infarcted heart was also investigated. MSCs were initially spindle-shaped with irregular processes. On day 28 after TGF-β1 treatment, MSCs showed fusiform shape, orientating parallel with one another, and were connected with adjoining cells forming myotube-like structures. Immunofluorescence revealed the expression of cardiomyocyte-specific proteins, α-sarcomeric actin and troponin T, in these cells. The mRNA expression of GATA4 and Nkx2.5 genes was slightly increased on day 7, enhanced on day 14 and decreased on day 28 while α-MHC gene was not expressed on day 7, but expressed slightly on day 14 and enhanced on day 28. Transmission electron microscopy showed that the induced cells had myofilaments, z line-like substances, desmosomes, and gap junctions, in contrast with control cells. Furthermore, intramyocardial implantation of TGF-β1-treated MSCs to infarcted heart reduced scar area and increased the number of muscle cells. This structure regeneration was concomitant with the improvement of cardiac function, evidenced by decreased left ventricular end-diastolic pressure, increased left ventricular systolic pressure and increased maximal positive pressure development rate. Taken together, these results indicate that intramyocardial implantation of differentiated MSCs enhanced by TGF-β1 improved cardiac function in heart failure rats

  11. Aging differentially affects male and female neural stem cell neurogenic properties

    Directory of Open Access Journals (Sweden)

    Jay Waldron

    2010-09-01

    Full Text Available Jay Waldron1, Althea McCourty1, Laurent Lecanu1,21The Research Institute of the McGill University Health Centre, Montreal, Canada; 2Department of Medicine, McGill University, Montreal, Quebec, CanadaPurpose: Neural stem cell transplantation as a brain repair strategy is a very promising technology. However, despite many attempts, the clinical success remains very deceiving. Despite clear evidence that sexual dimorphism rules many aspects of human biology, the occurrence of a sex difference in neural stem cell biology is largely understudied. Herein, we propose to determine whether gender is a dimension that drives the fate of neural stem cells through aging. Should it occur, we believe that neural stem cell sexual dimorphism and its variation during aging should be taken into account to refine clinical approaches of brain repair strategies.Methods: Neural stem cells were isolated from the subventricular zone of three- and 20-month-old male and female Long-Evans rats. Expression of the estrogen receptors, ERα and ERβ, progesterone receptor, androgen receptor, and glucocorticoid receptor was analyzed and quantified by Western blotting on undifferentiated neural stem cells. A second set of neural stem cells was treated with retinoic acid to trigger differentiation, and the expression of neuronal, astroglial, and oligodendroglial markers was determined using Western blotting.Conclusion: We provided in vitro evidence that the fate of neural stem cells is affected by sex and aging. Indeed, young male neural stem cells mainly expressed markers of neuronal and oligodendroglial fate, whereas young female neural stem cells underwent differentiation towards an astroglial phenotype. Aging resulted in a lessened capacity to express neuron and astrocyte markers. Undifferentiated neural stem cells displayed sexual dimorphism in the expression of steroid receptors, in particular ERα and ERβ, and the expression level of several steroid receptors increased

  12. Nanotubular topography enhances the bioactivity of titanium implants.

    Science.gov (United States)

    Huang, Jingyan; Zhang, Xinchun; Yan, Wangxiang; Chen, Zhipei; Shuai, Xintao; Wang, Anxun; Wang, Yan

    2017-08-01

    Surface modification on titanium implants plays an important role in promoting mesenchymal stem cell (MSC) response to enhance osseointegration persistently. In this study, nano-scale TiO 2 nanotube topography (TNT), micro-scale sand blasted-acid etched topography (SLA), and hybrid sand blasted-acid etched/nanotube topography (SLA/TNT) were fabricated on the surfaces of titanium implants. Although the initial cell adherence at 60 min among TNT, SLA and TNT/SLA was not different, SLA and SLA/TNT presented to be rougher and suppressed the proliferation of MSC. TNT showed hydrophilic surface and balanced promotion of cellular functions. After being implanted in rabbit femur models, TNT displayed the best osteogenesis inducing ability as well as strong bonding strength to the substrate. These results indicate that nano-scale TNT provides favorable surface topography for improving the clinical performance of endosseous implants compared with micro and hybrid micro/nano surfaces, suggesting a promising and reliable surface modification strategy of titanium implants for clinical application. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Early radiation changes of normal dog brain following internal and external brain irradiation: A preliminary report

    International Nuclear Information System (INIS)

    Chin, H.; Maruyama, Y.; Markesbery, W.; Goldstein, S.; Wang, P.; Tibbs, P.; Young, B.; Feola, J.; Beach, L.

    1984-01-01

    To examine radiation-induced changes in the normal brain, internal or external radiation was given to normal dog brain. Seven medium-sized dogs were used in this study. Two dogs were controls and an ice-pick (plastic implant applicator) was placed in the right frontal lobe for about 5 hours but no irradiation. Two dogs underwent Cs-137 brain implantation for 4 and 5 hours, respectively using an ice-pick technique. Two dogs were given internal neutron irradiation using the same technique of intracerebral ice-pick brachytherapy. One dog received an external photon irradiation using 6-Mev Linear Accelerator. Postmortem microscopic examination was made to study the early cerebral changes to irradiation in three dogs: one control with no irradiation; one received intracerebral Cesium implantation; and one external photon irradiation. Vascular change was the most prominent microscopic finding. There were hemorrhage, endothelial proliferation and fibrinoid changes of small vessel wall. Most of the changes were localized in the white matter and the cortex remained intact. Details (CT, NMR and histological studies) are discussed

  14. Interactions between bio-tribocorrosion phenomena and cellular response of titanium-based femoral stems

    OpenAIRE

    Runa, Maria João Carvalho

    2016-01-01

    PhD thesis in Biomedical Engineering In orthopedics, the loosening/failure of the femoral stem of hip implants is a major concern. In uncemented Ti-based implants, the tribochemical reactions occurring at the implant/bone interface due to micromotion are known to contribute to these failures. However, the bio-tribocorrosion behavior of metallic materials and related mechanisms, induced by relative movements in a biological environment, is a complex process, largely unknown at p...

  15. Electromagnetic interference of mobile phones with electronic implants

    International Nuclear Information System (INIS)

    Kainz, W.

    2000-03-01

    Chapter 1:Interference matrix: The objective of Chapter 1 was to give an overview of the implants used at present and their electromagnetic compatibility (EMC). The evaluation of the available literature provides an estimate of the probability of electronic implants being influenced by various interference sources. A literature search at the AKH (Allgemeines Krankenhaus) in Vienna and at the Technical University of Vienna in the FIZ (Fach-Informations-Zentrum) -Biomedizinische Technik, Medline, Pascal Biomed, CC Search und Embase databases yielded 236 relevant publications. At present 12 different implants are used: pacemaker, defibrillator, cochlear and brain-stem implants, neurostimulators, spinal-cord stimulators, spinal-fusion stimulators, telemetry systems, artificial hearts, drug-delivery systems, neurological pulse generators, visual prosthetics and implantable patient chips. The frequency with which they are used and the EMC on exposure to the various interference sources was summarized. Publications on EMC were found only for the first six implant types and only for 30% of the possible combinations of implant type and interference source. Based on the number of the implants examined, the probability of interference was calculated and summarized in the interference matrix. Chapter 2:Measurements on the phantom: No publication on the electromagnetic compatibility of neurological pulse generators (NPG) could be found. This implant has been used increasingly in the last few years to treat Parkinson's disease. A phantom was built to examine this implant at 900 MHz. The electromagnetic compatibility was measured by exposing the NPG to the fields of ten different 900 MHz GSM mobile phones. Every mobile phone was tested in three different positions relative to the phantom, with four electrode configurations and four stimulation parameters. No interference was found even at a maximum transmit power of 2 watts. Further tests with half-wave dipoles and increased

  16. Growth of melanoma brain tumors monitored by photoacoustic microscopy

    Science.gov (United States)

    Staley, Jacob; Grogan, Patrick; Samadi, Abbas K.; Cui, Huizhong; Cohen, Mark S.; Yang, Xinmai

    2010-07-01

    Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.

  17. Deep brain stimulation: custom-made silicone-coated pulse-generator implantation after allergic reaction to generator compounds.

    Science.gov (United States)

    Anthofer, Judith; Herbst, Andreas; Janzen, Annettte; Lange, Max; Brawanski, Alexander; Schlaier, Juergen

    2018-02-01

    Deep brain stimulation for Parkinson's disease has become an established treatment option in recent years. The method and its application in clinical practice has proved to be safe and effective. Nevertheless, procedure-related and hardware-related complications occur. We present a rare case of a patient with an allergic reaction to the impulse generator. The patient suffered from delayed wound-healing deficits with several wound revisions and generator repositionings. After diagnosis of an allergic reaction to components of the generator, a custom-made silicon-coated model was implanted. Hereafter, no wound healing-deficit occurred throughout long-term follow-up. Allergic reaction to hardware components may lead to wound-healing deficits. In such cases, custom-made silicon-coated models may be an effective treatment option.

  18. Brain receptors for thyrotropin releasing hormone in morphine tolerant-dependent rats

    Energy Technology Data Exchange (ETDEWEB)

    Bhargava, H.N.; Das, S.

    1986-03-01

    The effect of chronic treatment of rats with morphine and its subsequent withdrawal on the brain receptors for thyrotropin releasing hormone (TRH) labeled with /sup 3/H-(3MeHis/sup 2/)TRH (MeTRH). Male Sprague Dawley rats were implanted with 4 morphine pellets (each containing 75 mg morphine base) during a 3-day period. Placebo pellet implanted rats served as controls. Both tolerance to and dependence on morphine developed as a result of this procedure. For characterization of brain TRH receptors, the animals were sacrificed 72 h after the implantation of first pellet. In another set of animals the pellets were removed and were sacrificed 24 h later. The binding of /sup 3/H-MeTRH to membranes prepared from brain without the cerebellum was determined. /sup 3/H-MeTRH bound to brain membranes prepared from placebo pellet implanted rats at a single high affinity site with a B/sub max/ value of 33.50 +/- 0.97 fmol/mg protein and a K/sub d/ of 5.18 +/- 0.21 nM. Implantation of morphine pellets did not alter the B/sub max/ value of /sup 3/H-MeTRH but decreased the K/sub d/ value significantly. Abrupt or naloxone precipitated withdrawal of morphine did not alter B/sub max/ or the K/sub d/ values. The binding of /sup 3/H-MeTRH to brain areas was also determined. The results suggest that the development of tolerance to morphine is associated with enhanced sensitivity of brain TRH receptors, however abrupt withdrawal of morphine does not change the characteristics of brain TRH receptors.

  19. Embryonic Stem Cell Proteins and MicroRNAs in the Etiology of Germ Cell Cancer

    NARCIS (Netherlands)

    R. Eini (Ronak)

    2013-01-01

    textabstractIn the early 1980s, a population of unique cells was isolated from the inner cell mass (ICM) of the mouse pre-implantation embryo named embryonic stem (ES) cells. These cells were generated by removing the ICM from pre-implantation blastocysts. The resulting cells were found to be

  20. Long-term results of uncemented alumina acetabular implants.

    Science.gov (United States)

    Boehler, M; Knahr, K; Plenk, H; Walter, A; Salzer, M; Schreiber, V

    1994-01-01

    We report the clinical and tribological performance of 67 ceramic acetabular prostheses implanted between 1976 and 1979 without bone cement. They articulated with ceramic femoral heads mounted on mental femoral stems. After a mean elapsed period of 144 months, 59 sockets were radiographically stable but two showed early signs and six showed late signs of loosening. Four of the loose sockets have been revised. Histological analysis of the retrieved tissue showed a fibrous membrane around all the implants, with fibrocartilage in some. There was no bone ingrowth, and the fibrous membrane was up to 6 mm thick and infiltrated with lymphocytes, plasma cells, and macrophages. Intra- and extracellular birefringent wear particles were seen. Tribological analysis showed total wear rates in two retrieved alumina-on-alumina joints of 2.6 microns per year in a stable implant and 68 microns in a loose implant. Survival analysis showed a revision rate of 12.4% at 136 months.

  1. STEM CELL RESEARCH-CONCEPT AND CONTROVERSIES

    African Journals Online (AJOL)

    Dr. E. P. Gharoro

    cells, heart cells, brain cells, etc.). Some researchers regard them as offering the greatest potential for the .... anaemia, heart damage, corneal damage, etc. To be useful for transplant purposes, stem cells must ... activity in the brain was demonstrated contradicting caja's “no new neurons” dogma. However, research into.

  2. [The primary stability between manual and robot assisted implantation of hip prostheses: A biomechanical study on synthetic femurs].

    Science.gov (United States)

    Decking, J; Gerber, A; Kränzlein, J; Meurer, A; Böhm, B; Plitz, W

    2004-01-01

    We investigated the initial stability of cementless stems implanted with robotic milling and conventional manual broaching. Proximally porous structured stems (G2, ESKA-Implants, Luebeck, Germany) were implanted into synthetic femora. In one group, the femoral cavity was prepared by a CT-based robot (CASPAR, URS-Ortho, Germany) with a high-speed milling head. In the other group, femora were rasped manually with broaches. The broaches had 1 mm proximal press-fit, the robotic cavities 1.5 mm. The implants were exposed to 15 000 loading cycles with 1 000 +/- 500 N. The direction of forces on the implant head were chosen to simulate stair climbing. Internal rotation and translation (caudal, dorsal and lateral) of the implants were measured by linear transducers. The robotic group showed significantly less reversible motion regarding translation in caudal, dorsal and lateral directions. The standard deviations of implant motions were smaller in the robotic group. Using robotic preparation of the femur, initial stability was higher and more consistent than with manual broaching, but differences in undersizing of the cavities created in the femur in relation to the implant may have contributed to these differences for the most part. In-vitro-loading experiments focusing on femoral cavities with varying press-fits are recommended before the introduction of new implants or operating procedures.

  3. The relationship of silicone breast implants and cancer at other sites.

    Science.gov (United States)

    Brinton, Louise A

    2007-12-01

    Although most attention regarding the effects of silicone breast implants on cancer risk has focused on breast cancer, there have also been concerns regarding effects on other cancers. This includes malignancies that could occur as a result of foreign-body carcinogenesis (sarcomas) or immune alterations (hematopoietic malignancies), or cancers suggested as possibly elevated on the basis of previous epidemiologic studies (cancers of the cervix, vulva, lung, and brain). Searches of the English language literature on the topic of silicone breast implants and cancer risk were conducted and reviewed to determine relationships that might have etiologic relevance. Epidemiologic studies provide no support for an increased risk of either sarcoma or multiple myeloma among breast implant recipients, disputing clinical and laboratory findings suggesting such a link. Although a number of epidemiologic studies have demonstrated elevated risks of cervical, vulvar, and lung cancers among breast implant patients, it is likely that these excesses relate more to lifestyle characteristics (e.g., cigarette smoking, sexual behavior) than to the effects of the implants. Brain cancer excesses, suggested in one study, have not been confirmed in either an update of the mortality experience in this study or on the basis of other investigations. At present, there is no convincing evidence that breast implants alter the risk of nonbreast malignancies. Breast implant patients should continue to be monitored for longer term risks and to assess whether cancer risk is influenced by various patient and implant characteristics.

  4. Three challenges for future research on cochlear implants

    Directory of Open Access Journals (Sweden)

    David B. Pisoni

    2017-12-01

    which specific biological and neurocognitive factors are responsible for individual differences or understanding the underlying sensory and neurocognitive basis for variability in performance, it is impossible to select a specific approach to habilitation after a deaf adult or child receives a CI. Deaf adults and children who are performing poorly with their CIs are not a homogeneous group and may differ in many different ways from each other, reflecting the dysfunction of multiple brain systems associated with both congenital and acquired deafness. Hearing loss is not only an ear issue, it is also a brain issue too reflecting close links between perception and action and brain, body and world working together as a functionally integrated information processing system to support robust speech recognition and spoken language processing after implantation. Keywords: Hearing loss, Cochlear implants, Outcomes following implantation

  5. Hard tissue formation of STRO-1-selected rat dental pulp stem cells in vivo.

    NARCIS (Netherlands)

    Yang, X.; Walboomers, X.F.; Beucken, J.J.J.P van den; Bian, Z.; Fan, M.; Jansen, J.A.

    2009-01-01

    The objective of this study was to examine hard tissue formation of STRO-1-selected rat dental pulp-derived stem cells, seeded into a calcium phosphate ceramic scaffold, and implanted subcutaneously in mice. Previously, STRO-1 selection was used to obtain a mesenchymal stem cell progenitor

  6. Systemic Injection of Neural Stem/progenitor Cells in Mice With Chronic EAE

    OpenAIRE

    Donegà, Matteo; Giusto, Elena; Cossetti, Chiara; Schaeffer, Julia; Pluchino, Stefano

    2014-01-01

    Neural stem/precursor cells (NPCs) are a promising stem cell source for transplantation approaches aiming at brain repair or restoration in regenerative neurology. This directive has arisen from the extensive evidence that brain repair is achieved after focal or systemic NPC transplantation in several pre clinical models of neurological diseases.

  7. Extending the Limits of Wireless Power Transfer to Miniaturized Implantable Electronic Devices

    Directory of Open Access Journals (Sweden)

    Hugo Dinis

    2017-12-01

    Full Text Available Implantable electronic devices have been evolving at an astonishing pace, due to the development of fabrication techniques and consequent miniaturization, and a higher efficiency of sensors, actuators, processors and packaging. Implantable devices, with sensing, communication, actuation, and wireless power are of high demand, as they pave the way for new applications and therapies. Long-term and reliable powering of such devices has been a challenge since they were first introduced. This paper presents a review of representative state of the art implantable electronic devices, with wireless power capabilities, ranging from inductive coupling to ultrasounds. The different power transmission mechanisms are compared, to show that, without new methodologies, the power that can be safely transmitted to an implant is reaching its limit. Consequently, a new approach, capable of multiplying the available power inside a brain phantom for the same specific absorption rate (SAR value, is proposed. In this paper, a setup was implemented to quadruple the power available in the implant, without breaking the SAR limits. A brain phantom was used for concept verification, with both simulation and measurement data.

  8. Can Arthroplasty Stem INfluence Outcome? (CASINO): a randomized controlled equivalence trial of 125 mm versus 150 mm Exeter V40 stems in total hip arthroplasty.

    Science.gov (United States)

    Hamilton, David F; Ohly, Nicholas E; Gaston, Paul

    2018-04-16

    The use of shorter length femoral stems during total hip arthroplasty has been suggested to accommodate wider patient femoral geometry and offer maximal bone preservation. However, cemented short-stem designs may increase the risk of varus stem malalignment and influence patient outcomes. CASINO is a multi-centre randomised equivalence trial that will recruit 220 patients undergoing total hip arthroplasty for osteoarthritis at two NHS hospitals in Scotland. Patients will be aged 45-80, undergoing unilateral primary hip arthroplasty, with no plan for contralateral procedure within the study timeframe, and able to comply with the protocol. Participants will be randomised to receive either a short (125 mm) or a standard (150 mm) Exeter V40 stem. The Contemporary acetabular component will be used in all cases. All implants will be cemented. Patient pain, function and satisfaction will be assessed using change from baseline measurement in Oxford Hip Score, Forgotten Joint Score, EQ-5D, pain numerical rating scores, and patient satisfaction questionnaire at baseline and at 1 and 2 years following surgery. Radiographic assessment will evaluate stem position and will be appraised by independent reviewers. Patients will be blind to implant allocation. Stem length may be associated with outcome; however, we can find no randomised trial in which researchers investigated the effect of stem length on patient outcome following cemented total hip arthroplasty. The aim of this trial is to determine if the use of short cemented stems offers equivalent patient outcomes to those achieved following surgery with standard length stems. International Standard Randomised Controlled Trial Number, ISRCTN13154542 , Registered on 30 June 2017.

  9. Comparative study of expression and activity of glucose transporters between stem cell-derived brain microvascular endothelial cells and hCMEC/D3 cells.

    Science.gov (United States)

    Al-Ahmad, Abraham J

    2017-10-01

    Glucose constitutes a major source of energy of mammalian brains. Glucose uptake at the blood-brain barrier (BBB) occurs through a facilitated glucose transport, through glucose transporter 1 (GLUT1), although other isoforms have been described at the BBB. Mutations in GLUT1 are associated with the GLUT1 deficiency syndrome, yet none of the current in vitro models of the human BBB maybe suited for modeling such a disorder. In this study, we investigated the expression of glucose transporters and glucose diffusion across brain microvascular endothelial cells (BMECs) derived from healthy patient-derived induced pluripotent stem cells (iPSCs). We investigated the expression of different glucose transporters at the BBB using immunocytochemistry and flow cytometry and measured glucose uptake and diffusion across BMEC monolayers obtained from two iPSC lines and from hCMEC/D3 cells. BMEC monolayers showed expression of several glucose transporters, in particular GLUT1, GLUT3, and GLUT4. Diffusion of glucose across the monolayers was mediated via a saturable transcellular mechanism and partially inhibited by pharmacological inhibitors. Taken together, our study suggests the presence of several glucose transporters isoforms at the human BBB and demonstrates the feasibility of modeling glucose across the BBB using patient-derived stem cells. Copyright © 2017 the American Physiological Society.

  10. Cortical Plasticity after Cochlear Implantation

    DEFF Research Database (Denmark)

    Petersen, Bjørn; Gjedde, Albert; Wallentin, Mikkel

    2013-01-01

    recently implanted adult implant recipients listened to running speech or speech-like noise in four sequential PET sessions at each milestone. CI listeners with postlingual hearing loss showed differential activation of left superior temporal gyrus during speech and speech-like stimuli, unlike CI listeners...... with prelingual hearing loss. Furthermore, Broca's area was activated as an effect of time, but only in CI listeners with postlingual hearing loss. The study demonstrates that adaptation to the cochlear implant is highly related to the history of hearing loss. Speech processing in patients whose hearing loss...... occurred after the acquisition of language involves brain areas associated with speech comprehension, which is not the case for patients whose hearing loss occurred before the acquisition of language. Finally, the findings confirm the key role of Broca's area in restoration of speech perception, but only...

  11. Stem Cell Therapy for Erectile Dysfunction.

    Science.gov (United States)

    Matz, Ethan L; Terlecki, Ryan; Zhang, Yuanyuan; Jackson, John; Atala, Anthony

    2018-04-06

    The prevalence of erectile dysfunction (ED) is substantial and continues to rise. Current therapeutics for ED consist of oral medications, intracavernosal injections, vacuum erection devices, and penile implants. While such options may manage the disease state, none of these modalities, however, restore function. Stem cell therapy has been evaluated for erectile restoration in animal models. These cells have been derived from multiple tissues, have varied potential, and may function via local engraftment or paracrine signaling. Bone marrow-derived stem cells (BMSC) and adipose-derived stem cells (ASC) have both been used in these models with noteworthy effects. Herein, we will review the pathophysiology of ED, animal models, current and novel stem-cell based therapeutics, clinical trials and areas for future research. The relevant literature and contemporary data using keywords, "stem cells and erectile dysfunction" was reviewed. Examination of evidence supporting the association between erectile dysfunction and adipose derived stem cells, bone marrow derived stem cells, placental stem cells, urine stem cells and stem cell therapy respectively. Placental-derived stem cells and urine-derived stem cells possess many similar properties as BMSC and ASC, but the methods of acquisition are favorable. Human clinical trials have already demonstrated successful use of stem cells for improvement of erectile function. The future of stem cell research is constantly being evaluated, although, the evidence suggests a place for stem cells in erectile dysfunction therapeutics. Matz EL, Terlecki R, Zhang Y, et al. Stem Cell Therapy for Erectile Dysfunction. Sex Med Rev 2018;XX:XXX-XXX. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

  12. Reestablishing speech understanding through musical ear training after cochlear implantation: a study of the potential cortical plasticity in the brain

    DEFF Research Database (Denmark)

    Petersen, Bjørn; Mortensen, Malene V; Gjedde, Albert

    2009-01-01

    the behavioral and neurologic effects of musical ear training on CI users' speech and music perception. The goal is to find and work out musical methods to improve CI users' auditory capabilities and, in a longer perspective, provide an efficient strategy for improving speech understanding for both adults......Cochlear implants (CIs) provide impressive speech perception for persons with severe hearing loss, but many CI recipients fail in perceiving speech prosody and music. Successful rehabilitation depends on cortical plasticity in the brain and postoperative measures. The present study evaluates...

  13. Five-Year Safety Data for More than 55,000 Subjects following Breast Implantation: Comparison of Rare Adverse Event Rates with Silicone Implants versus National Norms and Saline Implants.

    Science.gov (United States)

    Singh, Navin; Picha, George J; Hardas, Bhushan; Schumacher, Andrew; Murphy, Diane K

    2017-10-01

    The U.S. Food and Drug Administration has required postapproval studies of silicone breast implants to evaluate the incidence of rare adverse events over 10 years after implantation. The Breast Implant Follow-Up Study is a large 10-year study (>1000 U.S. sites) evaluating long-term safety following primary augmentation, revision-augmentation, primary reconstruction, or revision-reconstruction with Natrelle round silicone breast implants compared with national norms and outcomes with saline implants. Targeted adverse events in subjects followed for 5 to 8 years included connective tissue diseases, neurologic diseases, cancer, and suicide. The safety population comprised 55,279 women (primary augmentation, n = 42,873; revision-augmentation, n = 6837; primary reconstruction, n = 4828; and revision-reconstruction, n = 741). No targeted adverse events occurred at significantly greater rates in silicone implant groups versus national norms across all indications. The standardized incidence rate (observed/national norm) for all indications combined was 1.4 for cervical/vulvar cancer, 0.8 for brain cancer, 0.3 for multiple sclerosis, and 0.1 for lupus/lupus-like syndrome. Silicone implants did not significantly increase the risk for any targeted adverse events compared with saline implants. The risk of death was similar with silicone versus saline implants across all indications. The suicide rate (10.6 events per 100,000 person-years) was not significantly higher than the national norm. No implant-related deaths occurred. Results from 5 to 8 years of follow-up for a large number of subjects confirmed the safety of Natrelle round silicone implants, with no increased risk of systemic disease or suicide versus national norms or saline implants. Therapeutic, II.

  14. Heterogeneity of brain blood flow and permeability during acute hypertension

    International Nuclear Information System (INIS)

    Baumbach, G.L.; Heistad, D.D.

    1985-01-01

    The purpose of this study was to examine regional autoregulation of blood flow in the brain during acute hypertension. In anesthetized cats severe hypertension increased blood flow more in cerebrum (159%) and cerebellum (106%) than brain stem (58%). In contrast to the heterogeneous autoregulatory response, hypocapnia produced uniform vasoconstriction in the brain. The authors also compared vasodilatation during severe hypertension with vasodilatation during hypercapnia. During hypercapnia, blood flow increased as much in brain stem, as in cerebrum and cerebellum. Thus, regional differences in autoregulation appear to be specific for autoregulatory stimulus and are not secondary to nonspecific differences in vasoconstrictor or vasodilator capacity. To determine whether the blood-brain barrier is more susceptible to hypertensive disruption in regions with less effective autoregulation, permeability of the barrier was quantitated with 125 I-albumin. Severe hypertension produced disruption of the barrier in cerebrum but not in brain stem. Thus, there are parallel differences in effectiveness of autoregulation and susceptibility to disruption of the blood-brain barrier in different regions of the brain

  15. Fabrication of a Biologically-Implantable, Multiplexed, Multielectrode Array of JFETS for Cortical Implantation.

    Science.gov (United States)

    1984-12-01

    which could be implanted at the surface of the brain. Electrodes of microfine dimensions I-1 . ..6...to check the operation of the diffusion furnace oxidation tube by comparing measured thicknesses of the oxide against calculated values. Oxide Growth...faster rate than that of Eq ), (11-2). Initial adjustments made prior to using the diffusion furnace included: (1) profiling the oxidation tube to

  16. Induction of pluripotent stem cells from fibroblast cultures.

    Science.gov (United States)

    Takahashi, Kazutoshi; Okita, Keisuke; Nakagawa, Masato; Yamanaka, Shinya

    2007-01-01

    Clinical application of embryonic stem (ES) cells faces difficulties regarding use of embryos, as well as tissue rejection after implantation. One way to circumvent these issues is to generate pluripotent stem cells directly from somatic cells. Somatic cells can be reprogrammed to an embryonic-like state by the injection of a nucleus into an enucleated oocyte or by fusion with ES cells. However, little is known about the mechanisms underlying these processes. We have recently shown that the combination of four transcription factors can generate ES-like pluripotent stem cells directly from mouse fibroblast cultures. The cells, named induced pluripotent stem (iPS) cells, can be differentiated into three germ layers and committed to chimeric mice. Here we describe detailed methods and tips for the generation of iPS cells.

  17. HMGA1 silencing reduces stemness and temozolomide resistance in glioblastoma stem cells.

    Science.gov (United States)

    Colamaio, Marianna; Tosti, Nadia; Puca, Francesca; Mari, Alessia; Gattordo, Rosaria; Kuzay, Yalçın; Federico, Antonella; Pepe, Anna; Sarnataro, Daniela; Ragozzino, Elvira; Raia, Maddalena; Hirata, Hidenari; Gemei, Marica; Mimori, Koshi; Del Vecchio, Luigi; Battista, Sabrina; Fusco, Alfredo

    2016-10-01

    Glioblastoma multiforme (GBM) develops from a small subpopulation of stem-like cells, which are endowed with the ability to self-renew, proliferate and give rise to progeny of multiple neuroepithelial lineages. These cells are resistant to conventional chemo- and radiotherapy and are hence also responsible for tumor recurrence. HMGA1 overexpression has been shown to correlate with proliferation, invasion, and angiogenesis of GBMs and to affect self-renewal of cancer stem cells from colon cancer. The role of HMGA1 in GBM tumor stem cells is not completely understood. We have investigated the role of HMGA1 in brain tumor stem cell (BTSC) self-renewal, stemness and resistance to temozolomide by shRNA- mediated HMGA1 silencing. We first report that HMGA1 is overexpressed in a subset of BTSC lines from human GBMs. Then, we show that HMGA1 knockdown reduces self-renewal, sphere forming efficiency and stemness, and sensitizes BTSCs to temozolomide. Interestingly, HMGA1 silencing also leads to reduced tumor initiation ability in vivo. These results demonstrate a pivotal role of HMGA1 in cancer stem cell gliomagenesis and endorse HMGA1 as a suitable target for CSC-specific GBM therapy.

  18. In vivo differentiation of induced pluripotent stem cells into neural stem cells by chimera formation.

    Science.gov (United States)

    Choi, Hyun Woo; Hong, Yean Ju; Kim, Jong Soo; Song, Hyuk; Cho, Ssang Gu; Bae, Hojae; Kim, Changsung; Byun, Sung June; Do, Jeong Tae

    2017-01-01

    Like embryonic stem cells, induced pluripotent stem cells (iPSCs) can differentiate into all three germ layers in an in vitro system. Here, we developed a new technology for obtaining neural stem cells (NSCs) from iPSCs through chimera formation, in an in vivo environment. iPSCs contributed to the neural lineage in the chimera, which could be efficiently purified and directly cultured as NSCs in vitro. The iPSC-derived, in vivo-differentiated NSCs expressed NSC markers, and their gene-expression pattern more closely resembled that of fetal brain-derived NSCs than in vitro-differentiated NSCs. This system could be applied for differentiating pluripotent stem cells into specialized cell types whose differentiation protocols are not well established.

  19. Stem cell transplantation therapy for multifaceted therapeutic benefits after stroke.

    Science.gov (United States)

    Wei, Ling; Wei, Zheng Z; Jiang, Michael Qize; Mohamad, Osama; Yu, Shan Ping

    2017-10-01

    One of the exciting advances in modern medicine and life science is cell-based neurovascular regeneration of damaged brain tissues and repair of neuronal structures. The progress in stem cell biology and creation of adult induced pluripotent stem (iPS) cells has significantly improved basic and pre-clinical research in disease mechanisms and generated enthusiasm for potential applications in the treatment of central nervous system (CNS) diseases including stroke. Endogenous neural stem cells and cultured stem cells are capable of self-renewal and give rise to virtually all types of cells essential for the makeup of neuronal structures. Meanwhile, stem cells and neural progenitor cells are well-known for their potential for trophic support after transplantation into the ischemic brain. Thus, stem cell-based therapies provide an attractive future for protecting and repairing damaged brain tissues after injury and in various disease states. Moreover, basic research on naïve and differentiated stem cells including iPS cells has markedly improved our understanding of cellular and molecular mechanisms of neurological disorders, and provides a platform for the discovery of novel drug targets. The latest advances indicate that combinatorial approaches using cell based therapy with additional treatments such as protective reagents, preconditioning strategies and rehabilitation therapy can significantly improve therapeutic benefits. In this review, we will discuss the characteristics of cell therapy in different ischemic models and the application of stem cells and progenitor cells as regenerative medicine for the treatment of stroke. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Brain death and related issues

    International Nuclear Information System (INIS)

    Akhtar, M.; Mushtaq, S.; Jamil, K.; Ahmed, S.

    2003-01-01

    Concerns about the erroneous diagnosis of death and premature burial have been expressed from times immemorial. Patients with brain stem death have absolutely no chance of recovery. Brain death is considered at par with death in most of the countries. General public in most parts of the world shows reluctance to accept this concept due to different social, cultural and religious backgrounds and state of literacy and awareness. The criteria for the diagnosis of brain death have been established which include certain pre-conditions, exclusions and tests of the brain stem function. These criteria are universally accepted. The criteria in children are somewhat different from the adults. The subject is intimately related with organ transplantation. If the patients is registered as organ donor or the family consents, organs can be harvested from brain dead patients for transplantation. Pakistan is amongst the few countries where no legislation exists to accept brain death as being at par with death of an individual, and to facilitate and regulate, cadaveric organ donation and transplantation. (author)

  1. YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Han, Dasol; Byun, Sung-Hyun; Park, Soojeong; Kim, Juwan; Kim, Inhee; Ha, Soobong; Kwon, Mookwang; Yoon, Keejung, E-mail: keejung@skku.edu

    2015-02-27

    Mammalian brain development is regulated by multiple signaling pathways controlling cell proliferation, migration and differentiation. Here we show that YAP/TAZ enhance embryonic neural stem cell characteristics in a cell autonomous fashion using diverse experimental approaches. Introduction of retroviral vectors expressing YAP or TAZ into the mouse embryonic brain induced cell localization in the ventricular zone (VZ), which is the embryonic neural stem cell niche. This change in cell distribution in the cortical layer is due to the increased stemness of infected cells; YAP-expressing cells were colabeled with Sox2, a neural stem cell marker, and YAP/TAZ increased the frequency and size of neurospheres, indicating enhanced self-renewal- and proliferative ability of neural stem cells. These effects appear to be TEA domain family transcription factor (Tead)–dependent; a Tead binding-defective YAP mutant lost the ability to promote neural stem cell characteristics. Consistently, in utero gene transfer of a constitutively active form of Tead2 (Tead2-VP16) recapitulated all the features of YAP/TAZ overexpression, and dominant negative Tead2-EnR resulted in marked cell exit from the VZ toward outer cortical layers. Taken together, these results indicate that the Tead-dependent YAP/TAZ signaling pathway plays important roles in neural stem cell maintenance by enhancing stemness of neural stem cells during mammalian brain development. - Highlights: • Roles of YAP and Tead in vivo during mammalian brain development are clarified. • Expression of YAP promotes embryonic neural stem cell characteristics in vivo in a cell autonomous fashion. • Enhancement of neural stem cell characteristics by YAP depends on Tead. • Transcriptionally active form of Tead alone can recapitulate the effects of YAP. • Transcriptionally repressive form of Tead severely reduces stem cell characteristics.

  2. YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner

    International Nuclear Information System (INIS)

    Han, Dasol; Byun, Sung-Hyun; Park, Soojeong; Kim, Juwan; Kim, Inhee; Ha, Soobong; Kwon, Mookwang; Yoon, Keejung

    2015-01-01

    Mammalian brain development is regulated by multiple signaling pathways controlling cell proliferation, migration and differentiation. Here we show that YAP/TAZ enhance embryonic neural stem cell characteristics in a cell autonomous fashion using diverse experimental approaches. Introduction of retroviral vectors expressing YAP or TAZ into the mouse embryonic brain induced cell localization in the ventricular zone (VZ), which is the embryonic neural stem cell niche. This change in cell distribution in the cortical layer is due to the increased stemness of infected cells; YAP-expressing cells were colabeled with Sox2, a neural stem cell marker, and YAP/TAZ increased the frequency and size of neurospheres, indicating enhanced self-renewal- and proliferative ability of neural stem cells. These effects appear to be TEA domain family transcription factor (Tead)–dependent; a Tead binding-defective YAP mutant lost the ability to promote neural stem cell characteristics. Consistently, in utero gene transfer of a constitutively active form of Tead2 (Tead2-VP16) recapitulated all the features of YAP/TAZ overexpression, and dominant negative Tead2-EnR resulted in marked cell exit from the VZ toward outer cortical layers. Taken together, these results indicate that the Tead-dependent YAP/TAZ signaling pathway plays important roles in neural stem cell maintenance by enhancing stemness of neural stem cells during mammalian brain development. - Highlights: • Roles of YAP and Tead in vivo during mammalian brain development are clarified. • Expression of YAP promotes embryonic neural stem cell characteristics in vivo in a cell autonomous fashion. • Enhancement of neural stem cell characteristics by YAP depends on Tead. • Transcriptionally active form of Tead alone can recapitulate the effects of YAP. • Transcriptionally repressive form of Tead severely reduces stem cell characteristics

  3. Interspecies chimera between primate embryonic stem cells and mouse embryos: monkey ESCs engraft into mouse embryos, but not post-implantation fetuses.

    Science.gov (United States)

    Simerly, Calvin; McFarland, Dave; Castro, Carlos; Lin, Chih-Cheng; Redinger, Carrie; Jacoby, Ethan; Mich-Basso, Jocelyn; Orwig, Kyle; Mills, Parker; Ahrens, Eric; Navara, Chris; Schatten, Gerald

    2011-07-01

    Unequivocal evidence for pluripotency in which embryonic stem cells contribute to chimeric offspring has yet to be demonstrated in human or nonhuman primates (NHPs). Here, rhesus and baboons ESCs were investigated in interspecific mouse chimera generated by aggregation or blastocyst injection. Aggregation chimera produced mouse blastocysts with GFP-nhpESCs at the inner cell mass (ICM), and embryo transfers (ETs) generated dimly-fluorescencing abnormal fetuses. Direct injection of GFP-nhpESCs into blastocysts produced normal non-GFP-fluorescencing fetuses. Injected chimera showed >70% loss of GFP-nhpESCs after 21 h culture. Outgrowths of all chimeric blastocysts established distinct but separate mouse- and NHP-ESC colonies. Extensive endogenous autofluorescence compromised anti-GFP detection and PCR analysis did not detect nhpESCs in fetuses. NhpESCs localize to the ICM in chimera and generate pregnancies. Because primate ESCs do not engraft post-implantation, and also because endogenous autofluorescence results in misleading positive signals, interspecific chimera assays for pluripotency with primate stem cells is unreliable with the currently available ESCs. Testing primate ESCs reprogrammed into even more naïve states in these inter-specific chimera assays will be an important future endeavor. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Implantable optogenetic device with CMOS IC technology for simultaneous optical measurement and stimulation

    Science.gov (United States)

    Haruta, Makito; Kamiyama, Naoya; Nakajima, Shun; Motoyama, Mayumi; Kawahara, Mamiko; Ohta, Yasumi; Yamasaki, Atsushi; Takehara, Hiroaki; Noda, Toshihiko; Sasagawa, Kiyotaka; Ishikawa, Yasuyuki; Tokuda, Takashi; Hashimoto, Hitoshi; Ohta, Jun

    2017-05-01

    In this study, we have developed an implantable optogenetic device that can measure and stimulate neurons by an optical method based on CMOS IC technology. The device consist of a blue LED array for optically patterned stimulation, a CMOS image sensor for acquiring brain surface image, and eight green LEDs surrounding the CMOS image sensor for illumination. The blue LED array is placed on the CMOS image sensor. We implanted the device in the brain of a genetically modified mouse and successfully demonstrated the stimulation of neurons optically and simultaneously acquire intrinsic optical images of the brain surface using the image sensor. The integrated device can be used for simultaneously measuring and controlling neuronal activities in a living animal, which is important for the artificial control of brain functions.

  5. Migration and strains induced by different designs of force-closed stems for THA.

    Science.gov (United States)

    Griza, Sandro; Gomes, Luiz Sérgio Marcelino; Cervieri, André; Strohaecker, Telmo Roberto

    2015-01-01

    Subtle differences in stem design can result in different mechanical responses of the total hip arthroplasty. Tests measuring migration of the stem relative to the femur, as well as the strains in the cement mantle and on the femur can detect different mechanical behavior between stems. In this article, conical, double and triple tapered stems were implanted in composite femurs and subjected to static and cyclic loads. Stems differed mainly on taper angle, calcar radius and proximal stiffness. Stem migration and strains on the femur and in the cement mantle were achieved. Significant differences (p mechanical tests were able to detect significant differences in the behavior of these resembling stems. Stem proximal stiffness and the calcar radius of the stem influence its rotational stability and the strain transmission to the femur.

  6. Effectiveness of mesenchymal stems cells cultured by hanging drop vs. conventional culturing on the repair of hypoxic-ischemic-damaged mouse brains, measured by stemness gene expression

    Directory of Open Access Journals (Sweden)

    Lou Yongli

    2016-01-01

    Full Text Available In this study, we investigated the therapeutic effects of Human Mesenchymal Stem Cells (hMSCs cultured by hanging drop and conventional culturing methods on cerebellar repair in hypoxic-ischemic (HI brain injured mice. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR was used to analyze the expression levels of three stemness genes, Oct4, Sox2 and Nanog, and the migration related gene CXCR4. MSC prepared by hanging drop or conventional techniques were administered intranasally to nine day old mice, and analyzed by MRI at day 28. Results indicate that the MSCs, especially the hanging drop cultured MSCs, significantly improved the mice’s cerebellar damage repair. MSCs derived from the hanging drop culture were smaller than those from the conventional culture. The gene expression levels were significantly increased for the MSCs derived from the hanging drop culture. The mechanism might relate to the fact that the hanging drop cultured MSCs can be kept in an undifferentiated state, resulting in its higher expression level of migration receptor of CXCR4.

  7. Placenta-an alternative source of stem cells

    International Nuclear Information System (INIS)

    Matikainen, Tiina; Laine, Jarmo

    2005-01-01

    The two most promising practical applications of human stem cells are cellular replacement therapies in human disease and toxicological screening of candidate drug molecules. Both require a source of human stem cells that can be isolated, purified, expanded in number and differentiated into the cell type of choice in a controlled manner. Currently, uses of both embryonic and adult stem cells are investigated. While embryonic stem cells are pluripotent and can differentiate into any specialised cell type, their use requires establishment of embryonic stem cell lines using the inner cell mass of an early pre-implantation embryo. As the blastocyst is destroyed during the process, ethical issues need to be carefully considered. The use of embryonic stem cells is also limited by the difficulties in growing large numbers of the cells without inducing spontaneous differentiation, and the problems in controlling directed differentiation of the cells. The use of adult stem cells, typically derived from bone marrow, but also from other tissues, is ethically non-controversial but their differentiation potential is more limited than that of the embryonic stem cells. Since human cord blood, umbilical cord, placenta and amnion are normally discarded at birth, they provide an easily accessible alternative source of stem cells. We review the potential and current status of the use of adult stem cells derived from the placenta or umbilical cord in therapeutic and toxicological applications

  8. Augmented cartilage regeneration by implantation of cellular versus acellular implants after bone marrow stimulation: a systematic review and meta-analysis of animal studies

    Directory of Open Access Journals (Sweden)

    Michiel W. Pot

    2017-10-01

    Full Text Available Bone marrow stimulation may be applied to regenerate focal cartilage defects, but generally results in transient clinical improvement and formation of fibrocartilage rather than hyaline cartilage. Tissue engineering and regenerative medicine strive to develop new solutions to regenerate hyaline cartilage tissue. This systematic review and meta-analysis provides a comprehensive overview of current literature and assesses the efficacy of articular cartilage regeneration by implantation of cell-laden versus cell-free biomaterials in the knee and ankle joint in animals after bone marrow stimulation. PubMed and EMBASE (via OvidSP were systematically searched using tissue engineering, cartilage and animals search strategies. Included were primary studies in which cellular and acellular biomaterials were implanted after applying bone marrow stimulation in the knee or ankle joint in healthy animals. Study characteristics were tabulated and outcome data were collected for meta-analysis for studies applying semi-quantitative histology as outcome measure (117 studies. Cartilage regeneration was expressed on an absolute 0–100% scale and random effects meta-analyses were performed. Implantation of cellular biomaterials significantly improved cartilage regeneration by 18.6% compared to acellular biomaterials. No significant differences were found between biomaterials loaded with stem cells and those loaded with somatic cells. Culture conditions of cells did not affect cartilage regeneration. Cartilage formation was reduced with adipose-derived stem cells compared to other cell types, but still improved compared to acellular scaffolds. Assessment of the risk of bias was impaired due to incomplete reporting for most studies. Implantation of cellular biomaterials improves cartilage regeneration compared to acellular biomaterials.

  9. Augmented cartilage regeneration by implantation of cellular versus acellular implants after bone marrow stimulation: a systematic review and meta-analysis of animal studies.

    Science.gov (United States)

    Pot, Michiel W; van Kuppevelt, Toin H; Gonzales, Veronica K; Buma, Pieter; IntHout, Joanna; de Vries, Rob B M; Daamen, Willeke F

    2017-01-01

    Bone marrow stimulation may be applied to regenerate focal cartilage defects, but generally results in transient clinical improvement and formation of fibrocartilage rather than hyaline cartilage. Tissue engineering and regenerative medicine strive to develop new solutions to regenerate hyaline cartilage tissue. This systematic review and meta-analysis provides a comprehensive overview of current literature and assesses the efficacy of articular cartilage regeneration by implantation of cell-laden versus cell-free biomaterials in the knee and ankle joint in animals after bone marrow stimulation. PubMed and EMBASE (via OvidSP) were systematically searched using tissue engineering, cartilage and animals search strategies. Included were primary studies in which cellular and acellular biomaterials were implanted after applying bone marrow stimulation in the knee or ankle joint in healthy animals. Study characteristics were tabulated and outcome data were collected for meta-analysis for studies applying semi-quantitative histology as outcome measure (117 studies). Cartilage regeneration was expressed on an absolute 0-100% scale and random effects meta-analyses were performed. Implantation of cellular biomaterials significantly improved cartilage regeneration by 18.6% compared to acellular biomaterials. No significant differences were found between biomaterials loaded with stem cells and those loaded with somatic cells. Culture conditions of cells did not affect cartilage regeneration. Cartilage formation was reduced with adipose-derived stem cells compared to other cell types, but still improved compared to acellular scaffolds. Assessment of the risk of bias was impaired due to incomplete reporting for most studies. Implantation of cellular biomaterials improves cartilage regeneration compared to acellular biomaterials.

  10. The effect of radial head implant shape on radiocapitellar kinematics during in vitro forearm rotation.

    Science.gov (United States)

    Shannon, Hannah L; Deluce, Simon R; Giles, Joshua W; Johnson, James A; King, Graham J W

    2015-02-01

    A number of radial head implants are in clinical use for the management of radial head fractures and their sequelae. However, the optimal shape of a radial head implant to ensure proper tracking relative to the capitellum has not been established. This in vitro biomechanical study compared radiocapitellar joint kinematics for 3 radial head implant designs as well as the native head. Eight cadaveric upper extremities were tested using a forearm rotation simulator with the elbow at 90° of flexion. Motion of the radius relative to the capitellum was optically tracked. A stem was navigated into a predetermined location and cemented in place. Three unipolar implant shapes were tested: axisymmetric, reverse-engineered patient-specific, and population-based quasi-anatomic. The patient-specific and quasi-anatomic implants were derived from measurements performed on computed tomography models. Medial-lateral and anterior-posterior translation of the radial head with respect to the capitellum varied with forearm rotation and radial head condition. A significant difference in medial-lateral (P = .03) and anterior-posterior (P = .03) translation was found between the native radial head and the 3 implants. No differences were observed among the radial head conditions except for a difference in medial-lateral translation between the axisymmetric and patient-specific implants (P = .04). Radiocapitellar kinematics of the tested radial head implants were similar in all but one comparison, and all had different kinematics from the native radial head. Patient-specific radial head implants did not prove advantageous relative to conventional implant designs. The shape of the fixed stem unipolar radial head implants had little influence on radiocapitellar kinematics when optimally positioned in this testing model. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  11. The adult brain tissue response to hollow fiber membranes of varying surface architecture with or without cotransplanted cells

    Science.gov (United States)

    Zhang, Ning

    A variety of biomaterials have been chronically implanted into the central nervous system (CNS) for repair or therapeutic purposes. Regardless of the application, chronic implantation of materials into the CNS induces injury and elicits a wound healing response, eventually leading to the formation of a dense extracellular matrix (ECM)-rich scar tissue that is associated with the segregation of implanted materials from the surrounding normal tissue. Often this reaction results in impaired performance of indwelling CNS devices. In order to enhance the performance of biomaterial-based implantable devices in the CNS, this thesis investigated whether adult brain tissue response to implanted biomaterials could be manipulated by changing biomaterial surface properties or further by utilizing the biology of co-transplanted cells. Specifically, the adult rat brain tissue response to chronically implanted poly(acrylonitrile-vinylchloride) (PAN-PVC) hollow fiber membranes (HFMs) of varying surface architecture were examined temporally at 2, 4, and 12 weeks postimplantation. Significant differences were discovered in the brain tissue response to the PAN-PVC HFMs of varying surface architecture at 4 and 12 weeks. To extend this work, whether the soluble factors derived from a co-transplanted cellular component further affect the brain tissue response to an implanted HFM in a significant way was critically exploited. The cells used were astrocytes, whose ability to influence scar formation process following CNS injury by physical contact with the host tissue had been documented in the literature. Data indicated for the first time that astrocyte-derived soluble factors ameliorate the adult brain tissue reactivity toward HFM implants in an age-dependent manner. While immature astrocytes secreted soluble factors that suppressed the brain tissue reactivity around the implants, mature astrocytes secreted factors that enhanced the gliotic response. These findings prove the feasibility

  12. Flexible deep brain neural probes based on a parylene tube structure

    Science.gov (United States)

    Zhao, Zhiguo; Kim, Eric; Luo, Hao; Zhang, Jinsheng; Xu, Yong

    2018-01-01

    Most microfabricated neural probes have limited shank length, which prevents them from reaching many deep brain structures. This paper reports deep brain neural probes with ultra-long penetrating shanks based on a simple but novel parylene tube structure. The mechanical strength of the parylene tube shank is temporarily enhanced during implantation by inserting a metal wire. The metal wire can be removed after implantation, making the implanted probe very flexible and thus minimizing the stress caused by micromotions of brain tissues. Optogenetic stimulation and chemical delivery capabilities can be potentially integrated by taking advantage of the tube structure. Single-shank prototypes with a shank length of 18.2 mm have been developed. The microfabrication process comprises of deep reactive ion etching (DRIE) of silicon, parylene conformal coating/refilling, and XeF2 isotropic silicon etching. In addition to bench-top insertion characterization, the functionality of developed probes has been preliminarily demonstrated by implanting into the amygdala of a rat and recording neural signals.

  13. Nestin-positive mesenchymal stem cells favour the astroglial lineage in neural progenitors and stem cells by releasing active BMP4

    Directory of Open Access Journals (Sweden)

    Leprince Pierre

    2004-09-01

    Full Text Available Abstract Background Spontaneous repair is limited after CNS injury or degeneration because neurogenesis and axonal regrowth rarely occur in the adult brain. As a result, cell transplantation has raised much interest as potential treatment for patients with CNS lesions. Several types of cells have been considered as candidates for such cell transplantation and replacement therapies. Foetal brain tissue has already been shown to have significant effects in patients with Parkinson's disease. Clinical use of the foetal brain tissue is, however, limited by ethical and technical problems as it requires high numbers of grafted foetal cells and immunosuppression. Alternatively, several reports suggested that mesenchymal stem cells, isolated from adult bone marrow, are multipotent cells and could be used in autograft approach for replacement therapies. Results In this study, we addressed the question of the possible influence of mesenchymal stem cells on neural stem cell fate. We have previously reported that adult rat mesenchymal stem cells are able to express nestin in defined culture conditions (in the absence of serum and after 25 cell population doublings and we report here that nestin-positive (but not nestin-negative mesenchymal stem cells are able to favour the astroglial lineage in neural progenitors and stem cells cultivated from embryonic striatum. The increase of the number of GFAP-positive cells is associated with a significant decrease of the number of Tuj1- and O4-positive cells. Using quantitative RT-PCR, we demonstrate that mesenchymal stem cells express LIF, CNTF, BMP2 and BMP4 mRNAs, four cytokines known to play a role in astroglial fate decision. In this model, BMP4 is responsible for the astroglial stimulation and oligodendroglial inhibition, as 1 this cytokine is present in a biologically-active form only in nestin-positive mesenchymal stem cells conditioned medium and 2 anti-BMP4 antibodies inhibit the nestin-positive mesenchymal

  14. Characteristics of MR imaging of brain stem glioma for the treatment of combination chemotherapy with interferon-. beta. and ACNU in addition to radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Wakabayashi, Toshihiko; Yoshida, Jun; Sugita, Kenichiro (Nagoya Univ. (Japan). Faculty of Medicine)

    1990-08-01

    In an attempt to improve the prognosis of brain stem glioma patients, a new treatment using a combination of chemotherapy of interferon-{beta}, ACNU, (1) - (4 - Amino - 2 - methyl - 5 - primidinyl) - methyl - 3 - (2-chloroethyl) - 3 -nitrosourea hydrochloride, and radiation, so called IAR therapy, was utilized on 19 patients who were diagnosed through CT and/or MRI findings as having pontine glioma. Eight of these patients were given IAR therapy at four week intervals and the changes were checked on MRI. The MRI response was classified into 3 types, that is, type 1: diffuse low intensity lesion on T{sub 1} WI changing to isodensity and tumor mass disappearing rapidly; type 2: located high intensity lesion in low intensity on T{sub 1} WI once appearing on decreasing the whole tumor size, then this lesion disappearing gradually; type 3: spotted low and/or iso mosaic intensity lesion appearing on and after treatment, with little change in tumor mass. The type 1 patients showed rapid improvement of neurological deficits and good recovery was obtained. Type 2 patients also recovered well but at recurrent periods tended to show disseminated sings intraspinally. The type 3 patients did not recover from neurological deficits well. But there were no significant differences of prognosis among these 3 types. Furthermore, MRI showed more precise data than CT scan on brain stem lesions and seemed to be more useful for diagnosis and follow-up treatment than CT scan. Though it is suggested that IAR combination therapy should be respected as the first choice for the treatment of brain stem glioma, it is strongly requested that some maintenance therapy is established for continuing the reduction time after induction of complete or partial remission with IAR therapy. (author).

  15. Fracture of a HTR-PMI cranioplastic implant after severe TBI.

    Science.gov (United States)

    López González, Antonio; Pérez Borredá, Pedro; Conde Sardón, Rebeca

    2015-02-01

    A 13-year-old girl with a large left fronto-parietal hard-tissue replacement patient-matched implant (HTR®-PMI) cranioplasty-since she suffered from a traumatic brain injury (TBI) 6 years ago-had a new severe TBI that detached and fractured the implant as well as caused a left subdural hematoma and a large frontal contusion. The hematoma and contusion were removed and the implant was substituted by a provisional titanium mesh. To the best of our knowledge, this is the first case reported about an HTR®-PMI fracture. It is theorized that the bone ingrowth into the macroporous implants, like those of hydroxyapatite, gives strength and resistance to the implant. But in the case we describe, no macroscopic bone ingrowth was detected 6 years after implantation and the traumatic force that impacted over the cranioplasty exceeded its properties.

  16. Stem cells: Concepts and prospects

    Indian Academy of Sciences (India)

    development exemplified by murine experiments motivated the ... from specific regions of the brain, cardiac stem cells from atrial ..... have also been shown to integrate and differentiate .... to vascular network structures in three dimensional.

  17. Stem Cells in Regenerative Medicine

    OpenAIRE

    Sykova, Eva; Forostyak, Serhiy

    2013-01-01

    Background: A number of cardiovascular, neurological, musculoskeletal and other diseases have a limited capacity for repair and only a modest progress has been made in treatment of brain diseases. The discovery of stem cells has opened new possibilities for the treatment of these maladies, and cell therapy now stands at the cutting-edge of modern regenerative medicine and tissue engineering. Experimental data and the first clinical trials employing stem cells have shown their broad therapeuti...

  18. Determination of trace elements in kidneys, livers and brains of rats with sealer implants by ICP-MS

    International Nuclear Information System (INIS)

    Simsek, Neslihan; Akinci, Levent; Alan, Hilal; Gecör, Orhan; Özan, Ülkü

    2017-01-01

    Following root canal treatment, sealers may contact periapical tissue. The purpose of this study was to evaluate the systemic toxic effects of epoxy resin-based sealers (AH Plus and Obtuseal). Inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure levels of trace elements (beryllium, magnesium, aluminium, calcium, chromium, arsenic and lead) in the brain, kidney and liver of rats. Twenty sterilized polyethylene tubes were then filled with AH Plus and Obtuseal and implanted into the dorsal subcutaneous tissue of 10 rats; three unoperated animals were used as a control group. After 45 days, the rats were sacrificed by cervical dislocation following anaesthesia, and brains, kidneys and livers were removed from all experimental animals. ICP-MS analysis was used to determine levels of trace elements. Data were analysed using Kruskal– Wallis and Connover post hoc tests. No significant differences were found in aluminium and calcium levels, but brains, kidneys and livers showed significantly higher amounts of magnesium and chromium than the corresponding controls. In the kidney and liver samples, arsenic levels were found to be higher than in the control group. Lead was detected at higher levels only in liver samples from the AH Plus group. Beryllium was not detected in any organ. It was concluded that AH Plus and Obtuseal release minimal quantities of trace elements when in contact with subcutaneous tissue, and further studies are needed to understand the systemic effects of these materials

  19. Mesenchymal Stem Cells of Dental Origin-Their Potential for Antiinflammatory and Regenerative Actions in Brain and Gut Damage.

    Science.gov (United States)

    Földes, Anna; Kádár, Kristóf; Kerémi, Beáta; Zsembery, Ákos; Gyires, Klára; S Zádori, Zoltán; Varga, Gábor

    2016-01-01

    Alzheimer's disease, Parkinson's disease, traumatic brain and spinal cord injury and neuroinflammatory multiple sclerosis are diverse disorders of the central nervous system. However, they are all characterized by various levels of inappropriate inflammatory/immune response along with tissue destruction. In the gastrointestinal system, inflammatory bowel disease (IBD) is also a consequence of tissue destruction resulting from an uncontrolled inflammation. Interestingly, there are many similarities in the immunopathomechanisms of these CNS disorders and the various forms of IBD. Since it is very hard or impossible to cure them by conventional manner, novel therapeutic approaches such as the use of mesenchymal stem cells, are needed. Mesenchymal stem cells have already been isolated from various tissues including the dental pulp and periodontal ligament. Such cells possess transdifferentiating capabilities for different tissue specific cells to serve as new building blocks for regeneration. But more importantly, they are also potent immunomodulators inhibiting proinflammatory processes and stimulating anti-inflammatory mechanisms. The present review was prepared to compare the immunopathomechanisms of the above mentioned neurodegenerative, neurotraumatic and neuroinflammatory diseases with IBD. Additionally, we considered the potential use of mesenchymal stem cells, especially those from dental origin to treat such disorders. We conceive that such efforts will yield considerable advance in treatment options for central and peripheral disorders related to inflammatory degeneration.

  20. Mesenchymal Stem Cell Based Therapy for Prostate Cancer

    Science.gov (United States)

    2015-11-01

    Montero-Menei, C.; Menei, P. Mesenchymal Stem Cells as Cellular Vehicles for Delivery of Nanoparticles to Brain Tumors. Biomaterials 2010, 31, 8393... Stem Cells : Considerations for Regenerative Medicine Approaches. Tissue Eng. Part B. Rev. 2010, 16, 159–168. 55. Ellem, S. J.; Taylor, R. a.; Furic, L...Award Number: W81XWH-13-1-0304 TITLE: Mesenchymal Stem Cell -Based Therapy for Prostate Cancer PRINCIPAL INVESTIGATOR: John Isaacs CONTRACTING

  1. The effect of electromagnetic radiation on the rat brain: an experimental study.

    Science.gov (United States)

    Eser, Olcay; Songur, Ahmet; Aktas, Cevat; Karavelioglu, Ergun; Caglar, Veli; Aylak, Firdevs; Ozguner, Fehmi; Kanter, Mehmet

    2013-01-01

    The aim of this study is to determine the structural changes of electromagnetic waves in the frontal cortex, brain stem and cerebellum. 24 Wistar Albino adult male rats were randomly divided into four groups: group I consisted of control rats, and groups II-IV comprised electromagnetically irradiated (EMR) with 900, 1800 and 2450 MHz. The heads of the rats were exposed to 900, 1800 and 2450 MHz microwaves irradiation for 1h per day for 2 months. While the histopathological changes in the frontal cortex and brain stem were normal in the control group, there were severe degenerative changes, shrunken cytoplasm and extensively dark pyknotic nuclei in the EMR groups. Biochemical analysis demonstrated that the Total Antioxidative Capacity level was significantly decreased in the EMR groups and also Total Oxidative Capacity and Oxidative Stress Index levels were significantly increased in the frontal cortex, brain stem and cerebellum. IL-1β level was significantly increased in the EMR groups in the brain stem. EMR causes to structural changes in the frontal cortex, brain stem and cerebellum and impair the oxidative stress and inflammatory cytokine system. This deterioration can cause to disease including loss of these areas function and cancer development.

  2. Improved corrosion resistance on biodegradable magnesium by zinc and aluminum ion implantation

    Science.gov (United States)

    Xu, Ruizhen; Yang, Xiongbo; Suen, Kai Wong; Wu, Guosong; Li, Penghui; Chu, Paul K.

    2012-12-01

    Magnesium and its alloys have promising applications as biodegradable materials, and plasma ion implantation can enhance the corrosion resistance by modifying the surface composition. In this study, suitable amounts of zinc and aluminum are plasma-implanted into pure magnesium. The surface composition, phases, and chemical states are determined, and electrochemical tests and electrochemical impedance spectroscopy (EIS) are conducted to investigate the surface corrosion behavior and elucidate the mechanism. The corrosion resistance enhancement after ion implantation is believed to stem from the more compact oxide film composed of magnesium oxide and aluminum oxide as well as the appearance of the β-Mg17Al12 phase.

  3. Three-dimensional simulated microgravity culture improves the proliferation and odontogenic differentiation of dental pulp stem cell in PLGA scaffolds implanted in mice.

    Science.gov (United States)

    Li, Yanping; He, Lina; Pan, Shuang; Zhang, Lin; Zhang, Weiwei; Yi, Hong; Niu, Yumei

    2017-02-01

    Tooth regeneration through stem cell-based therapy is a promising treatment for tooth decay and loss. Human dental pulp stem cells (hDPSCs) have been widely identified as the stem cells with the most potential for tooth tissue regeneration. However, the culture of hDPSCs in vitro for tissue engineering is challenging, as cells may proliferate slowly or/and differentiate poorly in vivo. Dynamic three‑dimensional (3D) simulated microgravity (SMG) created using the rotary cell culture system is considered to an effective tool, which contributes to several cell functions. Thus, the present study aimed to investigate the effect of dynamic 3D SMG culture on the proliferation and odontogenic differentiation abilities of hDPSCs in poly (lactic‑co‑glycolic acid) (PLGA) scaffolds in nude mice. The hDPSCs on PLGA scaffolds were maintained separately in the 3D SMG culture system and static 3D cultures with osteogenic medium for 7 days in vitro. Subsequently, the cell‑PLGA complexes were implanted subcutaneously on the backs of nude mice for 4 weeks. The results of histological and immunohistochemical examinations of Ki‑67, type I collagen, dentin sialoprotein and DMP‑1 indicated that the proliferation and odontogenic differentiation abilities of the hDPSCs prepared in the 3D SMG culture system were higher, compared with those prepared in the static culture system. These findings suggested that dynamic 3D SMG culture likely contributes to tissue engineering by improving the proliferation and odontogenic differentiation abilities of hDPSCs in vivo.

  4. Flexible, Penetrating Brain Probes Enabled by Advances in Polymer Microfabrication

    Directory of Open Access Journals (Sweden)

    Ahuva Weltman

    2016-10-01

    Full Text Available The acquisition of high-fidelity, long-term neural recordings in vivo is critically important to advance neuroscience and brain–machine interfaces. For decades, rigid materials such as metal microwires and micromachined silicon shanks were used as invasive electrophysiological interfaces to neurons, providing either single or multiple electrode recording sites. Extensive research has revealed that such rigid interfaces suffer from gradual recording quality degradation, in part stemming from tissue damage and the ensuing immune response arising from mechanical mismatch between the probe and brain. The development of “soft” neural probes constructed from polymer shanks has been enabled by advancements in microfabrication; this alternative has the potential to mitigate mismatch-related side effects and thus improve the quality of recordings. This review examines soft neural probe materials and their associated microfabrication techniques, the resulting soft neural probes, and their implementation including custom implantation and electrical packaging strategies. The use of soft materials necessitates careful consideration of surgical placement, often requiring the use of additional surgical shuttles or biodegradable coatings that impart temporary stiffness. Investigation of surgical implantation mechanics and histological evidence to support the use of soft probes will be presented. The review concludes with a critical discussion of the remaining technical challenges and future outlook.

  5. Biomimetic Composite-Metal Hip Resurfacing Implant

    Directory of Open Access Journals (Sweden)

    Habiba Bougherara

    2008-01-01

    Full Text Available Hip resurfacing technique is a conservative arthroplasty used in the young patient in which the femoral head is reshaped to accept metal cap with small guide stem. In the present investigation, a hybrid composite-metal resurfacing implant is proposed. The cup is made of carbon fiber/polyamide 12 (CF/PA12 covered with a thin layer of cobalt chrome (Co-Cr. Finite element (FE method was applied to analyze and compare the biomechanical performances of the hybrid hip resurfacing (HHR and the conventional Birmingham (BHR. Results of the finite element analysis showed that the composite implant leads to an increase in stresses in the cancellous bone by more than 15% than BHR, indicating a lower potential for stress shielding and bone fracture and higher potential for bone apposition with the HHR.

  6. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

    Directory of Open Access Journals (Sweden)

    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II

  7. Bioactive Coatings for Orthopaedic Implants—Recent Trends in Development of Implant Coatings

    Directory of Open Access Journals (Sweden)

    Bill G. X. Zhang

    2014-07-01

    Full Text Available Joint replacement is a major orthopaedic procedure used to treat joint osteoarthritis. Aseptic loosening and infection are the two most significant causes of prosthetic implant failure. The ideal implant should be able to promote osteointegration, deter bacterial adhesion and minimize prosthetic infection. Recent developments in material science and cell biology have seen the development of new orthopaedic implant coatings to address these issues. Coatings consisting of bioceramics, extracellular matrix proteins, biological peptides or growth factors impart bioactivity and biocompatibility to the metallic surface of conventional orthopaedic prosthesis that promote bone ingrowth and differentiation of stem cells into osteoblasts leading to enhanced osteointegration of the implant. Furthermore, coatings such as silver, nitric oxide, antibiotics, antiseptics and antimicrobial peptides with anti-microbial properties have also been developed, which show promise in reducing bacterial adhesion and prosthetic infections. This review summarizes some of the recent developments in coatings for orthopaedic implants.

  8. Atomic layer deposited TiO2 for implantable brain-chip interfacing devices

    International Nuclear Information System (INIS)

    Cianci, E.; Lattanzio, S.; Seguini, G.; Vassanelli, S.; Fanciulli, M.

    2012-01-01

    In this paper we investigated atomic layer deposition (ALD) TiO 2 thin films deposited on implantable neuro-chips based on electrolyte-oxide-semiconductor (EOS) junctions, implementing both efficient capacitive neuron-silicon coupling and biocompatibility for long-term implantable functionality. The ALD process was performed at 295 °C using titanium tetraisopropoxide and ozone as precursors on needle-shaped silicon substrates. Engineering of the capacitance of the EOS junctions introducing a thin Al 2 O 3 buffer layer between TiO 2 and silicon resulted in a further increase of the specific capacitance. Biocompatibility for long-term implantable neuroprosthetic systems was checked upon in-vitro treatment.

  9. MRI-induced heating of deep brain stimulation leads

    International Nuclear Information System (INIS)

    Mohsin, Syed A; Sheikh, Noor M; Saeed, Usman

    2008-01-01

    The radiofrequency (RF) field used in magnetic resonance imaging is scattered by medical implants. The scattered field of a deep brain stimulation lead can be very intense near the electrodes stimulating the brain. The effect is more pronounced if the lead behaves as a resonant antenna. In this paper, we examine the resonant length effect. We also use the finite element method to compute the near field for (i) the lead immersed in inhomogeneous tissue (fat, muscle, and brain tissues) and (ii) the lead connected to an implantable pulse generator. Electric field, specific absorption rate and induced temperature rise distributions have been obtained in the brain tissue surrounding the electrodes. The worst-case scenario has been evaluated by neglecting the effect of blood perfusion. The computed values are in good agreement with in vitro measurements made in the laboratory.

  10. Teratoma Formation by Human Embryonic Stem Cells is site-dependent and enhanced by the presence of Matrigel

    DEFF Research Database (Denmark)

    Prokhorova, Tatyana A; Harkness, Linda M; Frandsen, Ulrik

    2008-01-01

    When implanted into immunodeficient mice, human embryonic stem cells (hESC) give rise to teratoma, tumour-like formations containing tissues belonging to all three germ layers. The ability to form teratoma is a sine qua non characteristic of pluripotent stem cells. However, limited data...

  11. Recovery function of the human brain stem auditory-evoked potential.

    Science.gov (United States)

    Kevanishvili, Z; Lagidze, Z

    1979-01-01

    Amplitude reduction and peak latency prolongation were observed in the human brain stem auditory-evoked potential (BEP) with preceding (conditioning) stimulation. At a conditioning interval (CI) of 5 ms the alteration of BEP was greater than at a CI of 10 ms. At a CI of 10 ms the amplitudes of some BEP components (e.g. waves I and II) were more decreased than those of others (e.g. wave V), while the peak latency prolongation did not show any obvious component selectivity. At a CI of 5 ms, the extent of the amplitude decrement of individual BEP components differed less, while the increase in the peak latencies of the later components was greater than that of the earlier components. The alterations of the parameters of the test BEPs at both CIs are ascribed to the desynchronization of intrinsic neural events. The differential amplitude reduction at a CI of 10 ms is explained by the different durations of neural firings determining various effects of desynchronization upon the amplitudes of individual BEP components. The decrease in the extent of the component selectivity and the preferential increase in the peak latencies of the later BEP components observed at a CI of 5 ms are explained by the intensification of the mechanism of the relative refractory period.

  12. miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Costello Joseph F

    2008-06-01

    Full Text Available Abstract Background Glioblastoma multiforme (GBM is an invariably fatal central nervous system tumor despite treatment with surgery, radiation, and chemotherapy. Further insights into the molecular and cellular mechanisms that drive GBM formation are required to improve patient outcome. MicroRNAs are emerging as important regulators of cellular differentiation and proliferation, and have been implicated in the etiology of a variety of cancers, yet the role of microRNAs in GBM remains poorly understood. In this study, we investigated the role of microRNAs in regulating the differentiation and proliferation of neural stem cells and glioblastoma-multiforme tumor cells. Methods We used quantitative RT-PCR to assess microRNA expression in high-grade astrocytomas and adult mouse neural stem cells. To assess the function of candidate microRNAs in high-grade astrocytomas, we transfected miR mimics to cultured-mouse neural stem cells, -mouse oligodendroglioma-derived stem cells, -human glioblastoma multiforme-derived stem cells and -glioblastoma multiforme cell lines. Cellular differentiation was assessed by immunostaining, and cellular proliferation was determined using fluorescence-activated cell sorting. Results Our studies revealed that expression levels of microRNA-124 and microRNA-137 were significantly decreased in anaplastic astrocytomas (World Health Organization grade III and glioblastoma multiforme (World Health Organization grade IV relative to non-neoplastic brain tissue (P erbB tumors and cluster of differentiation 133+ human glioblastoma multiforme-derived stem cells (SF6969. Transfection of microRNA-124 or microRNA-137 also induced G1 cell cycle arrest in U251 and SF6969 glioblastoma multiforme cells, which was associated with decreased expression of cyclin-dependent kinase 6 and phosphorylated retinoblastoma (pSer 807/811 proteins. Conclusion microRNA-124 and microRNA-137 induce differentiation of adult mouse neural stem cells, mouse

  13. Stem cells engineering for cell-based therapy.

    Science.gov (United States)

    Taupin, Philippe

    2007-09-01

    Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.

  14. Implanted hair follicle stem cells form Schwann cells that support repair of severed peripheral nerves

    OpenAIRE

    Amoh, Yasuyuki; Li, Lingna; Campillo, Raul; Kawahara, Katsumasa; Katsuoka, Kensei; Penman, Sheldon; Hoffman, Robert M.

    2005-01-01

    The hair follicle bulge area is an abundant, easily accessible source of actively growing, pluripotent adult stem cells. Nestin, a protein marker for neural stem cells, also is expressed in follicle stem cells and their immediate, differentiated progeny. The fluorescent protein GFP, whose expression is driven by the nestin regulatory element in transgenic mice, served to mark the follicle cell fate. The pluripotent nestin-driven GFP stem cells are positive for the stem cell marker CD34 but ne...

  15. Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats

    OpenAIRE

    Matveyenko, Aleksey V.; Georgia, Senta; Bhushan, Anil; Butler, Peter C.

    2010-01-01

    Embryonic stem cell therapy has been proposed as a therapeutic strategy to restore β-cell mass and function in T1DM. Recently, a group from Novocell (now ViaCyte) reported successful development of glucose-responsive islet-like structures after implantation of pancreatic endoderm (PE) derived from human embryonic stem cells (hESC) into immune-deficient mice. Our objective was to determine whether implantation of hESC-derived pancreatic endoderm from Novocell into athymic nude rats results in ...

  16. Improvement of renal function after human umbilical cord mesenchymal stem cell treatment on chronic renal failure and thoracic spinal cord entrapment: a case report.

    Science.gov (United States)

    Rahyussalim, Ahmad Jabir; Saleh, Ifran; Kurniawati, Tri; Lutfi, Andi Praja Wira Yudha

    2017-11-30

    Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Thoracic spinal cord entrapment induced by a metabolic yield deposit in patients with renal failure results in intrusion of nervous tissue and consequently loss of motor and sensory function. Human umbilical cord mesenchymal stem cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Over the past decade, advances in the field of regenerative medicine allowed development of cell therapies suitable for kidney repair. Mesenchymal stem cell studies in animal models of chronic renal failure have uncovered a unique potential of these cells for improving function and regenerating the damaged kidney. We report a case of a 62-year-old ethnic Indonesian woman previously diagnosed as having thoracic spinal cord entrapment with paraplegic condition and chronic renal failure on hemodialysis. She had diabetes mellitus that affected her kidneys and had chronic renal failure for 2 years, with creatinine level of 11 mg/dl, and no urinating since then. She was treated with human umbilical cord mesenchymal stem cell implantation protocol. This protocol consists of implantation of 16 million human umbilical cord mesenchymal stem cells intrathecally and 16 million human umbilical cord mesenchymal stem cells intravenously. Three weeks after first intrathecal and intravenous implantation she could move her toes and her kidney improved. Her creatinine level decreased to 9 mg/dl. Now after 8 months she can raise her legs and her creatinine level is 2 mg/dl with normal urinating. Human umbilical cord mesenchymal stem cell implantations led to significant improvement for spinal cord entrapment and kidney failure. The major histocompatibility in allogeneic implantation is an important issue to be addressed in the future.

  17. Utilizing two-photon fluorescence and second harmonic generation microscopy to study human bone marrow mesenchymal stem cell morphogenesis in chitosan scaffold

    Science.gov (United States)

    Su, Ping-Jung; Huang, Chi-Hsiu; Huang, Yi-You; Lee, Hsuan-Sue; Dong, Chen-Yuan

    2008-02-01

    A major goal of tissue engineering is to cultivate the cartilage in vitro. One approach is to implant the human bone marrow mesenchymal stem cells into the three dimensional biocompatible and biodegradable material. Through the action of the chondrogenic factor TGF-β3, the stem cells can be induced to secrete collagen. In this study, mesenchymal stem cells are implanted on the chitosan scaffold and TGF-β3 was added to produce the cartilage tissue and TP autofluorescence and SHG microscopy was used to image the process of chondrogenesis. With additional development, multiphoton microscopy can be developed into an effective tool for evaluating the quality of tissue engineering products.

  18. Metallic gold treatment reduces proliferation of inflammatory cells, increases expression of VEGF and FGF, and stimulates cell proliferation in the subventricular zone following experimental traumatic brain injury

    DEFF Research Database (Denmark)

    Pedersen, Mie Østergaard; Larsen, Agnete; Pedersen, Dan Sonne

    2009-01-01

    Traumatic brain injury represents a leading cause of morbidity in young individuals and there is an imperative need for neuroprotective treatments limiting the neurologic impairment following such injury. It has recently been demonstrated that bio-liberated gold ions liberated from small metallic...... gold implants reduce inflammation and neuronal apoptosis, while generating an increased neuronal stem cell response following focal brain damage. In this study mice were subjected to a unilateral traumatic cryo-lesion with concomitant injection of 25-45 microm gold particles near the lesion. Placebo...... increase in cell proliferation in both the ipsilateral and the contralateral subventricular zone was found in response to gold-treatment. In conclusion: we confirmed the previously demonstrated anti-inflammatory effect of bio-liberated gold ions, and further show that metallic gold increases growth factor...

  19. Comparison of Patient-Reported Outcome from Neck-Preserving, Short-Stem Arthroplasty and Resurfacing Arthroplasty in Younger Osteoarthritis Patients

    Directory of Open Access Journals (Sweden)

    Marius Dettmer

    2015-01-01

    Full Text Available Hip resurfacing has been considered a good treatment option for younger, active osteoarthritis patients. However, there are several identified issues concerning risk for neck fractures and issues related to current metal-on-metal implant designs. Neck-preserving short-stem implants have been discussed as a potential alternative, but it is yet unclear which method is better suited for younger adults. We compared hip disability and osteoarthritis outcome scores (HOOS from a young group of patients (n=52, age 48.9 ± 6.1 years who had received hip resurfacing (HR with a cohort of patients (n=73, age 48.2 ± 6.6 years who had received neck-preserving, short-stem implant total hip arthroplasty (THA. Additionally, durations for both types of surgery were compared. HOOS improved significantly preoperatively to last followup (>1 year in both groups (p<0.0001, η2=0.69; there were no group effects or interactions. Surgery duration was significantly longer for resurfacing (104.4 min ± 17.8 than MiniHip surgery (62.5 min ± 14.8, U=85.0, p<0.0001, η2=0.56. The neck-preserving short-stem approach may be preferable to resurfacing due to the less challenging surgery, similar outcome, and controversy regarding resurfacing implant designs.

  20. Human dental pulp stem cells and gingival fibroblasts seeded into silk fibroin scaffolds have the same ability in attracting vessels

    Directory of Open Access Journals (Sweden)

    Anna eWoloszyk

    2016-04-01

    Full Text Available Neovascularization is one of the most important processes during tissue repair and regeneration. Current healing approaches based on the use of biomaterials combined with stem cells in critical-size bone defects fail due to the insufficient implant vascularization and integration into the host tissues. Therefore, here we studied the attraction, ingrowth, and distribution of blood vessels from the chicken embryo chorioallantoic membrane into implanted silk fibroin scaffolds seeded with either human dental pulp stem cells or human gingival fibroblasts. Perfusion capacity was evaluated by non-invasive in vivo Magnetic Resonance Imaging while the number and density of blood vessels were measured by histomorphometry. Our results demonstrate that human dental pulp stem cells and gingival fibroblasts possess equal abilities in attracting vessels within silk fibroin scaffolds. Additionally, the prolonged in vitro pre-incubation period of these two cell populations favors the homogeneous distribution of vessels within silk fibroin scaffolds, which further improves implant survival and guarantees successful healing and regeneration.

  1. Combined use of transcranial magnetic stimulation and metal electrode implants: a theoretical assessment of safety considerations

    Science.gov (United States)

    Golestanirad, Laleh; Rouhani, Hossein; Elahi, Behzad; Shahim, Kamal; Chen, Robert; Mosig, Juan R.; Pollo, Claudio; Graham, Simon J.

    2012-12-01

    This paper provides a theoretical assessment of the safety considerations encountered in the simultaneous use of transcranial magnetic stimulation (TMS) and neurological interventions involving implanted metallic electrodes, such as electrocorticography. Metal implants are subject to magnetic forces due to fast alternating magnetic fields produced by the TMS coil. The question of whether the mechanical movement of the implants leads to irreversible damage of brain tissue is addressed by an electromagnetic simulation which quantifies the magnitude of imposed magnetic forces. The assessment is followed by a careful mechanical analysis determining the maximum tolerable force which does not cause irreversible tissue damage. Results of this investigation provide useful information on the range of TMS stimulator output powers which can be safely used in patients having metallic implants. It is shown that conventional TMS applications can be considered safe when applied on patients with typical electrode implants as the induced stress in the brain tissue remains well below the limit of tissue damage.

  2. Human olfactory bulb neural stem cells mitigate movement disorders in a rat model of Parkinson's disease.

    Science.gov (United States)

    Marei, Hany E S; Lashen, Samah; Farag, Amany; Althani, Asmaa; Afifi, Nahla; A, Abd-Elmaksoud; Rezk, Shaymaa; Pallini, Roberto; Casalbore, Patrizia; Cenciarelli, Carlo

    2015-07-01

    Parkinson's disease (PD) is a neurological disorder characterized by the loss of midbrain dopaminergic (DA) neurons. Neural stem cells (NSCs) are multipotent stem cells that are capable of differentiating into different neuronal and glial elements. The production of DA neurons from NSCs could potentially alleviate behavioral deficits in Parkinsonian patients; timely intervention with NSCs might provide a therapeutic strategy for PD. We have isolated and generated highly enriched cultures of neural stem/progenitor cells from the human olfactory bulb (OB). If NSCs can be obtained from OB, it would alleviate ethical concerns associated with the use of embryonic tissue, and provide an easily accessible cell source that would preclude the need for invasive brain surgery. Following isolation and culture, olfactory bulb neural stem cells (OBNSCs) were genetically engineered to express hNGF and GFP. The hNFG-GFP-OBNSCs were transplanted into the striatum of 6-hydroxydopamin (6-OHDA) Parkinsonian rats. The grafted cells survived in the lesion environment for more than eight weeks after implantation with no tumor formation. The grafted cells differentiated in vivo into oligodendrocyte-like (25 ± 2.88%), neuron-like (52.63 ± 4.16%), and astrocyte -like (22.36 ± 1.56%) lineages, which we differentiated based on morphological and immunohistochemical criteria. Transplanted rats exhibited a significant partial correction in stepping and placing in non-pharmacological behavioral tests, pole and rotarod tests. Taken together, our data encourage further investigations of the possible use of OBNSCs as a promising cell-based therapeutic strategy for Parkinson's disease. © 2014 Wiley Periodicals, Inc.

  3. Fetal guinea pig brain 15-hydroxyprostaglandin dehydrogenase: Ontogeny and effect of ethanol

    International Nuclear Information System (INIS)

    Treissman, D.; Brien, J.F.

    1991-01-01

    The objectives of this study were to determine the ontogeny of 15-hydroxyprostaglandin dehydrogenase (15-OH-PGDH) activity in the brain of the fetal guinea pig and to test the hypothesis that acute in vitro ethanol exposure produces concentration-dependent inhibition of fetal brain 15-OH-PGDH activity. Enzyme activity was determined in vitro by measuring the rate of oxidation of PGE2 to 15-keto-PGE2 using an optimized radiometric procedure. The study was conducted utilizing the whole brain of the fetal guinea pig at mean gestational ages of 34, 43 and 62 days (term, about 66 days) and the brain stem (pons and medulla) of the fetal guinea pig at mean gestational ages of 43 and 62 days. The direct effect of acute in vitro exposure to ethanol was assessed by incubating 15-OH-PGDH with ethanol in the concentration range of 10 to 80 mM. 15-OH-PGDH was measurable in the whole brain and brain stem, and the enzyme activity was similar for the gestational ages examined. There was no significant ethanol-induced inhibition of 15-OH-PGDH activity in the whole brain or brain stem. The data demonstrate that the whole brain and brain stem of the fetal guinea pig have the capacity to metabolize PGE2 to 15-keto-PGE2, an inactive metabolite, during the second half of gestation. The data apparently are not consistent with the hypothesis that acute in vitro exposure to ethanol directly inhibits 15-OH-PGDH activity in fetal brain

  4. Photoacoustic imaging of mesenchymal stem cells in living mice via silica-coated gold nanorods

    Science.gov (United States)

    Jokerst, Jesse V.; Thangaraj, Mridhula; Gambhir, Sanjiv S.

    2014-03-01

    Imaging is crucial for stem cell therapy to monitor the location(s), numbers, and state of the implanted cells. Real-time imaging in particular can ensure proper cell delivery for best engraftment. However, established imaging tools such as MRI are limited by their temporal resolution for guidance during delivery. In contrast, photoacoustic imaging is ideally suited for real time, image-guided therapy. Here, we use silica-coated gold nanorods as photoacoustic contrast agents and deploy them to image and quantitate mesenchymal stem cells during implant into the muscle tissue of live mice. Silica-coated gold nanorods (SiGNRs) were created with standard methods and loaded into mesenchymal stem cells (MSCs) without transfection agents. There was no significant (pmuscle tissue to simulate a muscular dystrophy patient. Mice (N=5) treated with these SiGNRlabeled MSCs exhibited no adverse events and implants up to 5 mm deep were easily visualized. The in vivo detection limit was 90,000 cells in a 100 uL bolus in mouse thigh muscle. Here, the B-mode signal is useful for orienting the treatment area and visualizing the delivery catheter while the photoacoustic mode offers cell-specific content. The photoacoustic signal was validated with histology a long-term fluorescent tracking dye after MSC transplant.

  5. Role of the brain stem in tibial inhibition of the micturition reflex in cats.

    Science.gov (United States)

    Ferroni, Matthew C; Slater, Rick C; Shen, Bing; Xiao, Zhiying; Wang, Jicheng; Lee, Andy; Roppolo, James R; de Groat, William C; Tai, Changfeng

    2015-08-01

    This study examined the role of the brain stem in inhibition of bladder reflexes induced by tibial nerve stimulation (TNS) in α-chloralose-anesthetized decerebrate cats. Repeated cystometrograms (CMGs) were performed by infusing saline or 0.25% acetic acid (AA) to elicit normal or overactive bladder reflexes, respectively. TNS (5 or 30 Hz) at three times the threshold (3T) intensity for inducing toe movement was applied for 30 min between CMGs to induce post-TNS inhibition or applied during the CMGs to induce acute TNS inhibition. Inhibition was evident as an increase in bladder capacity without a change in amplitude of bladder contractions. TNS applied for 30 min between saline CMGs elicited prolonged (>2 h) poststimulation inhibition that significantly (P reflexes but are not involved in inhibition of normal bladder reflexes. Copyright © 2015 the American Physiological Society.

  6. A biomechanical testing system to determine micromotion between hip implant and femur accounting for deformation of the hip implant: Assessment of the influence of rigid body assumptions on micromotions measurements.

    Science.gov (United States)

    Leuridan, Steven; Goossens, Quentin; Roosen, Jorg; Pastrav, Leonard; Denis, Kathleen; Mulier, Michiel; Desmet, Wim; Vander Sloten, Jos

    2017-02-01

    Accurate pre-clinical evaluation of the initial stability of new cementless hip stems using in vitro micromotion measurements is an important step in the design process to assess the new stem's potential. Several measuring systems, linear variable displacement transducer-based and other, require assuming bone or implant to be rigid to obtain micromotion values or to calculate derived quantities such as relative implant tilting. An alternative linear variable displacement transducer-based measuring system not requiring a rigid body assumption was developed in this study. The system combined advantages of local unidirectional and frame-and-bracket micromotion measuring concepts. The influence and possible errors that would be made by adopting a rigid body assumption were quantified. Furthermore, as the system allowed emulating local unidirectional and frame-and-bracket systems, the influence of adopting rigid body assumptions were also analyzed for both concepts. Synthetic and embalmed bone models were tested in combination with primary and revision implants. Single-legged stance phase loading was applied to the implant - bone constructs. Adopting a rigid body assumption resulted in an overestimation of mediolateral micromotion of up to 49.7μm at more distal measuring locations. Maximal average relative rotational motion was overestimated by 0.12° around the anteroposterior axis. Frontal and sagittal tilting calculations based on a unidirectional measuring concept underestimated the true tilting by an order of magnitude. Non-rigid behavior is a factor that should not be dismissed in micromotion stability evaluations of primary and revision femoral implants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. The safety of transcranial magnetic stimulation with deep brain stimulation instruments

    OpenAIRE

    Shimojima, Yoshio; Morita, Hiroshi; Nishikawa, Noriko; Kodaira, Minori; Hashimoto, Takao; Ikeda, Shu-ichi

    2010-01-01

    Objectives: Transcranial magnetic stimulation (TMS) has been employed in patients with an implanted deep brain Stimulation (DBS) device. We investigated the safety of TMS using Simulation models with an implanted DBS device. Methods: The DBS lead was inserted into plastic phantoms filled with dilute gelatin showing impedance similar to that of human brain. TMS was performed with three different types of magnetic coil. During TMS (I) electrode movement, (2) temperature change around the lead, ...

  8. SU-E-T-570: Management of Radiation Oncology Patients with Cochlear Implant and Other Bionic Devices in the Brain and Head and Neck Regions

    Energy Technology Data Exchange (ETDEWEB)

    Guo, F.Q; Chen, Z; Nath, R [Yale New Haven Hospital, New Haven, CT (United States); Yale UniversitySchool of Medicine, New Haven, CT (United States)

    2014-06-01

    Purpose: To investigate the current status of clinical usage of cochlear implant (CI) and other bionic devices (BD) in the brain and head and neck regions (BH and N) and their management in patients during radiotherapy to ensure patient health and safety as well as optimum radiation delivery. Methods: Literature review was performed with both CIs and radiotherapy and their variants as keywords in PubMed, INSPEC and other sources. The focus was on CIs during radiotherapy, but it also included other BDs in BHȦN, such as auditory brainstem implant, bionic retinal implant, and hearing aids, among others. Results: Interactions between CIs and radiation may cause CIs malfunction. The presence of CIs may also cause suboptimum dose distribution if a treatment plan was not well designed. A few studies were performed for the hearing functions of CIs under irradiations of 4 MV and 6 MV x-rays. However, x-rays with higher energies (10 to 18 MV) broadly used in radiotherapy have not been explored. These higher energetic beams are more damaging to electronics due to strong penetrating power and also due to neutrons generated in the treatment process. Modern CIs are designed with more and more complicated integrated circuits, which may be more susceptible to radiation damage and malfunction. Therefore, careful management is important for safety and treatment outcomes. Conclusion: Although AAPM TG-34, TG-63, and TG-203 (update of TG-34, not published yet) reports may be referenced for management of CIs and other BDs in the brain and H and N regions, a site- and device-specified guideline should be developed for CIs and other BDs. Additional evaluation of CI functions under clinically relevant set-ups should also be performed to provide clinicians with better knowledge in clinical decision making.

  9. Controlled Systemic Delivery by Polymeric Implants Enhances Tissue and Plasma Curcumin Levels Compared with Oral Administration

    Science.gov (United States)

    Bansal, Shyam S.; Kausar, Hina; Vadhanam, Manicka V.; Ravoori, Srivani; Gupta, Ramesh C.

    2012-01-01

    Curcumin possess potent anti-inflammatory and anti-proliferative activities but with poor biopharmaceutical attributes. To overcome these limitations, curcumin implants were developed and tissue (plasma, brain and liver) curcumin concentrations were measured in female ACI rats for 3 months. Biological efficacy of tissue levels achieved was analyzed by modulation of hepatic cytochromes. Curcumin implants exhibited diffusion-mediated biphasic release pattern with ~2-fold higher in vivo release as compared to in vitro. Plasma curcumin concentration from implants was ~3.3 ng/ml on day 1 which dropped to ~0.2 ng/ml after 3 months whereas only 0.2–0.3 ng/ml concentration was observed from 4–12 days with diet and was undetected subsequently. Almost 10 fold higher curcumin levels were observed in brain on day 1 from implants compared with diet (30.1±7.3 vs 2.7±0.8 ng/g) and were higher even after 90 days (7.7±3.8 vs 2.2±0.8 ng/g). Although, curcumin levels were similar in liver from both the routes (~25–30 ng/g from day 1–4 and ~10–15 ng/g at 90 days), implants were more efficacious in altering hepatic CYP1A1 levels and CYP3A4 activity at ~28 fold lower doses. Curcumin implants provided much higher plasma and tissue concentrations and are a viable alternative for delivery of curcumin to various organs like brain. PMID:22227368

  10. Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Chung Hyung-Min

    2009-08-01

    Full Text Available Abstract Background Studies have provided important findings about the roles of Notch signaling in neural development. Unfortunately, however, most of these studies have investigated the neural stem cells (NSCs of mice or other laboratory animals rather than humans, mainly owing to the difficulties associated with obtaining human brain samples. It prompted us to focus on neuroectodermal spheres (NESs which are derived from human embryonic stem cell (hESC and densely inhabited by NSCs. We here investigated the role of Notch signaling with the hESC-derived NESs. Results From hESCs, we derived NESs, the in-vitro version of brain-derived neurospheres. NES formation was confirmed by increased levels of various NSC marker genes and the emergence of rosette structures in which neuroprogenitors are known to reside. We found that Notch signaling, which maintains stem cell characteristics of in-vivo-derived neuroprogenitors, is active in these hESC-derived NESs, similar to their in-vivo counterpart. Expression levels of Notch signaling molecules such as NICD, DLLs, JAG1, HES1 and HES5 were increased in the NESs. Inhibition of the Notch signaling by a γ-secretase inhibitor reduced rosette structures, expression levels of NSC marker genes and proliferation potential in the NESs, and, if combined with withdrawal of growth factors, triggered differentiation toward neurons. Conclusion Our results indicate that the hESC-derived NESs, which share biochemical features with brain-derived neurospheres, maintain stem cell characteristics mainly through Notch signaling, which suggests that the hESC-derived NESs could be an in-vitro model for in-vivo neurogenesis.

  11. Mesenchymal stem cells induce T-cell tolerance and protect the preterm brain after global hypoxia-ischemia.

    Directory of Open Access Journals (Sweden)

    Reint K Jellema

    Full Text Available Hypoxic-ischemic encephalopathy (HIE in preterm infants is a severe disease for which no curative treatment is available. Cerebral inflammation and invasion of activated peripheral immune cells have been shown to play a pivotal role in the etiology of white matter injury, which is the clinical hallmark of HIE in preterm infants. The objective of this study was to assess the neuroprotective and anti-inflammatory effects of intravenously delivered mesenchymal stem cells (MSC in an ovine model of HIE. In this translational animal model, global hypoxia-ischemia (HI was induced in instrumented preterm sheep by transient umbilical cord occlusion, which closely mimics the clinical insult. Intravenous administration of 2 x 10(6 MSC/kg reduced microglial proliferation, diminished loss of oligodendrocytes and reduced demyelination, as determined by histology and Diffusion Tensor Imaging (DTI, in the preterm brain after global HI. These anti-inflammatory and neuroprotective effects of MSC were paralleled by reduced electrographic seizure activity in the ischemic preterm brain. Furthermore, we showed that MSC induced persistent peripheral T-cell tolerance in vivo and reduced invasion of T-cells into the preterm brain following global HI. These findings show in a preclinical animal model that intravenously administered MSC reduced cerebral inflammation, protected against white matter injury and established functional improvement in the preterm brain following global HI. Moreover, we provide evidence that induction of T-cell tolerance by MSC might play an important role in the neuroprotective effects of MSC in HIE. This is the first study to describe a marked neuroprotective effect of MSC in a translational animal model of HIE.

  12. Pulmonary heart valve replacement using stabilized acellular xenogeneic scaffolds; effects of seeding with autologous stem cells

    Directory of Open Access Journals (Sweden)

    Harpa Marius Mihai

    2015-12-01

    Full Text Available Background: We hypothesized that an ideal heart valve replacement would be acellular valve root scaffolds seeded with autologous stem cells. To test this hypothesis, we prepared porcine acellular pulmonary valves, seeded them with autologous adipose derived stem cells (ADSCs and implanted them in sheep and compared them to acellular valves.

  13. Derivation of Stromal (Skeletal, Mesenchymal) Stem-like cells from Human Embryonic Stem Cells

    DEFF Research Database (Denmark)

    Mahmood, Amer; Harkness, Linda; Abdallah, Basem

    2012-01-01

    EBs using BMP2 (bone morphogenic protein 2) combined with standard osteoblast induction medium led to weak osteoblastic induction. Conversely, subcutaneous in vivo implantation of day 20 hEBs in immune deficient mice, mixed with hydroxyapatite/tricalcium phosphate (HA/TCP) as an osteoconductive scaffold......Derivation of bone forming cells (osteoblasts) from human embryonic stem cells (hESC) is a pre-requisite for their use in clinical applications. However, there is no standard protocol for differentiating hESC into osteoblastic cells. The aim of this study was to identify the emergence of a human...... stromal (mesenchymal, skeletal) stem cell (hMSC)-like population, known to be osteoblastic cell precursors and to test their osteoblastic differentiation capacity in ex vivo cultures and in vivo. We cultured hESC in a feeder-free environment using serum replacement and as suspension aggregates (embryoid...

  14. Expression and function of orphan nuclear receptor TLX in adult neural stem cells.

    Science.gov (United States)

    Shi, Yanhong; Chichung Lie, D; Taupin, Philippe; Nakashima, Kinichi; Ray, Jasodhara; Yu, Ruth T; Gage, Fred H; Evans, Ronald M

    2004-01-01

    The finding of neurogenesis in the adult brain led to the discovery of adult neural stem cells. TLX was initially identified as an orphan nuclear receptor expressed in vertebrate forebrains and is highly expressed in the adult brain. The brains of TLX-null mice have been reported to have no obvious defects during embryogenesis; however, mature mice suffer from retinopathies, severe limbic defects, aggressiveness, reduced copulation and progressively violent behaviour. Here we show that TLX maintains adult neural stem cells in an undifferentiated, proliferative state. We show that TLX-expressing cells isolated by fluorescence-activated cell sorting (FACS) from adult brains can proliferate, self-renew and differentiate into all neural cell types in vitro. By contrast, TLX-null cells isolated from adult mutant brains fail to proliferate. Reintroducing TLX into FACS-sorted TLX-null cells rescues their ability to proliferate and to self-renew. In vivo, TLX mutant mice show a loss of cell proliferation and reduced labelling of nestin in neurogenic areas in the adult brain. TLX can silence glia-specific expression of the astrocyte marker GFAP in neural stem cells, suggesting that transcriptional repression may be crucial in maintaining the undifferentiated state of these cells.

  15. The vestibular implant: Quo vadis?

    Directory of Open Access Journals (Sweden)

    Raymond eVan De Berg

    2011-08-01

    Full Text Available AbstractObjective: to assess the progress of the development of the vestibular implant and its feasibility short-term. Data sources: a search was performed in Pubmed, Medline and Embase. Key words used were vestibular prosth* and vestibular implant. The only search limit was language: English or Dutch. Additional sources were medical books, conference lectures and our personal experience with per-operative vestibular stimulation in patients selected for cochlear implantation.Study selection: all studies about the vestibular implant and related topics were included and evaluated by two reviewers. No study was excluded since every study investigated different aspects of the vestibular implant. Data extraction and synthesis: data was extracted by the first author from selected reports, supplemented by additional information, medical books conference lectures. Since each study had its own point of interest with its own outcomes, it was not possible to compare data of different studies. Conclusion: to use a basic vestibular implant in humans seems feasible in the very near future. Investigations show that electric stimulation of the canal nerves induces a nystagmus which corresponds to the plane of the canal which is innervated by the stimulated nerve branch. The brain is able to adapt to a higher baseline stimulation, while still reacting on a dynamic component. The best response will be achieved by a combination of the optimal stimulus (stimulus profile, stimulus location, precompensation, complemented by central vestibular adaptation. The degree of response will probably vary between individuals, depending on pathology and their ability to adapt.

  16. In vivo monitoring of glial scar proliferation on chronically implanted neural electrodes by fiber optical coherence tomography

    Science.gov (United States)

    Xie, Yijing; Martini, Nadja; Hassler, Christina; Kirch, Robert D.; Stieglitz, Thomas; Seifert, Andreas; Hofmann, Ulrich G.

    2014-01-01

    In neural prosthetics and stereotactic neurosurgery, intracortical electrodes are often utilized for delivering therapeutic electrical pulses, and recording neural electrophysiological signals. Unfortunately, neuroinflammation impairs the neuron-electrode-interface by developing a compact glial encapsulation around the implants in long term. At present, analyzing this immune reaction is only feasible with post-mortem histology; currently no means for specific in vivo monitoring exist and most applicable imaging modalities can not provide information in deep brain regions. Optical coherence tomography (OCT) is a well established imaging modality for in vivo studies, providing cellular resolution and up to 1.2 mm imaging depth in brain tissue. A fiber based spectral domain OCT was shown to be capable of minimally invasive brain imaging. In the present study, we propose to use a fiber based spectral domain OCT to monitor the progression of the tissue's immune response through scar encapsulation progress in a rat animal model. A fine fiber catheter was implanted in rat brain together with a flexible polyimide microelectrode in sight both of which acts as a foreign body and induces the brain tissue immune reaction. OCT signals were collected from animals up to 12 weeks after implantation and thus gliotic scarring in vivo monitored for that time. Preliminary data showed a significant enhancement of the OCT backscattering signal during the first 3 weeks after implantation, and increased attenuation factor of the sampled tissue due to the glial scar formation. PMID:25191264

  17. Endovascular transplantation of stem cells to the injured rat CNS

    Energy Technology Data Exchange (ETDEWEB)

    Lundberg, Johan; Soederman, Mikael; Andersson, Tommy; Holmin, Staffan [Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Department of Neuroradiology, Stockholm (Sweden); Le Blanc, Katarina [Karolinska University Hospital, Department of Stem Cell Research, Karolinska Institutet, Department of Clinical Immunology, Stockholm (Sweden)

    2009-10-15

    Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells. Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p<0.01) and 5 days (p<0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed. Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases. (orig.)

  18. Endovascular transplantation of stem cells to the injured rat CNS

    International Nuclear Information System (INIS)

    Lundberg, Johan; Soederman, Mikael; Andersson, Tommy; Holmin, Staffan; Le Blanc, Katarina

    2009-01-01

    Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells. Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p<0.01) and 5 days (p<0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed. Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases. (orig.)

  19. Wireless microsensor network solutions for neurological implantable devices

    Science.gov (United States)

    Abraham, Jose K.; Whitchurch, Ashwin; Varadan, Vijay K.

    2005-05-01

    The design and development of wireless mocrosensor network systems for the treatment of many degenerative as well as traumatic neurological disorders is presented in this paper. Due to the advances in micro and nano sensors and wireless systems, the biomedical sensors have the potential to revolutionize many areas in healthcare systems. The integration of nanodevices with neurons that are in communication with smart microsensor systems has great potential in the treatment of many neurodegenerative brain disorders. It is well established that patients suffering from either Parkinson"s disease (PD) or Epilepsy have benefited from the advantages of implantable devices in the neural pathways of the brain to alter the undesired signals thus restoring proper function. In addition, implantable devices have successfully blocked pain signals and controlled various pelvic muscles in patients with urinary and fecal incontinence. Even though the existing technology has made a tremendous impact on controlling the deleterious effects of disease, it is still in its infancy. This paper presents solutions of many problems of today's implantable and neural-electronic interface devices by combining nanowires and microelectronics with BioMEMS and applying them at cellular level for the development of a total wireless feedback control system. The only device that will actually be implanted in this research is the electrodes. All necessary controllers will be housed in accessories that are outside the body that communicate with the implanted electrodes through tiny inductively-coupled antennas. A Parkinson disease patient can just wear a hat-system close to the implantable neural probe so that the patient is free to move around, while the sensors continually monitor, record, transmit all vital information to health care specialist. In the event of a problem, the system provides an early warning to the patient while they are still mobile thus providing them the opportunity to react and

  20. Encapsulated dental-derived mesenchymal stem cells in an injectable and biodegradable scaffold for applications in bone tissue engineering.

    Science.gov (United States)

    Moshaverinia, Alireza; Chen, Chider; Akiyama, Kentaro; Xu, Xingtian; Chee, Winston W L; Schricker, Scott R; Shi, Songtao

    2013-11-01

    Bone grafts are currently the major family of treatment options in modern reconstructive dentistry. As an alternative, stem cell-scaffold constructs seem to hold promise for bone tissue engineering. However, the feasibility of encapsulating dental-derived mesenchymal stem cells in scaffold biomaterials such as alginate hydrogel remains to be tested. The objectives of this study were, therefore, to: (1) develop an injectable scaffold based on oxidized alginate microbeads encapsulating periodontal ligament stem cells (PDLSCs) and gingival mesenchymal stem cells (GMSCs); and (2) investigate the cell viability and osteogenic differentiation of the stem cells in the microbeads both in vitro and in vivo. Microbeads with diameters of 1 ± 0.1 mm were fabricated with 2 × 10(6) stem cells/mL of alginate. Microbeads containing PDLSCs, GMSCs, and human bone marrow mesenchymal stem cells as a positive control were implanted subcutaneously and ectopic bone formation was analyzed by micro CT and histological analysis at 8-weeks postimplantation. The encapsulated stem cells remained viable after 4 weeks of culturing in osteo-differentiating induction medium. Scanning electron microscopy and X-ray diffraction results confirmed that apatitic mineral was deposited by the stem cells. In vivo, ectopic mineralization was observed inside and around the implanted microbeads containing the immobilized stem cells. These findings demonstrate for the first time that immobilization of PDLSCs and GMSCs in alginate microbeads provides a promising strategy for bone tissue engineering. Copyright © 2013 Wiley Periodicals, Inc.