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Sample records for brain stem implant

  1. 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.

  2. 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.

  3. 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

  4. Paraneoplastic brain stem encephalitis.

    Science.gov (United States)

    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.

  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. 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)

  7. 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)

  8. 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)

  9. 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.

  10. 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

  11. 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

  12. 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 ...

  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. 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.

  15. 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.

  16. 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)

  17. 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

  18. 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 ...

  19. 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)

  20. 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.

  1. 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

  2. Aqp 9 and Brain Tumour Stem Cells

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    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.

  3. 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.

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

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    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.

  5. 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.

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

    Science.gov (United States)

    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.

  7. Milrinone in Enterovirus 71 Brain Stem Encephalitis

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    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.

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

    Science.gov (United States)

    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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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...

  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. 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)

  3. 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.

  4. 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...

  5. 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)

  6. 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)

  7. 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.

  8. 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

  9. 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.

  10. 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).

  11. 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.

  12. 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.

  13. 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

  14. 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...

  15. 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.

  16. 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)

  17. 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.

  18. 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)

  19. 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.)

  20. 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...

  1. 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

  2. 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

  3. 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.

  4. 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)

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.)

  12. 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.

  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. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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)

  6. 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

  7. 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.)

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  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. 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).

  17. 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.

  18. 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.

  19. 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...

  20. 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...

  1. 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

  2. [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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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...

  12. 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.

  13. 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.

  14. 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.)

  15. 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 ...

  16. 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.

  17. 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.

  18. 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.

  19. 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 .).

  20. 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

  1. 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

  2. [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.

  3. Cyclosporin safety in a simplified rat brain tumor implantation model

    Directory of Open Access Journals (Sweden)

    Francisco H. C. Felix

    2012-01-01

    Full Text Available Brain cancer is the second neurological cause of death. A simplified animal brain tumor model using W256 (carcinoma 256, Walker cell line was developed to permit the testing of novel treatment modalities. Wistar rats had a cell tumor solution inoculated stereotactically in the basal ganglia (right subfrontal caudate. This model yielded tumor growth in 95% of the animals, and showed absence of extracranial metastasis and systemic infection. Survival median was 10 days. Estimated tumor volume was 17.08±6.7 mm³ on the 7th day and 67.25±19.8 mm³ on 9th day post-inoculation. Doubling time was 24.25 h. Tumor growth induced cachexia, but no hematological or biochemical alterations. This model behaved as an undifferentiated tumor and can be promising for studying tumor cell migration in the central nervous system. Dexamethasone 3.0 mg/kg/day diminished significantly survival in this model. Cyclosporine 10 mg/kg/day administration was safely tolerated.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  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. 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).

  10. 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

  11. 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.

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

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    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

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

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    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

  14. 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.)

  15. 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.

  16. 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

  17. 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)

  18. 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).

  19. 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.

  20. 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.

  1. 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.

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

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    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.

  3. 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.

  4. 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.

  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. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Stem cells and treatment of brain and spinal cord injury

    Czech Academy of Sciences Publication Activity Database

    Syková, Eva

    2009-01-01

    Roč. 276, Suppl.1 (2009), s. 40-40 ISSN 1742-464X. [Congress of the Federation-of-European-Biochemical-Societies /34./. 04.07.2009-09.07.2009, Prague] Institutional research plan: CEZ:AV0Z50390703 Keywords : Stem cells Subject RIV: FH - Neurology

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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)

  17. 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

  18. 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)

  19. 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

  20. 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.

  1. 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.

  2. 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)

  3. 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...

  4. 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

  5. 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.

  6. 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.

  7. 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)

  8. 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).

  9. 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.

  10. 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.)

  11. 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.)

  12. 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.

  13. Me, myself my brain implant : deep brain stimulation raises quistions of personal authenticity and alienation

    NARCIS (Netherlands)

    Kraemer, U.A.F.

    2013-01-01

    In this article, I explore select case studies of Parkinson patients treated with deep brain stimulation (DBS) in light of the notions of alienation and authenticity. While the literature on DBS has so far neglected the issues of authenticity and alienation, I argue that interpreting these cases in

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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...

  19. 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.

  20. 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%.

  1. 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

  2. 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

  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. 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...

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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).

  11. 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...

  12. 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....

  13. 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...

  14. 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.)

  15. 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).

  16. 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)

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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...

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  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. 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

  8. [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.

  9. 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.

  10. 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

  11. 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

  12. 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.

  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. 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.

  15. 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.

  16. Me, Myself and My Brain Implant: Deep Brain Stimulation Raises Questions of Personal Authenticity and Alienation.

    Science.gov (United States)

    Kraemer, Felicitas

    2013-01-01

    In this article, I explore select case studies of Parkinson patients treated with deep brain stimulation (DBS) in light of the notions of alienation and authenticity. While the literature on DBS has so far neglected the issues of authenticity and alienation, I argue that interpreting these cases in terms of these concepts raises new issues for not only the philosophical discussion of neuro-ethics of DBS, but also for the psychological and medical approach to patients under DBS. In particular, I suggest that the experience of alienation and authenticity varies from patient to patient with DBS. For some, alienation can be brought about by neurointerventions because patients no longer feel like themselves. But, on the other hand, it seems alienation can also be cured by DBS as other patients experience their state of mind as authentic under treatment and retrospectively regard their former lives without stimulation as alienated. I argue that we must do further research on the relevance of authenticity and alienation to patients treated with DBS in order to gain a deeper philosophical understanding, and to develop the best evaluative criterion for the behavior of DBS patients.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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...

  2. 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)

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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)

  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. 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

  12. 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

  13. 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

  14. 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.

  15. 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)

  16. 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)

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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...

  4. 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.

  5. 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.)

  6. 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.

  7. 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.

  8. 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...

  9. 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.

  10. 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

  11. Hyaline cartilage formation and tumorigenesis of implanted tissues derived from human induced pluripotent stem cells.

    Science.gov (United States)

    Saito, Taku; Yano, Fumiko; Mori, Daisuke; Kawata, Manabu; Hoshi, Kazuto; Takato, Tsuyoshi; Masaki, Hideki; Otsu, Makoto; Eto, Koji; Nakauchi, Hiromitsu; Chung, Ung-il; Tanaka, Sakae

    2015-01-01

    Induced pluripotent stem cells (iPSCs) are a promising cell source for cartilage regenerative medicine. Meanwhile, the risk of tumorigenesis should be considered in the clinical application of human iPSCs (hiPSCs). Here, we report in vitro chondrogenic differentiation of hiPSCs and maturation of the differentiated hiPSCs through transplantation into mouse knee joints. Three hiPSC clones showed efficient chondrogenic differentiation using an established protocol for human embryonic stem cells. The differentiated hiPSCs formed hyaline cartilage tissues at 8 weeks after transplantation into the articular cartilage of NOD/SCID mouse knee joints. Although tumors were not observed during the 8 weeks after transplantation, an immature teratoma had developed in one mouse at 16 weeks. In conclusion, hiPSCs are a potent cell source for regeneration of hyaline articular cartilage. However, the risk of tumorigenesis should be managed for clinical application in the future.

  12. 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

  13. Skeletal stem cell and bone implant interactions are enhanced by LASER titanium modification

    Energy Technology Data Exchange (ETDEWEB)

    Sisti, Karin E., E-mail: karinellensisti@gmail.com [Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD (United Kingdom); Biomaterials Group, Institute of Chemistry, São Paulo State University (UNESP), Box 355, Araraquara (Brazil); Federal University of Mato Grosso do Sul (UFMS), Campo Grande (Brazil); Andrés, María C. de; Johnston, David [Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD (United Kingdom); Almeida-Filho, Edson; Guastaldi, Antonio C. [Biomaterials Group, Institute of Chemistry, São Paulo State University (UNESP), Box 355, Araraquara (Brazil); Oreffo, Richard O.C. [Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD (United Kingdom)

    2016-05-06

    Purpose: To evaluate the osteo-regenerative potential of Titanium (Ti) modified by Light Amplification by Stimulated Emission of Radiation (LASER) beam (Yb-YAG) upon culture with human Skeletal Stem Cells (hSSCs{sup 1}). Methods: Human skeletal cell populations were isolated from the bone marrow of haematologically normal patients undergoing primary total hip replacement following appropriate consent. STRO-1{sup +} hSSC{sup 1} function was examined for 10 days across four groups using Ti discs: i) machined Ti surface group in basal media (Mb{sup 2}), ii) machined Ti surface group in osteogenic media (Mo{sup 3}), iii) LASER-modified Ti group in basal media (Lb{sup 4}) and, iv) LASER-modified Ti group in osteogenic media (Lo{sup 5}). Molecular analysis and qRT-PCR as well as functional analysis including biochemistry (DNA, Alkaline Phosphatase (ALP{sup 6}) specific activity), live/dead immunostaining (Cell Tracker Green (CTG{sup 7})/Ethidium Homodimer-1 (EH-1{sup 8})), and fluorescence staining (for vinculin and phalloidin) were undertaken. Inverted, confocal and Scanning Electron Microscopy (SEM) approaches were used to characterise cell adherence, proliferation, and phenotype. Results: Enhanced cell spreading and morphological rearrangement, including focal adhesions were observed following culture of hSSCs{sup 1} on LASER surfaces in both basal and osteogenic conditions. Biochemical analysis demonstrated enhanced ALP{sup 6} specific activity on the hSSCs{sup 1}-seeded on LASER-modified surface in basal culture media. Molecular analysis demonstrated enhanced ALP{sup 6} and osteopontin expression on titanium LASER treated surfaces in basal conditions. SEM, inverted microscopy and confocal laser scanning microscopy confirmed extensive proliferation and migration of human bone marrow stromal cells on all surfaces evaluated. Conclusions: LASER-modified Ti surfaces modify the behaviour of hSSCs.{sup 1} In particular, SSC{sup 1} adhesion, osteogenic gene expression, cell

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. Bone marrow mesenchymal stem cells differentiation and proliferation on the surface of coral implant

    International Nuclear Information System (INIS)

    Al-Salihi, K.A.; Samsudin, A.R.

    2004-01-01

    This study was designed to evaluate the ability of natural coral implant to provide an environment for marrow cells to differentiate into osteoblasts and function suitable for mineralized tissue formation. DNA content, alkaline phosptatase (ALP) activity, calcium (Ca) content and mineralized nodules, were measured at day 3, day 7 and day 14, in rat bone marrow stromal cells cultured with coral discs glass discs, while cells alone and coral disc alone cultured as control. DNA content, ALP activity, Ca content measurements showed no difference between coral, glass and cells groups at 3 day which were higher than control (coral disc alone), but there were higher asurement at day 7 and 14 in the cell cultured on coral than on glass discs, control cells and control coral discs. Mineralized nodules formation (both in area and number) was more predominant on the coral surface than in control groups. These results showed that natural coral implant provided excellent and favorable situation for marrow cell to differentiate to osteoblasts, lead to large amount of mineralized tissue formation on coral surface. This in vitro result could explain the rapid bone bonding of coral in vivo. (Author)

  19. 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

  20. [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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  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. 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.)

  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. A Case of Primary Central Nervous System Lymphoma Located at Brain Stem in a Child.

    Science.gov (United States)

    Kim, Jinho; Kim, Young Zoon

    2016-10-01

    Primary central nervous system lymphoma (PCNSL) is an extranodal Non-Hodgkin's lymphoma that is confined to the brain, eyes, and/or leptomeninges without evidence of a systemic primary tumor. Although the tumor can affect all age groups, it is rare in childhood; thus, its incidence and prognosis in children have not been well defined and the best treatment strategy remains unclear. A nine-year old presented at our department with complaints of diplopia, dizziness, dysarthria, and right side hemiparesis. Magnetic resonance image suggested a diffuse brain stem glioma with infiltration into the right cerebellar peduncle. The patient was surgically treated by craniotomy and frameless stereotactic-guided biopsy, and unexpectedly, the histopathology of the mass was consistent with diffuse large B cell lymphoma, and immunohistochemical staining revealed positivity for CD20 and CD79a. Accordingly, we performed a staging work-up for systemic lymphoma, but no evidence of lymphoma elsewhere in the body was obtained. In addition, she had a negative serologic finding for human immunodeficient virus, which confirmed the histopathological diagnosis of PCNSL. She was treated by radiosurgery at 12 Gy and subsequent adjuvant combination chemotherapy based on high dose methotrexate. Unfortunately, 10 months after the tissue-based diagnosis, she succumbed due to an acute hydrocephalic crisis.

  1. Transmigration of neural stem cells across the blood brain barrier induced by glioma cells.

    Directory of Open Access Journals (Sweden)

    Mónica Díaz-Coránguez

    Full Text Available Transit of human neural stem cells, ReNcell CX, through the blood brain barrier (BBB was evaluated in an in vitro model of BBB and in nude mice. The BBB model was based on rat brain microvascular endothelial cells (RBMECs cultured on Millicell inserts bathed from the basolateral side with conditioned media (CM from astrocytes or glioma C6 cells. Glioma C6 CM induced a significant transendothelial migration of ReNcells CX in comparison to astrocyte CM. The presence in glioma C6 CM of high amounts of HGF, VEGF, zonulin and PGE2, together with the low abundance of EGF, promoted ReNcells CX transmigration. In contrast cytokines IFN-α, TNF-α, IL-12p70, IL-1β, IL-6, IL-8 and IL-10, as well as metalloproteinases -2 and -9 were present in equal amounts in glioma C6 and astrocyte CMs. ReNcells expressed the tight junction proteins occludin and claudins 1, 3 and 4, and the cell adhesion molecule CRTAM, while RBMECs expressed occludin, claudins 1 and 5 and CRTAM. Competing CRTAM mediated adhesion with soluble CRTAM, inhibited ReNcells CX transmigration, and at the sites of transmigration, the expression of occludin and claudin-5 diminished in RBMECs. In nude mice we found that ReNcells CX injected into systemic circulation passed the BBB and reached intracranial gliomas, which overexpressed HGF, VEGF and zonulin/prehaptoglobin 2.

  2. Transmigration of neural stem cells across the blood brain barrier induced by glioma cells.

    Science.gov (United States)

    Díaz-Coránguez, Mónica; Segovia, José; López-Ornelas, Adolfo; Puerta-Guardo, Henry; Ludert, Juan; Chávez, Bibiana; Meraz-Cruz, Noemi; González-Mariscal, Lorenza

    2013-01-01

    Transit of human neural stem cells, ReNcell CX, through the blood brain barrier (BBB) was evaluated in an in vitro model of BBB and in nude mice. The BBB model was based on rat brain microvascular endothelial cells (RBMECs) cultured on Millicell inserts bathed from the basolateral side with conditioned media (CM) from astrocytes or glioma C6 cells. Glioma C6 CM induced a significant transendothelial migration of ReNcells CX in comparison to astrocyte CM. The presence in glioma C6 CM of high amounts of HGF, VEGF, zonulin and PGE2, together with the low abundance of EGF, promoted ReNcells CX transmigration. In contrast cytokines IFN-α, TNF-α, IL-12p70, IL-1β, IL-6, IL-8 and IL-10, as well as metalloproteinases -2 and -9 were present in equal amounts in glioma C6 and astrocyte CMs. ReNcells expressed the tight junction proteins occludin and claudins 1, 3 and 4, and the cell adhesion molecule CRTAM, while RBMECs expressed occludin, claudins 1 and 5 and CRTAM. Competing CRTAM mediated adhesion with soluble CRTAM, inhibited ReNcells CX transmigration, and at the sites of transmigration, the expression of occludin and claudin-5 diminished in RBMECs. In nude mice we found that ReNcells CX injected into systemic circulation passed the BBB and reached intracranial gliomas, which overexpressed HGF, VEGF and zonulin/prehaptoglobin 2.

  3. 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...

  4. Regional Susceptibility to Domoic Acid in Primary Astrocyte Cells Cultured from the Brain Stem and Hippocampus

    Directory of Open Access Journals (Sweden)

    Olga M. Pulido

    2008-02-01

    Full Text Available Domoic acid is a marine biotoxin associated with harmful algal blooms and is the causative agent of amnesic shellfish poisoning in marine animals and humans. It is also an excitatory amino acid analog to glutamate and kainic acid which acts through glutamate receptors eliciting a very rapid and potent neurotoxic response. The hippocampus, among other brain regions, has been identified as a specific target site having high sensitivity to DOM toxicity. Histopathology evidence indicates that in addition to neurons, the astrocytes were also injured. Electron microscopy data reported in this study further supports the light microscopy findings. Furthermore, the effect of DOM was confirmed by culturing primary astrocytes from the hippocampus and the brain stem and subsequently exposing them to domoic acid. The RNA was extracted and used for biomarker analysis. The biomarker analysis was done for the early response genes including c-fos, c-jun, c-myc, Hsp-72; specific marker for the astrocytes- GFAP and the glutamate receptors including GluR 2, NMDAR 1, NMDAR 2A and B. Although, the astrocyte-GFAP and c-fos were not affected, c-jun and GluR 2 were down-regulated. The microarray analysis revealed that the chemokines / cytokines, tyrosine kinases (Trk, and apoptotic genes were altered. The chemokines that were up-regulated included - IL1-a, IL-1B, IL-6, the small inducible cytokine, interferon protein IP-10, CXC chemokine LIX, and IGF binding proteins. The Bax, Bcl-2, Trk A and Trk B were all downregulated. Interestingly, only the hippocampal astrocytes were affected. Our findings suggest that astrocytes may present a possible target for pharmacological interventions for the prevention and treatment of amnesic shellfish poisoning and for other brain pathologies involving excitotoxicity

  5. 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.

  6. 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.

  7. 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.

  8. Efficient and Rapid Derivation of Primitive Neural Stem Cells and Generation of Brain Subtype Neurons From Human Pluripotent Stem Cells

    OpenAIRE

    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.

    2013-01-01

    This study developed a highly efficient serum-free pluripotent stem cell (PSC) neural induction medium that can induce human PSCs into primitive neural stem cells (NSCs) in 7 days, obviating the need for time-consuming, laborious embryoid body generation or rosette picking. This method of primitive NSC derivation sets the stage for the scalable production of clinically relevant neural cells for cell therapy applications in good manufacturing practice conditions.

  9. Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model.

    Directory of Open Access Journals (Sweden)

    Emerson C Perin

    Full Text Available The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [(18F]FEAU to monitor the long-term (up to 5 months spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [(18F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33-35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC-associated [(18F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [(18F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI.

  10. A phase I trial of etanidazole and hyperfractionated radiotherapy in children with diffuse brain stem glioma

    International Nuclear Information System (INIS)

    Dutton, S.C.; Pomeroy, S.L.; Billett, A.L.; Barnes, P.; Kuhlman, C.; Riese, N.E.; Goumnerova, L.; Scott, R.M.; Coleman, C.N.; Tarbell, N.J.

    1997-01-01

    Objective: Prospective phase I study to evaluate the toxicity and maximum tolerated dose of etanidazole administered concurrently with hyperfractionated radiation therapy (HRT) for children with brain stem glioma. Materials and Methods: Eighteen patients with brain stem glioma were treated with etanidazole and HRT from 1990-1996. Eligibility required MRI confirmation of diffuse glioma of medulla, pons or mesencephalon, and signs/symptoms of cranial nerve deficit, ataxia or long tract signs of ≤ 6 months duration. Cervico-medullary tumors were excluded. Patients (median age 8.5 years; 11 males, 7 females) received HRT to the tumor volume plus a 2 cm margin with parallel opposed 6-15 MV photons. The total dose was 66 Gy for the first 3 patients, followed by 63 Gy over 4.2 weeks (1.5 Gy BID with 6 hours between fractions) for the subsequent 15 patients. Etanidazole was administered as a rapid IV infusion 30 minutes prior to the morning fraction of HRT at doses of 1.8 gm/m2 x 17 doses (30.6 gm/m2) at step 1 to a maximum of 2.4 gm/m2 x 21 doses (50.4 gm/m2) at step 8. Dose escalation was planned with 3 patients at each of the 8 levels. Results: Three patients were treated at each dose level except level 2, on which only one patient was treated. The highest dose level achieved was step 7 which delivered a total etanidazole dose of 46.2 gm/m2. Two patients were treated at this level, and both patients experienced grade 3 toxicity in the form of a diffuse cutaneous rash. Three patients received a lower dose of 42 gm/m2 without significant toxicity, and this represents the maximum tolerated dose (MTD). There were 24 cases of grade 1 toxicity (10 vomiting, 5 peripheral neuropathy, 2 rash, 2 constipation, 1 skin erythema, 1 weight loss, 3 other), eleven cases of grade 2 toxicity (4 vomiting, 2 skin erythema, 2 constipation, 1 arthalgia, 1 urinary retention, 1 hematologic), and four grade b 3 toxicities (2 rash, 1 vomiting, 1 skin desquamation). Grade 2 or 3 peripheral

  11. Metformin and Ara-a Effectively Suppress Brain Cancer by Targeting Cancer Stem/Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Tarek H. Mouhieddine

    2015-11-01

    Full Text Available Background: Gliomas and neuroblastomas pose a great health burden worldwide with a poor and moderate prognosis, respectively. Many studies have tried to find effective treatments for these primary malignant brain tumors. Of interest, the AMP-activated protein kinase (AMPK pathway was found to be associated with tumorigenesis and tumor survival, leading to many studies on AMPK drugs, especially Metformin, and their potential role as anti-cancer treatments. Cancer stem cells (CSCs are a small population of slowly-dividing, treatment-resistant, undifferentiated cancer cells that are being discovered in a multitude of cancers. They are thought to be responsible for replenishing the tumor with highly proliferative cells and increasing the risk of recurrence. Methods: Metformin and 9-β-d-Arabinofuranosyl Adenine (Ara-a were used to study the role of the AMPK pathway in vitro on U251 (glioblastoma and SHSY-5Y (neuroblastoma cell lines.Results: We found that both drugs are able to decrease the survival of U251 and SH-SY5Y cell lines in a 2D as well as a 3D culture model. Metformin and Ara-a significantly decreased the invasive ability of these cancer cell lines. Treatment with these drugs decreased the sphere-forming units (SFU of U251 cells, with Ara-a being more efficient, signifying the extinction of the CSC population. However, if treatment is withdrawn before all SFUs are extinguished, the CSCs regain some of their sphere-forming capabilities in the case of Metformin but not Ara-a treatment. Conclusion: Metformin and Ara-a have proved to be effective in the treatment of glioblastomas and neuroblastomas, in vitro, by targeting their cancer stem/progenitor cell population, which prevents recurrence.

  12. 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.

  13. Accelerated differentiation of human induced pluripotent stem cells to blood-brain barrier endothelial cells.

    Science.gov (United States)

    Hollmann, Emma K; Bailey, Amanda K; Potharazu, Archit V; Neely, M Diana; Bowman, Aaron B; Lippmann, Ethan S

    2017-04-13

    Due to their ability to limitlessly proliferate and specialize into almost any cell type, human induced pluripotent stem cells (iPSCs) offer an unprecedented opportunity to generate human brain microvascular endothelial cells (BMECs), which compose the blood-brain barrier (BBB), for research purposes. Unfortunately, the time, expense, and expertise required to differentiate iPSCs to purified BMECs precludes their widespread use. Here, we report the use of a defined medium that accelerates the differentiation of iPSCs to BMECs while achieving comparable performance to BMECs produced by established methods. Induced pluripotent stem cells were seeded at defined densities and differentiated to BMECs using defined medium termed E6. Resultant purified BMEC phenotypes were assessed through trans-endothelial electrical resistance (TEER), fluorescein permeability, and P-glycoprotein and MRP family efflux transporter activity. Expression of endothelial markers and their signature tight junction proteins were confirmed using immunocytochemistry. The influence of co-culture with astrocytes and pericytes on purified BMECs was assessed via TEER measurements. The robustness of the differentiation method was confirmed across independent iPSC lines. The use of E6 medium, coupled with updated culture methods, reduced the differentiation time of iPSCs to BMECs from thirteen to 8 days. E6-derived BMECs expressed GLUT-1, claudin-5, occludin, PECAM-1, and VE-cadherin and consistently achieved TEER values exceeding 2500 Ω × cm 2 across multiple iPSC lines, with a maximum TEER value of 4678 ± 49 Ω × cm 2 and fluorescein permeability below 1.95 × 10 -7 cm/s. E6-derived BMECs maintained TEER above 1000 Ω × cm 2 for a minimum of 8 days and showed no statistical difference in efflux transporter activity compared to BMECs differentiated by conventional means. The method was also found to support long-term stability of BMECs harboring biallelic PARK2 mutations associated

  14. 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.

  15. Atomic layer deposited TiO{sub 2} for implantable brain-chip interfacing devices

    Energy Technology Data Exchange (ETDEWEB)

    Cianci, E., E-mail: elena.cianci@mdm.imm.cnr.it [Laboratorio MDM, IMM-CNR, 20864 Agrate Brianza (MB) (Italy); Lattanzio, S. [Istituto di Fisiologia, Dipartimento di Anatomia Umana e Fisiologia, Universita di Padova, 35131 Padova (Italy); Dipartimento di Ingegneria dell' Informazione, Universita di Padova, 35131 Padova (Italy); Seguini, G. [Laboratorio MDM, IMM-CNR, 20864 Agrate Brianza (Italy); Vassanelli, S. [Istituto di Fisiologia, Dipartimento di Anatomia Umana e Fisiologia, Universita di Padova, 35131 Padova (Italy); Fanciulli, M. [Laboratorio MDM, IMM-CNR, 20864 Agrate Brianza (Italy); Dipartimento di Scienza dei Materiali, Universita degli Studi di Milano-Bicocca, 20126 Milano (Italy)

    2012-05-01

    In this paper we investigated atomic layer deposition (ALD) TiO{sub 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 Degree-Sign 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{sub 2}O{sub 3} buffer layer between TiO{sub 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.

  16. 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.

  17. Presenilins are required for maintenance of neural stem cells in the developing brain

    Directory of Open Access Journals (Sweden)

    Kim Woo-Young

    2008-01-01

    Full Text Available Abstract The early embryonic lethality of mutant mice bearing germ-line deletions of both presenilin genes precluded the study of their functions in neural development. We therefore employed the Cre-loxP technology to generate presenilin conditional double knockout (PS cDKO mice, in which expression of both presenilins is inactivated in neural progenitor cells (NPC or neural stem cells and their derivative neurons and glia beginning at embryonic day 11 (E11. In PS cDKO mice, dividing NPCs labeled by BrdU are decreased in number beginning at E13.5. By E15.5, fewer than 20% of NPCs remain in PS cDKO mice. The depletion of NPCs is accompanied by severe morphological defects and hemorrhages in the PS cDKO embryonic brain. Interkinetic nuclear migration of NPCs is also disrupted in PS cDKO embryos, as evidenced by displacement of S-phase and M-phase nuclei in the ventricular zone of the telencephalon. Furthermore, the depletion of neural progenitor cells in PS cDKO embryos is due to NPCs exiting cell cycle and differentiating into neurons rather than reentering cell cycle between E13.5 and E14.5 following PS inactivation in most NPCs. The length of cell cycle, however, is unchanged in PS cDKO embryos. Expression of Notch target genes, Hes1 and Hes5, is significantly decreased in PS cDKO brains, whereas Dll1 expression is up-regulated, indicating that Notch signaling is effectively blocked by PS inactivation. These findings demonstrate that presenilins are essential for neural progenitor cells to re-enter cell cycle and thus ensure proper expansion of neural progenitor pool during embryonic neural development.

  18. Intranasal mesenchymal stem cell treatment for neonatal brain damage: long-term cognitive and sensorimotor improvement.

    Directory of Open Access Journals (Sweden)

    Vanessa Donega

    Full Text Available Mesenchymal stem cell (MSC administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic window and dose response relationships. Furthermore, the appearance of MSCs at the lesion site in relation to the therapeutic window was examined. Nine-day-old mice were subjected to unilateral carotid artery occlusion and hypoxia. MSCs were administered intranasally at 3, 10 or 17 days after hypoxia-ischemia (HI. Motor, cognitive and histological outcome was investigated. PKH-26 labeled cells were used to localize MSCs in the brain. We identified 0.5 × 10(6 MSCs as the minimal effective dose with a therapeutic window of at least 10 days but less than 17 days post-HI. A single dose was sufficient for a marked beneficial effect. MSCs reach the lesion site within 24 h when given 3 or 10 days after injury. However, no MSCs were detected in the lesion when administered 17 days following HI. We also show for the first time that intranasal MSC treatment after HI improves cognitive function. Improvement of sensorimotor function and histological outcome was maintained until at least 9 weeks post-HI. The capacity of MSCs to reach the lesion site within 24 h after intranasal administration at 10 days but not at 17 days post-HI indicates a therapeutic window of at least 10 days. Our data strongly indicate that intranasal MSC treatment may become a promising non-invasive therapeutic tool to effectively reduce neonatal encephalopathy.

  19. Therapy of brain stem tumors - palliative conception with prospect of curative success

    International Nuclear Information System (INIS)

    Bamberg, M.; Budach, V.; Clar, H.E.; Schmitt, G.

    1984-01-01

    From 1969 to 1981, 23 patients with tumors in the pons region were irradiated at the Department of Radiotherapy of the West German Tumor Center in Essen. The age of the patients ranged from 18 months to 50 years. Fifteen patients (65%) were younger than 18 years, one was 25 years old, and seven were between 40 and 50 years old. In two cases the histologic diagnosis of an astrocytoma I and astrocytoma II could be confirmed by exploratory excision and cyst punction, respectively. Nineteen patients received a shunt system (ventriculoatrial shunt) prior to radiotherapy in order to achieve a pressure reduction. After a follow-up period of 1.5 to 12 years, eleven patients are alive, and twelve patients died from a local recurrence or from progressive tumor growth. The five-year survival rate is 47%. Five of the surviving patients show no or only slight adverse effects on their general condition and are able to attend school or carry out their profession (in Karnofsky: 90 to 100%). Four other patients suffering from marked remaining neurologic symptoms are able to take care of themselves (Karnofsky: 70 to 80%). Two patients need permanent nursing (Karnofsky: 50 to 60%). Because of the local propagation tendency of pons tumors, radiotherapy should be locally restricted to the brain stem and the adjacent brain structures, e.g. cerebellum and proximal neck marrow. The authors recommend target volumes of 55 to 60 Gy, which must be applied within 6 to 8 weeks, taking into account the age of patients. This palliative therapy conception should be applied routinely in the hope of bringing about a curative treatment to this group of patients. (orig.) [de

  20. 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-...

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. Molecular control of brain size: Regulators of neural stem cell life, death and beyond

    International Nuclear Information System (INIS)

    Joseph, Bertrand; Hermanson, Ola

    2010-01-01

    The proper development of the brain and other organs depends on multiple parameters, including strictly controlled expansion of specific progenitor pools. The regulation of such expansion events includes enzymatic activities that govern the correct number of specific cells to be generated via an orchestrated control of cell proliferation, cell cycle exit, differentiation, cell death etc. Certain proteins in turn exert direct control of these enzymatic activities and thus progenitor pool expansion and organ size. The members of the Cip/Kip family (p21Cip1/p27Kip1/p57Kip2) are well-known regulators of cell cycle exit that interact with and inhibit the activity of cyclin-CDK complexes, whereas members of the p53/p63/p73 family are traditionally associated with regulation of cell death. It has however become clear that the roles for these proteins are not as clear-cut as initially thought. In this review, we discuss the roles for proteins of the Cip/Kip and p53/p63/p73 families in the regulation of cell cycle control, differentiation, and death of neural stem cells. We suggest that these proteins act as molecular interfaces, or 'pilots', to assure the correct assembly of protein complexes with enzymatic activities at the right place at the right time, thereby regulating essential decisions in multiple cellular events.

  10. Molecular control of brain size: Regulators of neural stem cell life, death and beyond

    Energy Technology Data Exchange (ETDEWEB)

    Joseph, Bertrand [Department of Oncology-Pathology, Cancer Centrum Karolinska (CCK), Karolinska Institutet, Stockholm (Sweden); Hermanson, Ola, E-mail: ola.hermanson@ki.se [Linnaeus Center in Developmental Biology for Regenerative Medicine (DBRM), Department of Neuroscience, Karolinska Institutet, Stockholm (Sweden)

    2010-05-01

    The proper development of the brain and other organs depends on multiple parameters, including strictly controlled expansion of specific progenitor pools. The regulation of such expansion events includes enzymatic activities that govern the correct number of specific cells to be generated via an orchestrated control of cell proliferation, cell cycle exit, differentiation, cell death etc. Certain proteins in turn exert direct control of these enzymatic activities and thus progenitor pool expansion and organ size. The members of the Cip/Kip family (p21Cip1/p27Kip1/p57Kip2) are well-known regulators of cell cycle exit that interact with and inhibit the activity of cyclin-CDK complexes, whereas members of the p53/p63/p73 family are traditionally associated with regulation of cell death. It has however become clear that the roles for these proteins are not as clear-cut as initially thought. In this review, we discuss the roles for proteins of the Cip/Kip and p53/p63/p73 families in the regulation of cell cycle control, differentiation, and death of neural stem cells. We suggest that these proteins act as molecular interfaces, or 'pilots', to assure the correct assembly of protein complexes with enzymatic activities at the right place at the right time, thereby regulating essential decisions in multiple cellular events.

  11. Neural stem cells show bidirectional experience-dependent plasticity in the perinatal mammalian brain.

    Science.gov (United States)

    Kippin, Tod E; Cain, Sean W; Masum, Zahra; Ralph, Martin R

    2004-03-17

    Many of the effects of prenatal stress on the endocrine function, brain morphology, and behavior in mammals can be reversed by brief sessions of postnatal separation and handling. We have tested the hypothesis that the effects of both the prenatal and postnatal experiences are mediated by negative and positive regulation of neural stem cell (NSC) number during critical stages in neurodevelopment. We used the in vitro clonal neurosphere assay to quantify NSCs in hamsters that had experienced prenatal stress (maternal restraint stress for 2 hr per day, for the last 7 d of gestation), postnatal handling (maternal-offspring separation for 15 min per day during postnatal days 1-21), orboth. Prenatal stress reduced the number of NSCs derived from the subependyma of the lateral ventricle. The effect was already present at postnatal day 1 and persisted into adulthood (at least 14 months of age). Similarly, prenatal stress reduced in vivo proliferation in the adult subependyma of the lateral ventricle. Conversely, postnatal handling increased NSC number and reversed the effect of prenatal stress. The effects of prenatal stress on NSCs and proliferation and the effect of postnatal handling on NSCs did not differ between male and females. The findings demonstrate that environmental factors can produce changes in NSC number that are present at birth and endure into late adulthood. These changes may underlie some of the behavioral effects produced by prenatal stress and postnatal handling.

  12. 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.

  13. 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)

  14. 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 ...

  15. 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

  16. 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…

  17. Brain response to a rhythm deviant in adolescent cochlear implant users before and after an intensive musical training program

    DEFF Research Database (Denmark)

    Petersen, Bjørn; Weed, Ethan; Hansen, Mads

    . This study aimed to investigate auditory brain processing of musical sounds relevant to prosody processing in adolescent CI-users who have received their implant in childhood. Furthermore, we aimed to investigate the potential impact of intensive musical training on adolescent CI-users’ discrimination...... studies have investigated perception of music, prosody, and speech in the growing population of adolescent CI users with a congenital HL. However, recent studies indicate that to keep pace with their normal hearing (NH) peers, supplementary measures of rehabilitation are important throughout adolescence...... of music and speech prosody. Here we present preliminary analyses of ERP responses to rhythmically deviant stimuli and present results from a behavioral rhythm discrimination test. Eleven adolescent CI users (M.age = 17 years) participated in a group-based music training program, consisting of active music...

  18. 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.

  19. 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

  20. 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.

  1. 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...

  2. 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

  3. Assessment of cardiotoxicity during haemopoietic stem cell transplantation with plasma brain natriuretic peptide.

    Science.gov (United States)

    Snowden, J A; Hill, G R; Hunt, P; Carnoutsos, S; Spearing, R L; Espiner, E; Hart, D N

    2000-08-01

    Cardiac failure is a known complication of haemopoietic stem cell transplantation (HSCT) and is often difficult to diagnose as patients may have multiple medical problems. Since brain natriuretic peptide (BNP) is largely a hormone of cardiac ventricular origin and is released early in the course of ventricular dysfunction, we have examined the value of serial plasma BNP levels for detecting cardiac failure in patients undergoing cytotoxic conditioning for HSCT. Fifteen patients undergoing HSCT were evaluated (10 undergoing autologous HSCT; five undergoing allogeneic HSCT). BNP was measured by radioimmunoassay prior to therapy and weekly for 5 weeks. Seven patients had a significant rise in BNP level (above a previously established threshold of 43 pmol/l associated with cardiac failure), occurring 1-4 weeks post commencement of conditioning. In three of these patients, cardiac failure was subsequently diagnosed clinically 3, 9 and 23 days after a BNP level of 43 pmol/l had been detected. These three patients had the highest peak BNP levels for the group and in each case elevation in BNP level occurred for a period exceeding 1 week. Although numbers were relatively small, a BNP >43 pmol/l was significantly associated with the inclusion of high-dose cyclophosphamide in the preparative regimen (P = 0.02). BNP levels showed no relationship to febrile episodes. In conclusion, these results show that plasma BNP may be used as a marker for early detection of cardiac dysfunction in patients undergoing HSCT, particularly if levels are increased for periods exceeding 1 week. Measurement of BNP during HSCT may be helpful in patients at risk of cardiac failure, in complex clinical situations and in monitoring the cardiotoxicity of preparative regimens.

  4. 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.

  5. Repair of the myocardium infarct, with intracoronary implant of mother cells (stem cells) precocious improvement of the ventricular function and the ischemy (first reports of the TECELCOR report)

    International Nuclear Information System (INIS)

    Fernandez Vina, Roberto; Vrsalovic, Francisco; Andrin, Oberdan and others

    2004-01-01

    Twenty patients who suffered extensive anterior myocardial infarction with an evolution of 5 to 72 hours were submitted to a primary PTCA with Stent. The ventricular ejection fraction oscillated between 21 to 30% in correlation to the bidimensional echocardiography. Between the 7th and 12th day, mononuclear CD 34(+) and CD 38(-) cells extracted from the patient's bone marrow were implanted through the anterior descendent coronary artery, with occlusion of the anterior coronary vein, in an average amount of 22 x 10 P6. echocardiographic controls were performed each 7 days until 60 days, noticing a progressive increment in the ejection fraction (EF) from 25 to 45% in the first 60 days, and an improvement of the EF up to 80% after 90 days. Between 90 and 120 days after, a coronary ventriculography was performed, and the permeability of all the implanted stents and an improvement of the EF up to 80% with respect to the basal EF, were observed. The Spect studies were negative with negative ergonometry at 700 kgm. This group of patients was comparing red with 16 patients who were submitted only to primary PTCA with Stent. They had an increase of only 45% of the EF respect to the basal one in the next 90 days and 12 % presented restenosis. Stems cells implant improves the left ventricular performance after a myocardial infarction and it seems to avoid the coronary post-restenosis

  6. 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.

  7. 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

  8. 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)

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. Electroresponsive properties and membrane potential trajectories of three types of inspiratory neurons in the newborn mouse brain stem in vitro

    DEFF Research Database (Denmark)

    Rekling, J C; Champagnat, J; Denavit-Saubié, M

    1996-01-01

    with the aim of extending the classification of inspiratory neurons to include analysis of active membrane properties. 2. The slice generated a regular rhythmic motor output recorded as burst of action potentials on a XII nerve root with a peak to peak time of 11.5 +/- 3.4 s and a duration of 483 +/- 54 ms......1. The electrophysiological properties of inspiratory neurons were studied in a rhythmically active thick-slice preparation of the newborn mouse brain stem maintained in vitro. Whole cell patch recordings were performed from 60 inspiratory neurons within the rostral ventrolateral part of the slice...

  16. 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...

  17. 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

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Overexpression of HIF-1α in mesenchymal stem cells contributes to repairing hypoxic-ischemic brain damage in rats.

    Science.gov (United States)

    Lin, Deju; Zhou, Liping; Wang, Biao; Liu, Lizhen; Cong, Li; Hu, Chuanqin; Ge, Tingting; Yu, Qin

    2017-01-01

    Preclinical researches on mesenchymal stem cells (MSCs) transplantation, which is used to treat hypoxic-ischemic (HI) brain damage, have received inspiring achievements. However, the insufficient migration of active cells to damaged tissues has limited their potential therapeutic effects. There are some evidences that hypoxia inducible factor-1 alpha (HIF-1α) promotes the viability and migration of the cells. Here, we aim to investigate whether overexpression of HIF-1α in MSCs could improve the viability and migration capacity of cells, and its therapeutic efficiency on HI brain damage. In the study, MSCs with HIF-1α overexpression was achieved by recombinant lentiviral vector and transplanted to the rats subsequent to HI. Our data indicated that overexpression of HIF-1α promoted the viability and migration of MSCs, HIF-1α overexpressed MSCs also had a stronger therapeutic efficiency on HI brain damaged treatment by mitigating the injury on behavioral and histological changes evoked by HI insults, accompanied with more MSCs migrating to cerebral damaged area. This study demonstrated that HIF-1α overexpression could increase the MSCs' therapeutic efficiency in HI and the promotion of the cells' directional migration to cerebral HI area by overexpression may be responsible for it, which showed that transplantation of MSCs with HIF-1α overexpression is an attractive therapeutic option to treat HI-induced brain injury in the future. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  1. 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.

  2. 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.

  3. 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.

  4. 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

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

    OpenAIRE

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

    2013-01-01

    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 strategie...

  6. 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.

  7. Bioreactivity: Studies on a Simple Brain Stem Reflex in Behaving Animals

    Science.gov (United States)

    1990-01-04

    attempting to understand complex physiological processes, such as brain neuromodulation , or complex behavioral processes, such as arousal, is finding a...one synapse in brain, and receives dense inputs from two neurochemical systems important in neuromodulation and arousal. Initial pharmacologic studies

  8. 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.

  9. 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.

  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. 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.

  12. Severe encephalopathy after high-dose chemotherapy with autologous stem cell support for brain tumours

    NARCIS (Netherlands)

    van den Berkmortel, F.; Gidding, C.; de Kanter, M.; Punt, C. J. A.

    2006-01-01

    Recurrent medulloblastoma carries a poor prognosis. Long-term survival has been obtained with high-dose chemotherapy with autologous stem cell transplantation and secondary irradiation. A 21-year-old woman with recurrent medulloblastoma after previous chemotherapy and radiotherapy is presented. The

  13. Keeping Disability in Mind: A Case Study in Implantable Brain-Computer Interface Research.

    Science.gov (United States)

    Sullivan, Laura Specker; Klein, Eran; Brown, Tim; Sample, Matthew; Pham, Michelle; Tubig, Paul; Folland, Raney; Truitt, Anjali; Goering, Sara

    2018-04-01

    Brain-Computer Interface (BCI) research is an interdisciplinary area of study within Neural Engineering. Recent interest in end-user perspectives has led to an intersection with user-centered design (UCD). The goal of user-centered design is to reduce the translational gap between researchers and potential end users. However, while qualitative studies have been conducted with end users of BCI technology, little is known about individual BCI researchers' experience with and attitudes towards UCD. Given the scientific, financial, and ethical imperatives of UCD, we sought to gain a better understanding of practical and principled considerations for researchers who engage with end users. We conducted a qualitative interview case study with neural engineering researchers at a center dedicated to the creation of BCIs. Our analysis generated five themes common across interviews. The thematic analysis shows that participants identify multiple beneficiaries of their work, including other researchers, clinicians working with devices, device end users, and families and caregivers of device users. Participants value experience with device end users, and personal experience is the most meaningful type of interaction. They welcome (or even encourage) end-user input, but are skeptical of limited focus groups and case studies. They also recognize a tension between creating sophisticated devices and developing technology that will meet user needs. Finally, interviewees espouse functional, assistive goals for their technology, but describe uncertainty in what degree of function is "good enough" for individual end users. Based on these results, we offer preliminary recommendations for conducting future UCD studies in BCI and neural engineering.

  14. 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.

  15. Pivotal Role of Brain-Derived Neurotrophic Factor Secreted by Mesenchymal Stem Cells in Severe Intraventricular Hemorrhage in Newborn Rats.

    Science.gov (United States)

    Ahn, So Yoon; Chang, Yun Sil; Sung, Dong Kyung; Sung, Se In; Ahn, Jee-Yin; Park, Won Soon

    2017-01-24

    Mesenchymal stem cell (MSC) transplantation protects against neonatal severe intraventricular hemorrhage (IVH)-induced brain injury by a paracrine rather than regenerative mechanism; however, the paracrine factors involved and their roles have not yet been delineated. This study aimed to identify the paracrine mediator(s) and to determine their role in mediating the therapeutic effects of MSCs in severe IVH. We first identified significant upregulation of brain-derived neurotrophic factor (BDNF) in MSCs compared with fibroblasts, in both DNA and antibody microarrays, after thrombin exposure. We then knocked down BDNF in MSCs by transfection with small interfering (si)RNA specific for human BDNF. The therapeutic effects of MSCs with or without BDNF knockdown were evaluated in vitro in rat neuronal cells challenged with thrombin, and in vivo in newborn Sprague-Dawley rats by injecting 200 μl of blood on postnatal day 4 (P4), and transplanting MSCs (1 × 105 cells) intraventricularly on P6. siRNA-induced BDNF knockdown abolished the in vitro benefits of MSCs on thrombin-induced neuronal cell death. BDNF knockdown also abolished the in vivo protective effects against severe IVH-induced brain injuries such as the attenuation of posthemorrhagic hydrocephalus, impaired behavioral test performance, increased astrogliosis, increased number of TUNEL cells, ED-1+ cells, and inflammatory cytokines, and reduced myelin basic protein expression. Our data indicate that BDNF secreted by transplanted MSCs is one of the critical paracrine factors that play a seminal role in attenuating severe IVH-induced brain injuries in newborn rats.

  16. 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.

  17. Thyrotropin-releasing hormone (TRH) depolarizes a subset of inspiratory neurons in the newborn mouse brain stem in vitro

    DEFF Research Database (Denmark)

    Rekling, J C; Champagnat, J; Denavit-Saubié, M

    1996-01-01

    neurons located in the rostral ventrolateral part of the slice. 2. Bath-applied TRH (1 microM) decreased the time between inspiratory discharges recorded on the XII nerve from 12.3 +/- 3.3 s to 4.9 +/- 1.1 s (n = 28; means +/- SD), i.e., caused an approximate threefold increase in the respiratory...... frequency. The coefficient of variation of the time between the inspiratory discharges decreased by one-half. Thus the respiratory output became more stable in response to TRH. The duration of the inspiratory discharges increased from 474 +/- 108 ms to 679 +/- 114 ms, and the amplitude decreased by 24...... in a thick brain stem slice preparation from the newborn mouse. The action of TRH on the respiratory output from the slice was investigated by recordings from the XII nerve. Cellular responses to TRH were investigated using whole cell recordings from hypoglossal motoneurons and three types of inspiratory...

  18. Large-scale automated image analysis for computational profiling of brain tissue surrounding implanted neuroprosthetic devices using Python.

    Science.gov (United States)

    Rey-Villamizar, Nicolas; Somasundar, Vinay; Megjhani, Murad; Xu, Yan; Lu, Yanbin; Padmanabhan, Raghav; Trett, Kristen; Shain, William; Roysam, Badri

    2014-01-01

    In this article, we describe the use of Python for large-scale automated server-based bio-image analysis in FARSIGHT, a free and open-source toolkit of image analysis methods for quantitative studies of complex and dynamic tissue microenvironments imaged by modern optical microscopes, including confocal, multi-spectral, multi-photon, and time-lapse systems. The core FARSIGHT modules for image segmentation, feature extraction, tracking, and machine learning are written in C++, leveraging widely used libraries including ITK, VTK, Boost, and Qt. For solving complex image analysis tasks, these modules must be combined into scripts using Python. As a concrete example, we consider the problem of analyzing 3-D multi-spectral images of brain tissue surrounding implanted neuroprosthetic devices, acquired using high-throughput multi-spectral spinning disk step-and-repeat confocal microscopy. The resulting images typically contain 5 fluorescent channels. Each channel consists of 6000 × 10,000 × 500 voxels with 16 bits/voxel, implying image sizes exceeding 250 GB. These images must be mosaicked, pre-processed to overcome imaging artifacts, and segmented to enable cellular-scale feature extraction. The features are used to identify cell types, and perform large-scale analysis for identifying spatial distributions of specific cell types relative to the device. Python was used to build a server-based script (Dell 910 PowerEdge servers with 4 sockets/server with 10 cores each, 2 threads per core and 1TB of RAM running on Red Hat Enterprise Linux linked to a RAID 5 SAN) capable of routinely handling image datasets at this scale and performing all these processing steps in a collaborative multi-user multi-platform environment. Our Python script enables efficient data storage and movement between computers and storage servers, logs all the processing steps, and performs full multi-threaded execution of all codes, including open and closed-source third party libraries.

  19. Large-scale automated image analysis for computational profiling of brain tissue surrounding implanted neuroprosthetic devices using Python

    Directory of Open Access Journals (Sweden)

    Nicolas eRey-Villamizar

    2014-04-01

    Full Text Available In this article, we describe use of Python for large-scale automated server-based bio-image analysis in FARSIGHT, a free and open-source toolkit of image analysis methods for quantitative studies of complex and dynamic tissue microenvironments imaged by modern optical microscopes including confocal, multi-spectral, multi-photon, and time-lapse systems. The core FARSIGHT modules for image segmentation, feature extraction, tracking, and machine learning are written in C++, leveraging widely used libraries including ITK, VTK, Boost, and Qt. For solving complex image analysis task, these modules must be combined into scripts using Python. As a concrete example, we consider the problem of analyzing 3-D multi-spectral brain tissue images surrounding implanted neuroprosthetic devices, acquired using high-throughput multi-spectral spinning disk step-and-repeat confocal microscopy. The resulting images typically contain 5 fluorescent channels, 6,000$times$10,000$times$500 voxels with 16 bits/voxel, implying image sizes exceeding 250GB. These images must be mosaicked, pre-processed to overcome imaging artifacts, and segmented to enable cellular-scale feature extraction. The features are used to identify cell types, and perform large-scale analytics for identifying spatial distributions of specific cell types relative to the device. Python was used to build a server-based script (Dell 910 PowerEdge servers with 4 sockets/server with 10 cores each, 2 threads per core and 1TB of RAM running on Red Hat Enterprise Linux linked to a RAID 5 SAN capable of routinely handling image datasets at this scale and performing all these processing steps in a collaborative multi-user multi-platform environment consisting. Our Python script enables efficient data storage and movement between compute and storage servers, logging all processing steps, and performs full multi-threaded execution of all codes, including open and closed-source third party libraries.

  20. Development and Characterization of a Brain Endothelial Cell Phenotype using Human Induced Pluripotent Stem Cells

    DEFF Research Database (Denmark)

    Goldeman, Charlotte; Saaby, Lasse; Holst, Bjørn

    for experiments the following day. The model was monitored by measuring the trans-endothelial electrical resistance (TEER). RA had an inductive effect on the model, shown by an elevation in barrier tightness which correlated with the presence of tight junction proteins, shown by confocal microscopy images which...... be used to investigate drug transport in vitro, and screen candidates for permeation properties. One recent approach is to develop in vitro models of the BBB using human induced pluripotent stem cells (hIPSCs) as described by Stebbins et al. (2015).The aim of the present study was to investigate whether...... the published protocols were generically applicable and thus to develop and characterize in vitro models of the BBB using hIPSCs from different sources. Two stem cell lines, Bioni010-C and WTSli024-A, were seeded and maintained on Matrigel in mTesR1 media. Cells were then seeded as single cells at different...

  1. Quiescent Oct4+ Neural Stem Cells (NSCs) Repopulate Ablated Glial Fibrillary Acidic Protein+ NSCs in the Adult Mouse Brain.

    Science.gov (United States)

    Reeve, Rachel L; Yammine, Samantha Z; Morshead, Cindi M; van der Kooy, Derek

    2017-09-01

    Adult primitive neural stem cells (pNSCs) are a rare population of glial fibrillary acidic protein (GFAP) - Oct4 + cells in the mouse forebrain subependymal zone bordering the lateral ventricles that give rise to clonal neurospheres in leukemia inhibitory factor in vitro. pNSC neurospheres can be passaged to self-renew or give rise to GFAP + NSCs that form neurospheres in epidermal growth factor and fibroblast growth factor 2, which we collectively refer to as definitive NSCs (dNSCs). Label retention experiments using doxycycline-inducible histone-2B (H2B)-green fluorescent protein (GFP) mice and several chase periods of up to 1 year quantified the adult pNSC cell cycle time as 3-5 months. We hypothesized that while pNSCs are not very proliferative at baseline, they may exist as a reserve pool of NSCs in case of injury. To test this function of pNSCs, we obtained conditional Oct4 knockout mice, Oct4 fl/fl ;Sox1 Cre (Oct4 CKO ), which do not yield adult pNSC-derived neurospheres. When we ablated the progeny of pNSCs, namely all GFAP + dNSCs, in these Oct4 CKO mice, we found that dNSCs did not recover as they do in wild-type mice, suggesting that pNSCs are necessary for dNSC repopulation. Returning to the H2B-GFP mice, we observed that the cytosine β-d-arabinofuranoside ablation of proliferating cells including dNSCs-induced quiescent pNSCs to proliferate and significantly dilute their H2B-GFP label. In conclusion, we demonstrate that pNSCs are the most quiescent stem cells in the adult brain reported to date and that their lineage position upstream of GFAP + dNSCs allows them to repopulate a depleted neural lineage. Stem Cells 2017;35:2071-2082. © 2017 AlphaMed Press.

  2. MR tracking of stem cells labeled with superparamagnetic nanoparticles in ischemic brain

    Czech Academy of Sciences Publication Activity Database

    Jendelová, Pavla; Růžičková, Kateřina; Urdzíková, Lucia; Kroupová, Jana; Herynek, V.; Dvořák, Petr; Hájek, M.; Syková, Eva

    č. 2 (2003), s. 35 ISSN 0894-1491. [European Meeting on Glia l Cell Function in Health and Disease /6./. Berlín, 03.09.2003-06.09.2003] R&D Projects: GA MŠk LN00A065; GA ČR GA304/03/1189 Institutional research plan: CEZ:AV0Z5039906; CEZ:MSM 111300004 Keywords : Stem cells * Nanoparticles Subject RIV: FH - Neurology Impact factor: 4.677, year: 2003

  3. Geminin Participates in Differentiation Decisions of Adult Neural Stem Cells Transplanted in the Hemiparkinsonian Mouse Brain.

    Science.gov (United States)

    Taouki, Ioanna; Tasiudi, Eve; Lalioti, Maria-Eleni; Kyrousi, Christina; Skavatsou, Eleni; Kaplani, Konstantina; Lygerou, Zoi; Kouvelas, Elias D; Mitsacos, Adamantia; Giompres, Panagiotis; Taraviras, Stavros

    2017-08-15

    Neural stem cells have been considered as a source of stem cells that can be used for cell replacement therapies in neurodegenerative diseases, as they can be isolated and expanded in vitro and can be used for autologous grafting. However, due to low percentages of survival and varying patterns of differentiation, strategies that will enhance the efficacy of transplantation are under scrutiny. In this article, we have examined whether alterations in Geminin's expression, a protein that coordinates the balance between self-renewal and differentiation, can improve the properties of stem cells transplanted in 6-OHDA hemiparkinsonian mouse model. Our results indicate that, in the absence of Geminin, grafted cells differentiating into dopaminergic neurons were decreased, while an increased number of oligodendrocytes were detected. The number of proliferating multipotent cells was not modified by the absence of Geminin. These findings encourage research related to the impact of Geminin on transplantations for neurodegenerative disorders, as an important molecule in influencing differentiation decisions of the cells composing the graft.

  4. 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...

  5. In-vitro interactions of human chondrocytes and mesenchymal stem cells, and of mouse macrophages with phospholipid-covered metallic implant materials

    Directory of Open Access Journals (Sweden)

    R Willumeit

    2007-03-01

    Full Text Available Phospholipid-coatings on metallic implant surfaces were evaluated in terms of adhesion, proliferation and matrix production of skeletal cells, and of macrophage stimulation. The working hypothesis is that mimicking a model biomembrane by phospholipids on surfaces to which cells adhere, the surface recognition by surrounding cells is altered. In this study, 1 mirror-like polished Ti-6Al-7Nb and 2 porous Ti-6Al-4V specimens were covered with the phospholipids POPE (palmitoyl-oleoyl phosphatidyl-ethanolamine and POPC (palmitoyl-oleoyl phosphatidyl-choline, and the interactions of a human articular chondrocytes (HAC, b human mesenchymal stem cells (HMSC, and c mouse macrophages (RAW 264.7 were tested in vitro. On POPE-covered polished surfaces adherence of HAC (42% of seeded cells after 2 hrs and metabolic activity (MTT after 3 days were reduced, while on porous surfaces 99% HAC adhered, and metabolic activity was significantly increased, compared to respective native surfaces. On both POPE-covered surfaces the chondrocyte phenotype was present. After 3 weeks of chondrogenic differentiation, cartilage matrix production (measuring chondroitin sulphate per HAC number was significantly increased by about 30% on both POPE-covered metallic surfaces. On both POPC-covered surfaces nearly no adhering and surviving HAC were found. HMSC grown on POPE-covered porous substrates showed osteogenic differentiation by improved osteopontin and collagen I expression in RT-PCR, and osteocalcin fluorescence and bone nodule formation was only detectable on POPE-covered porous surfaces. In contrast to POPC and other phospholipids used as positive controls, POPE did not stimulate the NO production in mouse macrophage cultures. We therefore conclude that a phospholipid coating by POPE shows potential as surface modification for metallic implant materials.

  6. Controlling micro- and nano-environment of tumor and stem cells for novel research and therapy of brain cancer

    Science.gov (United States)

    Smith, Christopher Lloyd

    The use of modern technologies in cancer research has engendered a great deal of excitement. Many of these advanced approaches involve in-depth mathematical analyses of the inner working of cells, via genomic and proteomic analyses. However these techniques may not be ideal for the study of complex cell phenotypes and behaviors. This dissertation explores cancer and potential therapies through phenotypic analysis of cell behaviors, an alternative approach. We employ this experimental framework to study brain cancer (glioma), a particularly formidable example of this diverse ailment. Through the application of micro- and nanotechnology, we carefully control the surrounding environments of cells to understand their responses to various cues and to manipulate their behaviors. Subsequently we obtain clinically relevant information that allows better understanding of glioma, and enhancement of potential therapies. We first aim to address brain tumor dispersal, through analysis of cell migration. Utilizing nanometer-scale topographic models of the extracellular matrix, we study the migratory response of glioma cells to various stimuli in vitro. Second, we implement knowledge gained from these investigations to define characteristics of tumor progression in patients, and to develop treatments inhibiting cell migration. Next we use microfluidic and nanotopographic models to study the behaviors of stem cells in vitro. Here we attempt to improve their abilities to deliver therapeutic proteins to cancer, an innovative treatment approach. We analyze the multi-step process by which adipose-derived stem cells naturally home to tumor sites, and identify numerous environmental perturbations to enhance this behavior. Finally, we attempt to demonstrate that these cell culture-based manipulations can enhance the localization of adipose stem cells to glioma in vivo using animal models. Throughout this work we utilize environmental cues to analyze and induce particular behaviors in

  7. 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.

  8. Astroglial Activation by an Enriched Environment after Transplantation of Mesenchymal Stem Cells Enhances Angiogenesis after Hypoxic-Ischemic Brain Injury

    Directory of Open Access Journals (Sweden)

    Sung-Rae Cho

    2016-09-01

    Full Text Available Transplantation of mesenchymal stem cells (MSCs has paracrine effects; however, the effects are known to be largely limited. Here we investigated the combination effects of cell transplantation and enriched environment (EE in a model of hypoxic-ischemic brain injury. Brain damage was induced in seven-day-old mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2 for 90 min. At six weeks of age, the mice were randomly assigned to four groups: phosphate-buffered saline (PBS-control (CON, PBS-EE, MSC-CON, and MSC-EE. Rotarod and grip strength tests were performed to evaluate neurobehavioral functions. Histologic evaluations were also performed to confirm the extent of astrocyte activation and endogenous angiogenesis. An array-based multiplex ELISA and Western blot were used to identify growth factors in vivo and in vitro. Two weeks after treatment, levels of astrocyte density and angiogenic factors were increased in MSC-EE mice, but glial scarring was not increased. Eight weeks after treatment, angiogenesis was increased, and behavioral outcomes were synergistically improved in the MSC-EE group. Astrocytes co-cultured with MSCs expressed higher levels of angiogenic factors than astrocytes cultured alone. The mechanisms of this synergistic effect included enhanced repair processes, such as increased endogenous angiogenesis and upregulation of angiogenic factors released from activated astrocytes.

  9. Cerebral transplantation of encapsulated mesenchymal stem cells improves cellular pathology after experimental traumatic brain injury

    DEFF Research Database (Denmark)

    Heile, Anna M B; Wallrapp, Christine; Klinge, Petra M

    2009-01-01

    -protective substance glucagon-like peptide-1 (GLP-1). METHODS: Thirty two Sprague-Dawley rats were randomized to five groups: controls (no CCI), CCI-only, CCI+eMSC, CCI+GLP-1 eMSC, and CCI+empty capsules. On day 14, cisternal cerebro-spinal fluid (CSF) was sampled for measurement of GLP-1 concentration. Brains were...

  10. Repair of neonatal brain injury : bringing stem cell-based therapy into clinical practice

    NARCIS (Netherlands)

    Wagenaar, Nienke; Nijboer, Cora H.; van Bel, Frank

    2017-01-01

    Hypoxic-ischaemic brain injury is one of most important causes of neonatal mortality and long-term neurological morbidity in infants born at term. At present, only hypothermia in infants with perinatal hypoxic-ischaemic encephalopathy has shown benefit as a neuroprotective strategy. Otherwise,

  11. Cortical and brain stem changes in neural activity during static handgrip and postexercise ischemia in humans

    DEFF Research Database (Denmark)

    Sander, Mikael; Macefield, Vaughan G; Henderson, Luke A

    2010-01-01

    , and to differentiate between central command and reflex inputs, we used blood oxygen level-dependent (BOLD) functional MRI (fMRI) of the whole brain (3 T). Subjects performed submaximal static handgrip exercise for 2 min followed by 6 min of PEI; MSNA was recorded on a separate day. During the contraction phase...

  12. Hypoxia-Mediated Epigenetic Regulation of Stemness in Brain Tumor Cells.

    Science.gov (United States)

    Prasad, Pankaj; Mittal, Shivani Arora; Chongtham, Jonita; Mohanty, Sujata; Srivastava, Tapasya

    2017-06-01

    Activation of pluripotency regulatory circuit is an important event in solid tumor progression and the hypoxic microenvironment is known to enhance the stemness feature of some cells. The distinct population of cancer stem cells (CSCs)/tumor initiating cells exist in a niche and augment invasion, metastasis, and drug resistance. Previously, studies have reported global hypomethylation and site-specific aberrant methylation in gliomas along with other epigenetic modifications as important contributors to genomic instability during glioma progression. Here, we have demonstrated the role of hypoxia-mediated epigenetic modifications in regulating expression of core pluripotency factors, OCT4 and NANOG, in glioma cells. We observe hypoxia-mediated induction of demethylases, ten-eleven-translocation (TET) 1 and 3, but not TET2 in our cell-line model. Immunoprecipitation studies reveal active demethylation and direct binding of TET1 and 3 at the Oct4 and Nanog regulatory regions. Tet1 and 3 silencing assays further confirmed induction of the pluripotency pathway involving Oct4, Nanog, and Stat3, by these paralogues, although with varying degrees. Knockdown of Tet1 and Tet3 inhibited the formation of neurospheres in hypoxic conditions. We observed independent roles of TET1 and TET3 in differentially regulating pluripotency and differentiation associated genes in hypoxia. Overall, this study demonstrates an active demethylation in hypoxia by TET1 and 3 as a mechanism of Oct4 and Nanog overexpression thus contributing to the formation of CSCs in gliomas. Stem Cells 2017;35:1468-1478. © 2017 AlphaMed Press.

  13. Phenotypic and gene expression modification with normal brain aging in GFAP-positive astrocytes and neural stem cells.

    Science.gov (United States)

    Bernal, Giovanna M; Peterson, Daniel A

    2011-06-01

    Astrocytes secrete growth factors that are both neuroprotective and supportive for the local environment. Identified by glial fibrillary acidic protein (GFAP) expression, astrocytes exhibit heterogeneity in morphology and in the expression of phenotypic markers and growth factors throughout different adult brain regions. In adult neurogenic niches, astrocytes secrete vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) within the neurogenic niche and are also a source of special GFAP-positive multipotent neural stem cells (NSCs). Normal aging is accompanied by a decline in CNS function and reduced neurogenesis. We asked whether a decreased availability of astrocyte-derived factors may contribute to the age-related decline in neurogenesis. Determining alterations of astrocytic activity in the aging brain is crucial for understanding CNS homeostasis in aging and for assessing appropriate therapeutic targets for an aging population. We found region-specific alterations in the gene expression of GFAP, VEGF, and FGF-2 and their receptors in the aged brain corresponding to changes in astrocytic reactivity, supporting astrocytic heterogeneity and demonstrating a differential aging effect. We found that GFAP-positive NSCs uniquely coexpress both VEGF and its key mitotic receptor Flk-1 in both young and aged hippocampus, indicating a possible autocrine/paracrine signaling mechanism. VEGF expression is lost once NSCs commit to a neuronal fate, but Flk-1-mediated sensitivity to VEGF signaling is maintained. We propose that age-related astrocytic changes result in reduced VEGF and FGF-2 signaling, which in turn limits NSC and progenitor cell maintenance and contributes to decreased neurogenesis. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

  14. Effect of all-trans retinoic acid on the proliferation and differentiation of brain tumor stem cells

    Directory of Open Access Journals (Sweden)

    Niu Chao

    2010-08-01

    Full Text Available Abstract Objective To investigate the effect of all-trans retinoic acid(ATRA on the proliferation and differentiation of brain tumor stem cells(BTSCs in vitro. Methods Limiting dilution and clonogenic assay were used to isolate and screen BTSCs from the fresh specimen of human brain glioblastoma. The obtained BTSCs, which were cultured in serum-free medium, were classified into four groups in accordance with the composition of the different treatments. The proliferation of the BTSCs was evaluated by MTT assay. The BTSCs were induced to differentiate in serum-containing medium, and classified into the ATRA group and control group. On the 10th day of induction, the expressions of CD133 and glial fibrillary acidic protein (GFAP in the differentiated BTSCs were detected by immunofluorescence. The differentiated BTSCs were cultured in serum-free medium, the percentage and the time required for formation of brain tumor spheres (BTS were observed. Results BTSCs obtained by limiting dilution were all identified as CD133-positive by immunofluorescence. In serum-free medium, the proliferation of BTSCs in the ATRA group was observed significantly faster than that in the control group, but slower than that in the growth factor group and ATRA/growth factor group, and the size of the BTS in the ATRA group was smaller than that in the latter two groups(P P P P Conclusion ATRA can promote the proliferation and induce the differentiation of BTSCs, but the differentiation is incomplete, terminal differentiation cannot be achieved and BTSs can be formed again.

  15. 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)

  16. Diagnostic challenges in primary brain stem glioblastoma multiform; a case report

    Directory of Open Access Journals (Sweden)

    Muhammad Taimur Malik, MD

    2017-12-01

    Full Text Available Brainstem gliomas are rare form of primary brain tumors in adult and represent <2% of gliomas. Glioblastomas (GBM are much less common in pediatric patients; adult GBM vary in presentation and response to therapy, and generally have a very poor prognosis. GBM is less common in the brainstem, comprising <2% gliomas and there is therefore limited data available to provide a standard of care. Here we present a case report of a patient who presented with aggressive primary pontine GBM.

  17. Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury.

    Science.gov (United States)

    Donega, Vanessa; Nijboer, Cora H; van Tilborg, Geralda; Dijkhuizen, Rick M; Kavelaars, Annemieke; Heijnen, Cobi J

    2014-11-01

    Previous work from our group has shown that intranasal MSC-treatment decreases lesion volume and improves motor and cognitive behavior after hypoxic-ischemic (HI) brain damage in neonatal mice. Our aim was to determine the kinetics of MSC migration after intranasal administration, and the early effects of MSCs on neurogenic processes and gliosis at the lesion site. HI brain injury was induced in 9-day-old mice and MSCs were administered intranasally at 10days post-HI. The kinetics of MSC migration were investigated by immunofluorescence and MRI analysis. BDNF and NGF gene expression was determined by qPCR analysis following MSC co-culture with HI brain extract. Nestin, Doublecortin, NeuN, GFAP, Iba-1 and M1/M2 phenotypic expression was assessed over time. MRI and immunohistochemistry analyses showed that MSCs reach the lesion site already within 2h after intranasal administration. At 12h after administration the number of MSCs at the lesion site peaks and decreases significantly at 72h. The number of DCX(+) cells increased 1 to 3days after MSC administration in the SVZ. At the lesion, GFAP(+)/nestin(+) and DCX(+) expression increased 3 to 5days after MSC-treatment. The number of NeuN(+) cells increased within 5days, leading to a dramatic regeneration of the somatosensory cortex and hippocampus at 18days after intranasal MSC administration. Interestingly, MSCs expressed significantly more BDNF gene when exposed to HI brain extract in vitro. Furthermore, MSC-treatment resulted in the resolution of the glial scar surrounding the lesion, represented by a decrease in reactive astrocytes and microglia and polarization of microglia towards the M2 phenotype. In view of the current lack of therapeutic strategies, we propose that intranasal MSC administration is a powerful therapeutic option through its functional repair of the lesion represented by regeneration of the cortical and hippocampal structure and decrease of gliosis. Copyright © 2014. Published by Elsevier Inc.

  18. Combination of systemic chemotherapy with local stem cell delivered S-TRAIL in resected brain tumors.

    Science.gov (United States)

    Redjal, Navid; Zhu, Yanni; Shah, Khalid

    2015-01-01

    Despite advances in standard therapies, the survival of glioblastoma multiforme (GBM) patients has not improved. Limitations to successful translation of new therapies include poor delivery of systemic therapies and use of simplified preclinical models which fail to reflect the clinical complexity of GBMs. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis specifically in tumor cells and we have tested its efficacy by on-site delivery via engineered stem cells (SC) in mouse models of GBM that mimic the clinical scenario of tumor aggressiveness and resection. However, about half of tumor lines are resistant to TRAIL and overcoming TRAIL-resistance in GBM by combining therapeutic agents that are currently in clinical trials with SC-TRAIL and understanding the molecular dynamics of these combination therapies are critical to the broad use of TRAIL as a therapeutic agent in clinics. In this study, we screened clinically relevant chemotherapeutic agents for their ability to sensitize resistant GBM cell lines to TRAIL induced apoptosis. We show that low dose cisplatin increases surface receptor expression of death receptor 4/5 post G2 cycle arrest and sensitizes GBM cells to TRAIL induced apoptosis. In vivo, using an intracranial resection model of resistant primary human-derived GBM and real-time optical imaging, we show that a low dose of cisplatin in combination with synthetic extracellular matrix encapsulated SC-TRAIL significantly decreases tumor regrowth and increases survival in mice bearing GBM. This study has the potential to help expedite effective translation of local stem cell-based delivery of TRAIL into the clinical setting to target a broad spectrum of GBMs. © 2014 AlphaMed Press.

  19. Intermittent Hypoxia and Stem Cell Implants Preserve Breathing Capacity in a Rodent Model of Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Nichols, Nicole L.; Gowing, Genevieve; Satriotomo, Irawan; Nashold, Lisa J.; Dale, Erica A.; Suzuki, Masatoshi; Avalos, Pablo; Mulcrone, Patrick L.; McHugh, Jacalyn

    2013-01-01

    Rationale: Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease causing paralysis and death from respiratory failure. Strategies to preserve and/or restore respiratory function are critical for successful treatment. Although breathing capacity is maintained until late in disease progression in rodent models of familial ALS (SOD1G93A rats and mice), reduced numbers of phrenic motor neurons and decreased phrenic nerve activity are observed. Decreased phrenic motor output suggests imminent respiratory failure. Objectives: To preserve or restore phrenic nerve activity in SOD1G93A rats at disease end stage. Methods: SOD1G93A rats were injected with human neural progenitor cells (hNPCs) bracketing the phrenic motor nucleus before disease onset, or exposed to acute intermittent hypoxia (AIH) at disease end stage. Measurements and Main Results: The capacity to generate phrenic motor output in anesthetized rats at disease end stage was: (1) transiently restored by a single presentation of AIH; and (2) preserved ipsilateral to hNPC transplants made before disease onset. hNPC transplants improved ipsilateral phrenic motor neuron survival. Conclusions: AIH-induced respiratory plasticity and stem cell therapy have complementary translational potential to treat breathing deficits in patients with ALS. PMID:23220913

  20. 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.

  1. 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)

  2. Hypoxic-preconditioning enhances the regenerative capacity of neural stem/progenitors in subventricular zone of newborn piglet brain.

    Science.gov (United States)

    Ara, Jahan; De Montpellier, Sybille

    2013-09-01

    Perinatal hypoxia-ischemia (HI) results in brain injury, whereas mild hypoxic episodes result in preconditioning, which can significantly reduce the vulnerability of the brain to subsequent severe hypoxia-ischemia. Hypoxic-preconditioning (PC) has been shown to enhance cell survival and differentiation of progenitor cells in the central nervous system (CNS). The purpose of this study was to determine whether pretreatment with PC prior to HI stimulates subventricular zone (SVZ) proliferation and neurogenesis in newborn piglets. One-day-old piglets were subjected to PC (8% O2/92% N2) for 3h and 24h later were exposed to HI produced by combination of hypoxia (5% FiO2) for a pre-defined period of 30min and ischemia induced by a period of 10min of hypotension. Here we demonstrate that SVZ derived neural stem/progenitor cells (NSPs) from PC, HI and PC+HI piglets proliferated as neurospheres, expressed neural progenitor and neurodevelopmental markers, and that greater proportion of the spheres generated are multipotential. Neurosphere assay revealed that preconditioning pretreatment increased the number of NSP-derived neurospheres in SVZ following HI compared to normoxic and HI controls. NSPs from preconditioned SVZ generated twice as many neurons and astrocytes in vitro. Injections with 5-Bromo-2-deoxyuridine (BrdU) after PC revealed a robust proliferative response within the SVZ that continued for one week. PC also increased neurogenesis in vivo, doublecortin positive cells with migratory profiles were observed streaming from the SVZ to striatum and neocortex. These findings show that the induction of proliferation and neurogenesis by PC might be a positive adaptation for an efficient repair and plasticity in the event of a hypoxic-ischemic insult. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. 14C-dopamine microinjected into the brain-stem of the rat: dispersion kinetics, site content and functional dose

    International Nuclear Information System (INIS)

    Myers, R.D.; Hoch, D.B.

    1978-01-01

    A morphological analysis was undertaken of both the dispersion characteristics and tissue content of dopamine (DA) microinjected acutely into the brain-stem of the anesthetized rat. 14C-DA, with a specific activity of 56-62 mCi/mMol, was infused unilaterally into the pars compacta of the substantia nigra in one of four test volumes: 0.5, 1.0, 4.0 or 8.0 microliters. The concentration of the 14C-DA solution was 1.0 microCi/microliter, equivalent to 3.01 micrograms/microliters, which was delivered at an injection rate of 1.0 microliter per 45 sec. At an interval of either one min or 15 min following the microinjection, the rat's brain was removed rapidly from its calvarium, flash frozen and then cut in the coronal plane on a freezing microtome in 500 micron slabs. After each of the respective serial slabs was mounted on glass, the Eik Nes-Brizzee trochar technique for the discrete removal of tissue samples was used to obtain 0.5 mm dia. cylindrical plugs of meso-diencephalic tissue at distances from the site of injection ranging from 0.5 to 2.5 mm, center to center. Each sample plug was subsequently solubilized and 14C-DA activity quantitated by liquid scintillation spectrometry. The results show that regardless of volume, the spatial patterning of the microinjected solution assumes a tear-drop or pear shape, not a sphere. Further, as the volume of the injection is increased from 0.5 to 8.0 microliters, the magnitude of the dispersion of 14C-DA is enhanced throughout the surrounding parenchyma, but not in a linear fashion

  4. Implantation of glioblastoma spheroids into organotypic brain slice cultures as a model for investigating effects of irradiation

    DEFF Research Database (Denmark)

    Petterson, Stine Asferg; Jakobsen, Ida Pind; Jensen, Stine Skov

    2016-01-01

    , models for studying the effects of radiotherapy in combination with novel strategies are lacking but important since radiotherapy is the most successful non-surgical treatment of brain tumors. The aim of this study was to establish a glioblastoma spheroid-organotypic rat brain slice culture model...... comprising both tumors, tumor-brain interface and brain tissue to provide a proof of concept that this model is useful for studying effects of radiotherapy. Organotypic brain slice cultures cultured for 1-2 days or 11-16 days corresponding to immature brain and mature brain respectively were irradiated...... with doses between 10 and 50 Gy. There was a high uptake of the cell death marker propidium iodide in the immature cultures. In addition, MAP2 expression decreased whereas GFAP expression increased in these cultures suggesting neuronal death and astrogliosis. We therefore proceeded with the mature cultures...

  5. 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.)

  6. 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...

  7. 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.)

  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. Evaluation of intervertebral disc regeneration with implantation of bone marrow mesenchymal stem cells (BMSCs) using quantitative T2 mapping: a study in rabbits.

    Science.gov (United States)

    Cai, Feng; Wu, Xiao-Tao; Xie, Xin-Hui; Wang, Feng; Hong, Xin; Zhuang, Su-Yang; Zhu, Lei; Rui, Yun-Feng; Shi, Rui

    2015-01-01

    The aim of the study was to investigate the curative effects of transplantation of bone marrow mesenchymal stem cells (BMSCs) on intervertebral disc regeneration and to investigate the feasibility of the quantitative T2 mapping method for evaluating repair of the nucleus pulposus after implantation of BMSCs. Forty-eight New Zealand white rabbits were used to establish the lumber disc degenerative model by stabbing the annulus fibrosus and then randomly divided into four groups, i.e. two weeks afterwards, BMSCs or phosphate-buffered saline (PBS) were transplanted into degenerative discs (BMSCs group and PBS group), while the operated rabbits without implantation of BMSCs or PBS served as the sham group and the rabbits without operation were used as the control group. At weeks two, six and ten after operation, the T2 values and disc height indices (DHI) were calculated by magnetic resonance imaging (MRI 3.0 T), and the gene expressions of type II collagen (COL2) and aggrecan (ACAN) in degenerative discs were evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR). T2 values for the nucleus pulposus were correlated with ACAN or COL2 expression by regression analysis. Cell clusters, disorganised fibres, interlamellar glycosaminoglycan (GAG) matrix and vascularisation were observed in lumber degenerative discs. BMSCs could be found to survive in intervertebral discs and differentiate into nucleus pulposus-like cells expressing COL2 and ACAN. The gene expression of COL2 and ACAN increased during ten weeks after transplantation as well as the T2 signal intensity and T2 value. The DHI in the BMSCs group decreased more slowly than that in PBS and sham groups. The T2 value correlated significantly with the gene expression of ACAN and COL2 in the nucleus pulposus. Transplantation of BMSCs was able to promote the regeneration of degenerative discs. Quantitative and non-invasive T2 mapping could be used to evaluate the regeneration of the nucleus

  10. 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.

  11. 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.

  12. 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.

  13. Neuronal coupling by endogenous electric fields: cable theory and applications to coincidence detector neurons in the auditory brain stem.

    Science.gov (United States)

    Goldwyn, Joshua H; Rinzel, John

    2016-04-01

    The ongoing activity of neurons generates a spatially and time-varying field of extracellular voltage (Ve). This Ve field reflects population-level neural activity, but does it modulate neural dynamics and the function of neural circuits? We provide a cable theory framework to study how a bundle of model neurons generates Ve and how this Ve feeds back and influences membrane potential (Vm). We find that these "ephaptic interactions" are small but not negligible. The model neural population can generate Ve with millivolt-scale amplitude, and this Ve perturbs the Vm of "nearby" cables and effectively increases their electrotonic length. After using passive cable theory to systematically study ephaptic coupling, we explore a test case: the medial superior olive (MSO) in the auditory brain stem. The MSO is a possible locus of ephaptic interactions: sounds evoke large (millivolt scale)Vein vivo in this nucleus. The Ve response is thought to be generated by MSO neurons that perform a known neuronal computation with submillisecond temporal precision (coincidence detection to encode sound source location). Using a biophysically based model of MSO neurons, we find millivolt-scale ephaptic interactions consistent with the passive cable theory results. These subtle membrane potential perturbations induce changes in spike initiation threshold, spike time synchrony, and time difference sensitivity. These results suggest that ephaptic coupling may influence MSO function. Copyright © 2016 the American Physiological Society.

  14. Over-expression of brain-derived neurotrophic factor in mesenchymal stem cells transfected with recombinant lentivirus BDNF gene.

    Science.gov (United States)

    Zhang, X; Zhu, J; Zhang, K; Liu, T; Zhang, Z

    2016-12-30

    This study was aimed at investigating the expression of brain-derived neurotrophic factor (BDNF) in mesenchymal stem cells (MSCs) modified with recombinant lentivirus bearing BDNF gene. Lentivirus vectors bearing BDNF gene were constructed. MSCs were isolated from rats and cultured. The lentiviral vectors containing BDNF gene were transfected into the MSCs, and BDNF gene and protein expressions were monitored with enhanced green fluorescent protein (EGFP). RT-PCR and Western blot were used to measure gene and protein expressions, respectibvely in MSCs, MSCs-EGFP and MSCs-EGFP-BDNF groups. Green fluorescence assay confirmed successful transfection of BDNF gene recombinant lentivirus into MSCs. RT-PCR and Western blot revealed that BDNF gene and protein expressions in the MSCs-EGFP-BDNF group were significantly higher than that in MSCs group and MSCs-EGFP group. There were no statistically significant differences in gene expression between MSCs and MSCs-EGFP groups. MSCs can over-express BDNF when transfected with recombinant lentivirus bearing BDNF gene.

  15. Effect of controlled release of brain-derived neurotrophic factor and neurotrophin-3 from collagen gel on neural stem cells.

    Science.gov (United States)

    Huang, Fei; Wu, Yunfeng; Wang, Hao; Chang, Jun; Ma, Guangwen; Yin, Zongsheng

    2016-01-20

    This study aimed to examine the effect of controlled release of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) from collagen gel on rat neural stem cells (NSCs). With three groups of collagen gel, BDNF/collagen gel, and NT-3/collagen gel as controls, BDNF and NT-3 were tested in the BDNF-NT-3/collagen gel group at different time points. The enzyme-linked immunosorbent assay results showed that BDNF and NT-3 were steadily released from collagen gels for 10 days. The cell viability test and the bromodeoxyuridine incorporation assay showed that BDNF-NT-3/collagen gel supported the survival and proliferation of NSCs. The results also showed that the length of processes was markedly longer and differentiation percentage from NSCs into neurons was much higher in the BDNF-NT-3/collagen gel group than those in the collagen gel, BDNF/collagen gel, and NT-3/collagen gel groups. These findings suggest that BDNF-NT-3/collagen gel could significantly improve the ability of NSCs proliferation and differentiation.

  16. Transplanted Adult Neural Stem Cells Express Sonic Hedgehog In Vivo and Suppress White Matter Neuroinflammation after Experimental Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Genevieve M. Sullivan

    2017-01-01

    Full Text Available Neural stem cells (NSCs delivered intraventricularly may be therapeutic for diffuse white matter pathology after traumatic brain injury (TBI. To test this concept, NSCs isolated from adult mouse subventricular zone (SVZ were transplanted into the lateral ventricle of adult mice at two weeks post-TBI followed by analysis at four weeks post-TBI. We examined sonic hedgehog (Shh signaling as a candidate mechanism by which transplanted NSCs may regulate neuroregeneration and/or neuroinflammation responses of endogenous cells. Mouse fluorescent reporter lines were generated to enable in vivo genetic labeling of cells actively transcribing Shh or Gli1 after transplantation and/or TBI. Gli1 transcription is an effective readout for canonical Shh signaling. In ShhCreERT2;R26tdTomato mice, Shh was primarily expressed in neurons and was not upregulated in reactive astrocytes or microglia after TBI. Corroborating results in Gli1CreERT2;R26tdTomato mice demonstrated that Shh signaling was not upregulated in the corpus callosum, even after TBI or NSC transplantation. Transplanted NSCs expressed Shh in vivo but did not increase Gli1 labeling of host SVZ cells. Importantly, NSC transplantation significantly reduced reactive astrogliosis and microglial/macrophage activation in the corpus callosum after TBI. Therefore, intraventricular NSC transplantation after TBI significantly attenuated neuroinflammation, but did not activate host Shh signaling via Gli1 transcription.

  17. Activation of PAF-synthesizing enzymes in rat brain stem slices after LTP induction in the medial vestibular nuclei.

    Science.gov (United States)

    Francescangeli, Ermelinda; Grassi, Silvarosa; Pettorossi, Vito E; Goracci, Gianfrancesco

    2002-11-01

    LysoPAF acetyltransferase (lysoPAF-AT) and PAF-synthesizing phosphocholinetransferase (PAF-PCT) are the two enzymes which catalyze the final reactions for the synthesis of PAF. Their activities, assayed in the homogenate of rat brain stem slices and under their optimal conditions, increased 5 min after high frequency stimulation of vestibular afferents, inducing LTP in the medial vestibular nuclei. The activity of phosphatidylcholine-synthesizing phosphocholinetransferase, was not affected. Sixty minutes from the induction of LTP, PAF-PCT activity, but not that of lysoPAF-AT, was still significantly higher with respect to 5 min test stimulated control. We used AP-5 to verify whether this increase was strictly dependent upon LTP induction, which requires NMDA receptor activation. In AP-5 treated slices, lysoPAF-acetyltransferase and PAF-synthesizing phosphocholinetransferase activities increased, but they were reduced after high frequency stimulation under AP-5. In conclusion, we have demonstrated that the activities of PAF-synthesizing enzymes are activated soon after the induction of LTP and that this effect is linked to the activation of NMDA-receptors. We suggest that the enzyme activation by AP-5, preventing LTP, might be due to glutamate enhancement but, in neurons showing LTP and under normal conditions, the activation of potentiation mechanisms is critical for the enhancement of enzyme activities.

  18. Merging DBS with viral vector or stem cell implantation: “hybrid” stereotactic surgery as an evolution in the surgical treatment of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Nathan C Rowland

    2016-01-01

    Full Text Available Parkinson's disease (PD is a complex neurodegenerative disorder that is currently managed using a broad array of symptom-based strategies. However, targeting its molecular origins represents the potential to discover disease-modifying therapies. Deep brain stimulation (DBS, a highly successful treatment modality for PD symptoms, addresses errant electrophysiological signaling pathways in the basal ganglia. In contrast, ongoing clinical trials testing gene and cell replacement therapies propose to protect or restore neuronal-based physiologic dopamine transmission in the striatum. Given promising new platforms to enhance target localization'such as interventional MRI-guided stereotaxy'the opportunity now exists to create hybrid therapies that combine DBS with gene therapy and/or cell implantation. In this mini-review, we discuss approaches used for central nervous system biologic delivery in PD patients in previous trials and propose a new set of strategies based on novel molecular targets. A multifaceted approach, if successful, may not only contribute to our understanding of PD pathology but could introduce a new era of disease modification.

  19. 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.

  20. 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.

  1. Analog and digital filtering of the brain stem auditory evoked response.

    Science.gov (United States)

    Kavanagh, K T; Franks, R

    1989-07-01

    This study compared the filtering effects on the auditory evoked potential of zero and standard phase shift digital filters (the former was a mathematical approximation of a standard Butterworth filter). Conventional filters were found to decrease the height of the evoked response in the majority of waveforms compared to zero phase shift filters. A 36-dB/octave zero phase shift high pass filter with a cutoff frequency of 100 Hz produced a 16% reduction in wave amplitude compared to the unfiltered control. A 36-dB/octave, 100-Hz standard phase shift high pass filter produced a 41% reduction, and a 12-dB/octave, 150-Hz standard phase shift high pass filter produced a 38% reduction in wave amplitude compared to the unfiltered control. A decrease in the mean along with an increase in the variability of wave IV/V latency was also noted with conventional compared to zero phase shift filters. The increase in the variability of the latency measurement was due to the difficulty in waveform identification caused by the phase shift distortion of the conventional filter along with the variable decrease in wave latency caused by phase shifting responses with different spectral content. Our results indicated that a zero phase shift high pass filter of 100 Hz was the most desirable filter studied for the mitigation of spontaneous brain activity and random muscle artifact.

  2. Lineage analysis of quiescent regenerative stem cells in the adult brain by genetic labelling reveals spatially restricted neurogenic niches in the olfactory bulb.

    Science.gov (United States)

    Giachino, Claudio; Taylor, Verdon

    2009-07-01

    The subventricular zone (SVZ) of the lateral ventricles is the major neurogenic region in the adult mammalian brain, harbouring neural stem cells within defined niches. The identity of these stem cells and the factors regulating their fate are poorly understood. We have genetically mapped a population of Nestin-expressing cells during postnatal development to study their potential and fate in vivo. Taking advantage of the recombination characteristics of a nestin::CreER(T2) allele, we followed a subpopulation of neural stem cells and traced their fate in a largely unrecombined neurogenic niche. Perinatal nestin::CreER(T2)-expressing cells give rise to multiple glial cell types and neurons, as well as to stem cells of the adult SVZ. In the adult SVZ nestin::CreER(T2)-expressing neural stem cells give rise to several neuronal subtypes in the olfactory bulb (OB). We addressed whether the same population of neural stem cells play a role in SVZ regeneration. Following anti-mitotic treatment to eliminate rapidly dividing progenitors, relatively quiescent nestin::CreER(T2)-targeted cells are spared and contribute to SVZ regeneration, generating new proliferating precursors and neuroblasts. Finally, we have identified neurogenic progenitors clustered in ependymal-like niches within the rostral migratory stream (RMS) of the OB. These OB-RMS progenitors generate neuroblasts that, upon transplantation, graft, migrate and differentiate into granule and glomerular neurons. In summary, using conditional lineage tracing we have identified neonatal cells that are the source of neurogenic and regenerative neural stem cells in the adult SVZ and occupy a novel neurogenic niche in the OB.

  3. Brain stem origins of spinal projections in the lizard Tupinambis nigropunctatus.

    Science.gov (United States)

    Cruce, W L; Newman, D B

    1981-05-10

    In order to study brainstem origins of spinal projections, ten Tegu lizards (Tupinambis nigropunctatus) received complete or partial hemisections of the spinal cord at the first or second cervical segment. Their brains were processed for conventional Nissl staining. The sections were surveyed for the presence or absence of retrograde chromatolysis. Based on analysis and comparison of results from lesions in the various spinal cord funiculi, the following conclusions were reached: The interstitial nucleus projects ipsilaterally to the spinal cord via the medial longitudinal fasciculus, as does the middle reticular field of the metencephalon. The red nucleus and dorsal vagal motor nucleus both project contralaterally to the spinal cord via the dorsal part of the lateral funiculus. The superior reticular field in the rostral metencephalon and the ventrolateral vestibular nucleus project ipsilaterally to the spinal cord via the ventral funiculus. The dorsolateral metencephalic nucleus and the ventral part of the inferior reticular nucleus of the myelencephalon both project ipsilaterally to the spinal cord via the dorsal part of the lateral funiculus. Several brainstem nuclei in Tupinambis project bilaterally to the spinal cord. The ventrolateral metencephalic nucleus, for example, projects ipsilaterally to the cord via the medial longitudinal fasciculus and contralaterally via the dorsal part of the lateral funiculus. The dorsal part of the inferior reticular nucleus projects bilaterally to the spinal cord via the dorsal part of the lateral funiculus. The nucleus solitarius complex projects contralaterally via the dorsal part of the lateral funiculus but ipsilaterally via the middle of the lateral funiculus. The inferior raphe nucleus projects bilaterally to the spinal cord via the middle part of the lateral funiculus. These data suggest that supraspinal projections in reptiles, especially reticulospinal systems, are more highly differentiated than previously thought

  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 stem auditory potentials evoked by clicks in the presence of high-pass filtered noise in dogs.

    Science.gov (United States)

    Poncelet, L; Deltenre, P; Coppens, A; Michaux, C; Coussart, E

    2006-04-01

    This study evaluates the effects of a high-frequency hearing loss simulated by the high-pass-noise masking method, on the click-evoked brain stem-evoked potentials (BAEP) characteristics in dogs. BAEP were obtained in response to rarefaction and condensation click stimuli from 60 dB normal hearing level (NHL, corresponding to 89 dB sound pressure level) to wave V threshold, using steps of 5 dB in eleven 58 to 80-day-old Beagle puppies. Responses were added, providing an equivalent to alternate polarity clicks, and subtracted, providing the rarefaction-condensation potential (RCDP). The procedure was repeated while constant level, high-pass filtered (HPF) noise was superposed to the click. Cut-off frequencies of the successively used filters were 8, 4, 2 and 1 kHz. For each condition, wave V and RCDP thresholds, and slope of the wave V latency-intensity curve (LIC) were collected. The intensity range at which RCDP could not be recorded (pre-RCDP range) was calculated. Compared with the no noise condition, the pre-RCDP range significantly diminished and the wave V threshold significantly increased when the superposed HPF noise reached the 4 kHz area. Wave V LIC slope became significantly steeper with the 2 kHz HPF noise. In this non-invasive model of high-frequency hearing loss, impaired hearing of frequencies from 8 kHz and above escaped detection through click BAEP study in dogs. Frequencies above 13 kHz were however not specifically addressed in this study.

  6. Brain responses to language-relevant musical features in adolescent cochlear implant users before and after an intensive music training program

    DEFF Research Database (Denmark)

    Petersen, Bjørn; Weed, Ethan; Hansen, Mads

    Brain responses to language-relevant musical features in adolescent cochlear implant users before and after an intensive music training program Petersen B.1,2, Weed E.1,3, Hansen M.1,4, Sørensen S.D.3 , Sandmann P.5 , Vuust P.1,2 1Center of Functionally Integrative Neuroscience, Aarhus University......, rhythm and intensity). Difference waves for the rhythm deviant were analyzed in the time window between 300 and 320 ms. Separate mixed-model ANOVAs were performed for left and right fronto-central electrodes. Paired t-tests were used to analyze the behavioral data. Here we present preliminary analyses...... of ERP responses to the rhythm deviant stimuli and results from a behavioral rhythm discrimination test. For both left and right electrode sites we found a main effect of group, driven by higher mean amplitude in the NH group. There was no main effect of training. Left hemisphere sites showed...

  7. Demonstration of ipsilateral brain activation by noise in patients profoundly deaf with cochlear implant, or unilaterally deaf

    International Nuclear Information System (INIS)

    Herzog, H.; Wieler, H.; Morgenstern, C.; Lipman, J.; Langen, K.-J.; Schmid, A.; Rota, E.; Patton, D.; Feinendegen, L.F.

    1986-01-01

    Two groups of patients with hearing handicaps have been investigated with PET and F-18-2-FDG. Since these patients were unilaterally deaf or profoundly deaf with a cochlear implant installed, monaural stimulation was possible excluding any effects of bone conduction to the contralateral ear. White noise was used as acoustic stimulus in unilaterally deaf patients. The peripheral auditory nerve of cochlear implant patients was stimulated by electrical impulses which were encoded from music or a 4-tone mixture by an electronic speech processor. The non-music stimuli were chosen to avoid associative cortical reactions. In both groups response to the stimuli by increase of glucose consumption (LCMRglc) was found not only in the contralateral primary auditory cortex as expected from neuroanatomical knowledge, but also in the ipsilateral auditory cortex. Furthermore there was no correlation between the hemisphere showing increased LCMRglc and the side of stimulation or the type of stimulus. The similarity of results obtained in both groups by acoustical and electrical stimulation of the auditory nerve suggests that this kind of measurement might be a tool to predict or check the performance of a cochlear implant in a profoundly deaf patient. The finding of increased LCMRglc in the area of the normal auditory cortex in patients profoundly deaf since birth contradicts the hypothesis of degeneration of this cortical center in such patients. (Author)

  8. 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.

  9. 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

  10. Feasibility, safety, and potential demand of emergent brain magnetic resonance imaging of patients with cardiac implantable electronic devices

    Directory of Open Access Journals (Sweden)

    Maki Ono

    2017-10-01

    Conclusions: Our study found the potential demand of brain MRI of patients with CIEDs in emergency situations compared with scheduled scanning, which was shown to be feasible and safe for the diagnosis and treatment of an acute stroke.

  11. Can adult neural stem cells create new brains? Plasticity in the adult mammalian neurogenic niches: realities and expectations in the era of regenerative biology.

    Science.gov (United States)

    Kazanis, Ilias

    2012-02-01

    Since the first experimental reports showing the persistence of neurogenic activity in the adult mammalian brain, this field of neurosciences has expanded significantly. It is now widely accepted that neural stem and precursor cells survive during adulthood and are able to respond to various endogenous and exogenous cues by altering their proliferation and differentiation activity. Nevertheless, the pathway to therapeutic applications still seems to be long. This review attempts to summarize and revisit the available data regarding the plasticity potential of adult neural stem cells and of their normal microenvironment, the neurogenic niche. Recent data have demonstrated that adult neural stem cells retain a high level of pluripotency and that adult neurogenic systems can switch the balance between neurogenesis and gliogenesis and can generate a range of cell types with an efficiency that was not initially expected. Moreover, adult neural stem and precursor cells seem to be able to self-regulate their interaction with the microenvironment and even to contribute to its synthesis, altogether revealing a high level of plasticity potential. The next important step will be to elucidate the factors that limit this plasticity in vivo, and such a restrictive role for the microenvironment is discussed in more details.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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).

  17. PET Mapping for Brain-Computer Interface Stimulation of the Ventroposterior Medial Nucleus of the Thalamus in Rats with Implanted Electrodes.

    Science.gov (United States)

    Zhu, Yunqi; Xu, Kedi; Xu, Caiyun; Zhang, Jiacheng; Ji, Jianfeng; Zheng, Xiaoxiang; Zhang, Hong; Tian, Mei

    2016-07-01

    Brain-computer interface (BCI) technology has great potential for improving the quality of life for neurologic patients. This study aimed to use PET mapping for BCI-based stimulation in a rat model with electrodes implanted in the ventroposterior medial (VPM) nucleus of the thalamus. PET imaging studies were conducted before and after stimulation of the right VPM. Stimulation induced significant orienting performance. (18)F-FDG uptake increased significantly in the paraventricular thalamic nucleus, septohippocampal nucleus, olfactory bulb, left crus II of the ansiform lobule of the cerebellum, and bilaterally in the lateral septum, amygdala, piriform cortex, endopiriform nucleus, and insular cortex, but it decreased in the right secondary visual cortex, right simple lobule of the cerebellum, and bilaterally in the somatosensory cortex. This study demonstrated that PET mapping after VPM stimulation can identify specific brain regions associated with orienting performance. PET molecular imaging may be an important approach for BCI-based research and its clinical applications. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  18. Ion implantation

    International Nuclear Information System (INIS)

    Dearnaley, Geoffrey

    1975-01-01

    First, ion implantation in semiconductors is discussed: ion penetration, annealing of damage, gettering, ion implanted semiconductor devices, equipement requirements for ion implantation. The importance of channeling for ion implantation is studied. Then, some applications of ion implantation in metals are presented: study of the corrosion of metals and alloys; influence or ion implantation on the surface-friction and wear properties of metals; hyperfine interactions in implanted metals

  19. Monte Carlo simulations for dose enhancement in cancer treatment using bismuth oxide nanoparticles implanted in brain soft tissue.

    Science.gov (United States)

    Taha, Eslam; Djouider, Fathi; Banoqitah, Essam

    2018-03-26

    The objective of this work is to study the dosimetric performances of bismuth oxide nanoparticles implanted in tumors in cancer radiotherapy. GEANT4 based Monte Carlo numerical simulations were performed to assess dose enhancement distributions in and around a 1 × 1 × 1 cm 3 tumor implanted with different concentrations of bismuth oxide and irradiated with low energies 125 I, 131 Cs, and 103 Pd radioactive sources. Dose contributions were considered from photoelectrons, Auger electrons, and characteristic X-rays. Our results show the dose enhancement increased with increasing both bismuth oxide concentration in the target and photon energy. A dose enhancement factor up to 18.55 was obtained for a concentration of 70 mg/g of bismuth oxide in the tumor when irradiated with 131 Cs source. This study showed that bismuth oxide nanoparticles are innovative agents that could be potentially applicable to in vivo cancer radiotherapy due to the fact that they induce a highly localized energy deposition within the tumor.

  20. dp53 Restrains ectopic neural stem cell formation in the Drosophila brain in a non-apoptotic mechanism involving Archipelago and cyclin E.

    Directory of Open Access Journals (Sweden)

    Yingshi Ouyang

    Full Text Available Accumulating evidence suggests that tumor-initiating stem cells or cancer stem cells (CSCs possibly originating from normal stem cells may be the root cause of certain malignancies. How stem cell homeostasis is impaired in tumor tissues is not well understood, although certain tumor suppressors have been implicated. In this study, we use the Drosophila neural stem cells (NSCs called neuroblasts as a model to study this process. Loss-of-function of Numb, a key cell fate determinant with well-conserved mammalian counterparts, leads to the formation of ectopic neuroblasts and a tumor phenotype in the larval brain. Overexpression of the Drosophila tumor suppressor p53 (dp53 was able to suppress ectopic neuroblast formation caused by numb loss-of-function. This occurred in a non-apoptotic manner and was independent of Dacapo, the fly counterpart of the well-characterized mammalian p53 target p21 involved in cellular senescence. The observation that dp53 affected Edu incorporation into neuroblasts led us to test the hypothesis that dp53 acts through regulation of factors involved in cell cycle progression. Our results show that the inhibitory effect of dp53 on ectopic neuroblast formation was mediated largely through its regulation of Cyclin E (Cyc E. Overexpression of Cyc E was able to abrogate dp53's ability to rescue numb loss-of-function phenotypes. Increasing Cyc E levels by attenuating Archipelago (Ago, a recently identified transcriptional target of dp53 and a negative regulator of Cyc E, had similar effects. Conversely, reducing Cyc E activity by overexpressing Ago blocked ectopic neuroblast formation in numb mutant. Our results reveal an intimate connection between cell cycle progression and NSC self-renewal vs. differentiation control, and indicate that p53-mediated regulation of ectopic NSC self-renewal through the Ago/Cyc E axis becomes particularly important when NSC homeostasis is perturbed as in numb loss-of-function condition. This has

  1. Partially flexible MEMS neural probe composed of polyimide and sucrose gel for reducing brain damage during and after implantation

    International Nuclear Information System (INIS)

    Jeon, Myounggun; Yoon, Eui-Sung; Cho, Il-Joo; Cho, Jeiwon; Jung, Dahee; Kim, Yun Kyung; Shin, Sehyun

    2014-01-01

    This paper presents a flexible microelectromechanical systems (MEMS) neural probe that minimizes neuron damage and immune response, suitable for chronic recording applications. MEMS neural probes with various features such as high electrode densities have been actively investigated for neuron stimulation and recording to study brain functions. However, successful recording of neural signals in chronic application using rigid silicon probes still remains challenging because of cell death and macrophages accumulated around the electrodes over time from continuous brain movement. Thus, in this paper, we propose a new flexible MEMS neural probe that consists of two segments: a polyimide-based, flexible segment for connection and a rigid segment composed of thin silicon for insertion. While the flexible connection segment is designed to reduce the long-term chronic neuron damage, the thin insertion segment is designed to minimize the brain damage during the insertion process. The proposed flexible neural probe was successfully fabricated using the MEMS process on a silicon on insulator wafer. For a successful insertion, a biodegradable sucrose gel is coated on the flexible segment to temporarily increase the probe stiffness to prevent buckling. After the insertion, the sucrose gel dissolves inside the brain exposing the polyimide probe. By performing an insertion test, we confirm that the flexible probe has enough stiffness. In addition, by monitoring immune responses and brain histology, we successfully demonstrate that the proposed flexible neural probe incurs fivefold less neural damage than that incurred by a conventional silicon neural probe. Therefore, the presented flexible neural probe is a promising candidate for recording stable neural signals for long-time chronic applications. (paper)

  2. 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

  3. SU-F-T-43: Prediction of Dose Increments by Brain Metastases Resection Cavity Shrinkage Model with I-125 and Cs-131 LDR Seed Implantations

    Energy Technology Data Exchange (ETDEWEB)

    Han, D; Braunstein, S; Sneed, P; McDermott, M; Ma, L [University of California San Francisco, San Francisco, CA (United States)

    2016-06-15

    Purpose: This work aims to determine dose variability via a brain metastases resection cavity shrinkage model (RC-SM) with I-125 or Cs-131 LDR seed implantations. Methods: The RC-SM was developed to represent sequential volume changes of 95 consecutive brain metastases patients. All patients underwent serial surveillance MR and change in cavity volume was recorded for each patient. For the initial resection cavity, a prolate-ellipsoid cavity model was suggested and applied volume shrinkage rates to correspond to 1.7, 3.6, 5.9, 11.7, and 20.5 months after craniotomy. Extra-ring structure (6mm) was added on a surface of the resection volume and the same shrinkage rates were applied. Total 31 LDR seeds were evenly distributed on the surface of the resection cavity. The Amersham 6711 I-125 seed model (Oncura, Arlington Heights, IL) and the Model Cs-1 Rev2 Cs-131 seed model (IsoRay, Richland, WA) were used for TG-43U1 dose calculation and in-house-programed 3D-volumetric dose calculation system was used for resection cavity rigid model (RC-RM) and the RC-SM dose calculation. Results: The initial resection cavity volume shrunk to 25±6%, 35±6.8%, 42±7.7%, 47±9.5%, and 60±11.6%, with respect to sequential MR images post craniotomy, and the shrinkage rate (SR) was calculated as SR=56.41Xexp(−0.2024Xt)+33.99 and R-square value was 0.98. The normal brain dose as assessed via the dose to the ring structure with the RC-SM showed 29.34% and 27.95% higher than the RC-RM, I-125 and Cs-131, respectively. The dose differences between I-125 and Cs-131 seeds within the same models, I-125 cases were 9.17% and 10.35% higher than Cs-131 cases, the RC-RM and the RC-SM, respectively. Conclusion: A realistic RC-SM should be considered during LDR brain seed implementation and post-implement planning to prevent potential overdose. The RC-SM calculation shows that Cs-131 is more advantageous in sparing normal brain as the resection cavity volume changes with the LDR seeds implementation.

  4. 5-Fluorouracil and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) followed by hydroxyurea, misonidazole, and irradiation for brain stem gliomas: a pilot study of the Brain Tumor Research Center and the Childrens Cancer Group

    International Nuclear Information System (INIS)

    Levin, V.A.; Edwards, M.S.; Wara, W.M.; Allen, J.; Ortega, J.; Vestnys, P.

    1984-01-01

    Twenty-eight evaluable children with the diagnosis of brain stem glioma were treated with 5-fluorouracil and CCNU before posterior fossa irradiation (5500 rads); during irradiation, the children received hydroxyurea and misonidazole. The treatment was well tolerated, and minimal toxicity was produced. The median relapse-free survival was 32 weeks, and the median survival was 44 weeks. Analysis of covariates showed that, in patients between the ages of 2 and 19 years, survival was longest in the older children (P less than 0.02). Tumor histology, sex, extent of operation (if any), Karnofsky score, and radiation dose did not correlate with survival

  5. Effects of congruent and incongruent visual cues on speech perception and brain activity in cochlear implant users.

    Science.gov (United States)

    Song, Jae-Jin; Lee, Hyo-Jeong; Kang, Hyejin; Lee, Dong Soo; Chang, Sun O; Oh, Seung Ha

    2015-03-01

    While deafness-induced plasticity has been investigated in the visual and auditory domains, not much is known about language processing in audiovisual multimodal environments for patients with restored hearing via cochlear implant (CI) devices. Here, we examined the effect of agreeing or conflicting visual inputs on auditory processing in deaf patients equipped with degraded artificial hearing. Ten post-lingually deafened CI users with good performance, along with matched control subjects, underwent H 2 (15) O-positron emission tomography scans while carrying out a behavioral task requiring the extraction of speech information from unimodal auditory stimuli, bimodal audiovisual congruent stimuli, and incongruent stimuli. Regardless of congruency, the control subjects demonstrated activation of the auditory and visual sensory cortices, as well as the superior temporal sulcus, the classical multisensory integration area, indicating a bottom-up multisensory processing strategy. Compared to CI users, the control subjects exhibited activation of the right ventral premotor-supramarginal pathway. In contrast, CI users activated primarily the visual cortices more in the congruent audiovisual condition than in the null condition. In addition, compared to controls, CI users displayed an activation focus in the right amygdala for congruent audiovisual stimuli. The most notable difference between the two groups was an activation focus in the left inferior frontal gyrus in CI users confronted with incongruent audiovisual stimuli, suggesting top-down cognitive modulation for audiovisual conflict. Correlation analysis revealed that good speech performance was positively correlated with right amygdala activity for the congruent condition, but negatively correlated with bilateral visual cortices regardless of congruency. Taken together these results suggest that for multimodal inputs, cochlear implant users are more vision-reliant when processing congruent stimuli and are disturbed

  6. Modeling Group B Streptococcus and Blood-Brain Barrier Interaction by Using Induced Pluripotent Stem Cell-Derived Brain Endothelial Cells

    OpenAIRE

    Kim, Brandon J.; Bee, Olivia B.; McDonagh, Maura A.; Stebbins, Matthew J.; Palecek, Sean P.; Doran, Kelly S.; Shusta, Eric V.

    2017-01-01

    ABSTRACT Bacterial meningitis is a serious infection of the central nervous system (CNS) that occurs after bacteria interact with and penetrate the blood-brain barrier (BBB). The BBB is comprised of highly specialized brain microvascular endothelial cells (BMECs) that function to separate the circulation from the CNS and act as a formidable barrier for toxins and pathogens. Certain bacteria, such as Streptococcus agalactiae (group B Streptococcus [GBS]), possess the ability to interact with a...

  7. Melatonin disturbs SUMOylation mediated crosstalk between c-Myc and Nestin via MT1 activation and promotes the sensitivity of Paclitaxel in brain cancer stem cells.

    Science.gov (United States)

    Lee, Hyemin; Lee, Hyo-Jung; Jung, Ji Hoon; Shin, Eun Ah; Kim, Sung-Hoon

    2018-04-14

    Here the underlying antitumor mechanism of melatonin and its potency as a sensitizer of Paclitaxel was investigated in X02 cancer stem cells. Melatonin suppressed sphere formation and induced G2/M arrest in X02 cells expressing Nestin, CD133, CXCR4 and SOX-2 as biomarkers of stemness. Furthermore, melatonin reduced the expression of CDK2, CDK4, cyclin D1, cyclin E, and c-Myc and upregulated cyclin B1 in X02 cells. Notably, genes of c-Myc related mRNAs were differentially expressed in melatonin treated X02 cells by microarray analysis. Consistently, melatonin reduced the expression of c-Myc at mRNA and protein levels, which was blocked by MG132. Of note, overexpression of c-Myc increased the expression of Nestin, while overexpression of Nestin enhanced c-Myc through crosstalk despite different locations, nucleus and cytoplasm. Interestingly, melatonin attenuated small ubiquitin-related modifier-1 (SUMO-1) more than SUMO-2 or SUMO-3 and disturbed nuclear translocation of Nestin for direct binding to c-Myc by SUMOylation of SUMO-1 protein by immunofluorescence and immunoprecipitation. Also, melatonin reduced trimethylated histone H3K4me3 and H3K36me3 more than dimethylation in X02 cells by Western blotting and Chromatin immunoprecipitation assay. Notably, melatonin upregulated MT1, not MT2, in X02 cells and melatonin receptor inhibitor Luzindole blocked the ability of melatonin to decrease the expression of Nestin, p-c-Myc(S62) and c-Myc. Furthermore, melatonin promoted cytotoxicity, sub G1 accumulation and apoptotic body formation by Paclitaxcel in X02 cells. Taken together, these findings suggest that melatonin inhibits stemness via suppression of c-Myc, Nestin, and histone methylation via MT1 activation and promotes anticancer effect of Paclitaxcel in brain cancer stem cells. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  8. Fatal outcome after brain stem infarction related to bilateral vertebral artery occlusion - case report of a detrimental complication of cervical spine trauma

    Directory of Open Access Journals (Sweden)

    Beauchamp Kathryn M

    2011-07-01

    Full Text Available Abstract Background Vertebral artery injury (VAI after blunt cervical trauma occurs more frequently than historically believed. The symptoms due to vertebral artery (VA occlusion usually manifest within the first 24 hours after trauma. Misdiagnosed VAI or delay in diagnosis has been reported to cause acute deterioration of previously conscious and neurologically intact patients. Case presentation A 67 year-old male was involved in a motor vehicle crash (MVC sustaining multiple injuries. Initial evaluation by the emergency medical response team revealed that he was alert, oriented, and neurologically intact. He was transferred to the local hospital where cervical spine computed tomography (CT revealed several abnormalities. Distraction and subluxation was present at C5-C6 and a comminuted fracture of the left lateral mass of C6 with violation of the transverse foramen was noted. Unavailability of a spine specialist prompted the patient's transfer to an area medical center equipped with spine care capabilities. After arrival, the patient became unresponsive and neurological deficits were noted. His continued deterioration prompted yet another transfer to our Level 1 regional trauma center. A repeat cervical spine CT at our institution revealed significantly worsened subluxation at C5-C6. CT angiogram also revealed complete occlusion of bilateral VA. The following day, a repeat CT of the head revealed brain stem infarction due to bilateral VA occlusion. Shortly following, the patient was diagnosed with brain death and care was withdrawn. Conclusion Brain stem infarction secondary to bilateral VA occlusion following cervical spine trauma resulted in fatal outcome. Prompt imaging evaluation is necessary to assess for VAI in cervical trauma cases with facet joint subluxation/dislocation or transverse foramen fracture so that treatment is not delayed. Additionally, multiple transportation events are risk factors for worsening when unstable cervical

  9. Dynamic changes in oxygenation of intracranial tumor and contralateral brain during tumor growth and carbogen breathing: A multisite EPR oximetry with implantable resonators

    Science.gov (United States)

    Hou, Huagang; Dong, Ruhong; Li, Hongbin; Williams, Benjamin; Lariviere, Jean P.; Hekmatyar, S.K.; Kauppinen, Risto A.; Khan, Nadeem; Swartz, Harold

    2013-01-01

    Introduction Several techniques currently exist for measuring tissue oxygen; however technical difficulties have limited their usefulness and general application. We report a recently developed electron paramagnetic resonance (EPR) oximetry approach with multiple probe implantable resonators (IRs) that allow repeated measurements of oxygen in tissue at depths of greater than 10 mm. Methods The EPR signal to noise (S/N) ratio of two probe IRs was compared with that of LiPc deposits. The feasibility of intracranial tissue pO2 measurements by EPR oximetry using IRs was tested in normal rats and rats bearing intracerebral F98 tumors. The dynamic changes in the tissue pO2 were assessed during repeated hyperoxia with carbogen breathing. Results A 6–10 times increase in the S/N ratio was observed with IRs as compared to LiPc deposits. The mean brain pO2 of normal rats was stable and increased significantly during carbogen inhalation in experiments repeated for 3 months. The pO2 of F98 glioma declined gradually, while the pO2 of contralateral brain essentially remained the same. Although a significant increase in the glioma pO2 was observed during carbogen inhalation, this effect declined in experiments repeated over days. Conclusion EPR oximetry with IRs provides a significant increase in S/N ratio. The ability to repeatedly assess orthotopic glioma pO2 is likely to play a vital role in understanding the dynamics of tissue pO2 during tumor growth and therapies designed to modulate tumor hypoxia. This information could then be used to optimize chemoradiation by scheduling treatments at times of increased glioma oxygenation. PMID:22033225

  10. CFHR1-Modified Neural Stem Cells Ameliorated Brain Injury in a Mouse Model of Neuromyelitis Optica Spectrum Disorders.

    Science.gov (United States)

    Shi, Kaibin; Wang, Zhen; Liu, Yuanchu; Gong, Ye; Fu, Ying; Li, Shaowu; Wood, Kristofer; Hao, Junwei; Zhang, Guang-Xian; Shi, Fu-Dong; Yan, Yaping

    2016-11-01

    A major hurdle for effective stem cell therapy is ongoing inflammation in the target organ. Reconditioning the lesion microenvironment may be an effective way to promote stem cell therapy. In this study, we showed that engineered neural stem cells (NSCs) with complement factor H-related protein 1, a complement inhibitor protein, can attenuate inflammatory infiltration and immune-mediated damage of astrocytes, an important pathogenic progress in patients with neuromyelitis optica spectrum disorders. Furthermore, we demonstrated that transplantation of the complement factor H-related protein 1-modified NSCs effectively blocked the complement activation cascade and inhibited formation of the membrane attack complex, thus contributing to the protection of endogenous and transplanted NSC-differentiated astrocytes. Therefore, manipulation of the lesion microenvironment contributes to a more effective cell replacement therapeutic strategy for autoimmune diseases of the CNS. Copyright © 2016 by The American Association of Immunologists, Inc.

  11. Mesenchymal stem cell transplantation attenuates blood brain barrier damage and neuroinflammation and protects dopaminergic neurons against MPTP toxicity in the substantia nigra in a model of Parkinson's disease.

    Science.gov (United States)

    Chao, Yin Xia; He, Bei Ping; Tay, Samuel Sam Wah

    2009-11-30

    Immunomodulatory effects of transplanted mesenchymal stem cells (MSCs) in the treatment of Parkinson's disease were studied in the MPTP-induced mouse model. MPTP treatment induced a significant loss of dopaminergic neurons, decreased expressions of claudin 1, claudin 5 and occludin in the substantia nigra compacta (SNc), and functional damage of the blood brain barrier (BBB). Our study further discovered that infiltration of MBLs into the brain to bind with microglia was detected in the SNc of MPTP-treated mice, suggesting that the BBB compromise and MBL infiltration might be involved in the pathogenesis of MPTP-induced PD. In addition, MPTP treatment also increased the expression of mannose-binding lectins (MBLs) in the liver tissue. Intravenous transplantation of MSCs into MPTP-treated mice led to recovery of BBB integrity, suppression of MBL infiltration at SNc and MBL expression in the liver, suppression of microglial activation and prevention of dopaminergic neuron death. No transplanted MSCs were observed to differentiate into dopaminergic neurons, while the MSCs migrated into the SNc and released TGF-beta1 there. Therefore, intravenous transplantation of MSCs which protect dopaminergic neurons from MPTP toxicity may be engaged in anyone or a combination of these mechanisms: repair of the BBB, reduction of MBL in the brain, inhibition of microglial cytotoxicity, and direct protection of dopaminergic neurons.

  12. [Ferumoxide labeled Flk1+ CD31- CD34- human bone marrow mesenchymal stem cells and its in vivo tracing in the brains of Macaca Fascicularis].

    Science.gov (United States)

    Feng, Ming; Wang, Ren-Zhi; Zhu, Hua; Zhang, Nan; Wang, Chang-Jun; Wei, Jun-Ji; Lu, Shan; Li, Qin; Yin, Xiao-Ming; Han, Qin; Ma, Wen-Bin; Qin, Chuang; Zhao, Chun-Hua; An, Yi-Hua; Kong, Yan-Guo

    2008-10-01

    To explore the method for labeling Flk1+ CD31- CD34- human bone marrow mesenchymal stem cells (hBMSCs) with ferumoxide-PLL and evaluate the feasibility of its tracing after transplantation into the brains of Macaca Fascicularis. The hBMSCs were incubated with ferumoxide-PLL. Trypan blue staining, Prussian blue staining, and transmission electron microscope were performed to show intracellular iron, marking efficiency, and the vigor of the labeled cells. After the hBMSCs were transplanted into the brains of cynomolgus monkeys by stereotaxis, magnetic resonance imaging (MRI) was performed to trace the cells in vivo. Cell survival and differentiation were studied with immunohistochemistry, Prussian blue staining, and HE staining. The marking efficiency of the ferumoxide-PLL was 96%. Iron particles were found intracytoplasmic of the hBMSCs by Prussian blue staining and transmission electron microscopy. The relaxation rates of labeled cells in MRI were 4.4 and 4.2 times higher than those of the unlabeled cells. Hypointensity area was found by MRI three weeks after transplantation. Many hBMSCs and new vessels were found in the transplantation zone by pathological and immunofluorescence methods. Ferumoxide-PLL can effectively label hBMSCs and thus increase its contrast in MRI results. The cells can survive in the brains of cynomolgus monkeys. The labeled hBMSCs can be traced in vivo by MRI.

  13. 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.

  14. 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...

  15. 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.

  16. Functional recovery after injury of motor cortex in rats: effects of rehabilitation and stem cell transplantation in a traumatic brain injury model of cortical resection.

    Science.gov (United States)

    Lee, Do-Hun; Lee, Ji Yeoun; Oh, Byung-Mo; Phi, Ji Hoon; Kim, Seung-Ki; Bang, Moon Suk; Kim, Seung U; Wang, Kyu-Chang

    2013-03-01

    Experimental studies and clinical trials designed to help patients recover from various brain injuries, such as stroke or trauma, have been attempted. Rehabilitation has shown reliable, positive clinical outcome in patients with various brain injuries. Transplantation of exogenous neural stem cells (NSCs) to repair the injured brain is a potential tool to help patient recovery. This study aimed to evaluate the therapeutic efficacy of a combination therapy consisting of rehabilitation and NSC transplantation compared to using only one modality. A model of motor cortex resection in rats was used to create brain injury in order to obtain consistent and prolonged functional deficits. The therapeutic results were evaluated using three methods during an 8-week period with a behavioral test, motor-evoked potential (MEP) measurement, and measurement of the degree of endogenous NSC production. All three treatment groups showed the effects of treatment in the behavioral test, although the NSC transplantation alone group (CN) exhibited slightly worse results than the rehabilitation alone group (CR) or the combination therapy group (CNR). The latency on MEP was shortened to a similar extent in all three groups compared to the untreated group (CO). However, the enhancement of endogenous NSC proliferation was dramatically reduced in the CN group compared not only to the CR and CNR groups but also to the CO group. The CR and CNR groups seemed to prolong the duration of endogenous NSC proliferation compared to the untreated group. A combination of rehabilitation and NSC transplantation appears to induce treatment outcomes that are similar to rehabilitation alone. Further studies are needed to evaluate the electrophysiological outcome of recovery and the possible effect of prolonging endogenous NSC proliferation in response to NSC transplantation and rehabilitation.

  17. Validation of the 133Xe inhalation method for measuring brain stem and cerebellar blood flow in human subjects and the baboon

    International Nuclear Information System (INIS)

    Sakai, F.; Meyer, J. St.; Yamaguchi, F.; Yamamoto, M.; Shaw, T.; Juge, O.

    1979-01-01

    Regional cerebral blood flow (rCBF) measurements recorded by probes placed over the posterior fossa after 133 Xe inhalation have been validated here in. After inhalation, 133 Xe gas is distributed via arterial blood of both carotid an vertebrobasilar systems, so that it should be possible to measure rCBF of the brain stem and cerebellum if appropriate collimation, probe placement and selection of activity are employed. Detectors placed over the suboccipital regions may be subject to distortion by radioactivity derived from extracerebral sources so that the following questions were asked: 1) What is the counting geometry for each probe looking at this area 2) What is the extent of contamination from surrounding tissues 3) Are the flow values reproducible and in accordance with values obtained by other techniques 4) Are the flow values able to show predictable changes under physiological and pathological conditions Animal and human experiments designed to answer these questions are reported. (Auth.)

  18. A clinico-radiological study on 254 cases of pontine high signals on magnetic resonance imaging in relation to brain stem semiology

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Masaki; Takahashi, Akira (Nagoya Univ. (Japan). Faculty of Medicine); Arahata, Yutaka; Motegi, Yoshimasa; Furuse, Masahiro

    1993-11-01

    A total of 254 patients who were proved to have pontine high intensity areas on T[sub 2]-weighted magnetic resonance imaging (MRI) were analyzed in relation to brain stem semiology. A comparative study on MRI and MR angiography was made between 254 patients with pontine high signals and 276 control cases showing no abnormality either on T[sub 1] or T[sub 2]-weighted images. Of the 254 patients, 62 had transient subjective complaints such as vertigo-dizziness. Supratentorial high signals, basilar artery tortuousness and vertebral artery asymmetry on MR angiography were seen more frequently in patients with pontine high signals than in the controls. In conclusion, pontine high signals may result from diffuse arteriosclerosis and MR angiography is considered to be a useful screening method. (author).

  19. Anti-Ma2 antibody related paraneoplastic limbic/brain stem encephalitis associated with breast cancer expressing Ma1, Ma2, and Ma3 mRNAs.

    Science.gov (United States)

    Sahashi, K; Sakai, K; Mano, K; Hirose, G

    2003-09-01

    A 69 year old woman presented with cognitive impairment and supranuclear gaze palsy caused by paraneoplastic limbic/brain stem encephalitis associated with atypical medullary breast carcinoma. The cerebrospinal fluid from the patient harboured an anti-neuronal cell antibody against Ma2 antigen, but not against Ma1 or Ma3 antigen. Despite the antibody being restricted to the Ma2 antigen, the patient's cancer tissue expressed Ma1, Ma2, and Ma3 mRNAs. These results, and the expression of Ma2 mRNA in an atypical medullar breast carcinoma in another patient without paraneoplastic encephalitis, indicate that the induction of anti-Ma2 antibody depends on host immunoreponsiveness and not on the presence of the antigen itself in the cancer.

  20. Brain stem slice conditioned medium contains endogenous BDNF and GDNF that affect neural crest boundary cap cells in co-culture.

    Science.gov (United States)

    Kaiser, Andreas; Kale, Ajay; Novozhilova, Ekaterina; Siratirakun, Piyaporn; Aquino, Jorge B; Thonabulsombat, Charoensri; Ernfors, Patrik; Olivius, Petri

    2014-05-30

    Conditioned medium (CM), made by collecting medium after a few days in cell culture and then re-using it to further stimulate other cells, is a known experimental concept since the 1950s. Our group has explored this technique to stimulate the performance of cells in culture in general, and to evaluate stem- and progenitor cell aptitude for auditory nerve repair enhancement in particular. As compared to other mediums, all primary endpoints in our published experimental settings have weighed in favor of conditioned culture medium, where we have shown that conditioned culture medium has a stimulatory effect on cell survival. In order to explore the reasons for this improved survival we set out to analyze the conditioned culture medium. We utilized ELISA kits to investigate whether brain stem (BS) slice CM contains any significant amounts of brain-derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF). We further looked for a donor cell with progenitor characteristics that would be receptive to BDNF and GDNF. We chose the well-documented boundary cap (BC) progenitor cells to be tested in our in vitro co-culture setting together with cochlear nucleus (CN) of the BS. The results show that BS CM contains BDNF and GDNF and that survival of BC cells, as well as BC cell differentiation into neurons, were enhanced when BS CM were used. Altogether, we conclude that BC cells transplanted into a BDNF and GDNF rich environment could be suitable for treatment of a traumatized or degenerated auditory nerve. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Brain-Derived Neurotrophic Factor Loaded PS80 PBCA Nanocarrier for In Vitro Neural Differentiation of Mouse Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Chiu-Yen Chung

    2017-03-01

    Full Text Available Brain derived neurotrophic factor (BDNF can induce neural differentiation in stem cells and has the potential for repair of the nervous system. In this study, a polysorbate 80-coated polybutylcyanoacrylate nanocarrier (PS80 PBCA NC was constructed to deliver plasmid DNAs (pDNAs containing BDNF gene attached to a hypoxia-responsive element (HRE-cmvBDNF. The hypoxia-sensing mechanism of BDNF expression and inductiveness of the nano-formulation on mouse induced pluripotent stem cells (iPSCs to differentiate into neurons following hypoxia was tested in vitro with immunofluorescent staining and Western blotting. The HRE-cmvBDNF appeared to adsorb onto the surface of PS80 PBCA NC, with a resultant mean diameter of 92.6 ± 1.0 nm and zeta potential of −14.1 ± 1.1 mV. HIF-1α level in iPSCs was significantly higher in hypoxia, which resulted in a 51% greater BDNF expression when transfected with PS80 PBCA NC/HRE-cmvBDNF than those without hypoxia. TrkB and phospho-Akt were also elevated which correlated with neural differentiation. The findings suggest that PS80 PBCA NC too can be endocytosed to serve as an efficient vector for genes coupled to the HRE in hypoxia-sensitive cells, and activation of the PI3/Akt pathway in iPSCs by BDNF is capable of neural lineage specification.

  2. Lymphocytic infundibulo-neurohypophysitis (LINH) with involvement of the hypothalamus and with coexistent focal infiltration of the brain stem: A case report

    International Nuclear Information System (INIS)

    Spalek, M.; Kowalska, A.

    2006-01-01

    Autoimmune (lymphocytic) hypophysitis is a rare disease. It was originally labeled lymphocytic adenohypophysitis (LAH) and was first described in 1962. However, when it was later realized that the autoimmune infiltrate could exclusively involve the infundibular stem and the posterior lobe, the term lymphocytic infundibulo-neurohypophysitis (LINH) was created. Review of the literature identified 39 patients with LINH, 245 with LAH, and 95 with LPH (lymphocytic pan-hypophysitis) to date. The authors present the case of a 19-year-old woman with acute bacterial infection previous to symptoms of hypopituitarism. CT and MR imaging showed tumor-like areas of intensive post-contrast enhancement without edema in the suprasellar region and in the brain stem. Based on the diagnostic investigations, LINH was diagnosed. Germinoma, sarcoidosis, tuberculosis, and bacterial hypophysitis were excluded in the diagnostic differentiation. Regression of clinical and radiological symptoms was observed after corticotherapy. Lymphocytic infundibulo-neurohypophysitis is a rare disease that should be considered in the differential diagnosis of any suprasellar and/or intrasellar mass. (author)

  3. Comparison of intraspinal and intrathecal implantation of induced pluripotent stem cell-derived neural precursors for the treatment of spinal cord injury in rats

    Czech Academy of Sciences Publication Activity Database

    Amemori, Takashi; Růžička, Jiří; Romanyuk, Nataliya; Jhanwar-Uniyal, M.; Syková, Eva; Jendelová, Pavla

    2015-01-01

    Roč. 6, Dec (2015), s. 257 ISSN 1757-6512 R&D Projects: GA MŠk(CZ) LH12024 Institutional support: RVO:68378041 Keywords : spinal cord injury * human induced pluripotent stem cells * cell therapy * cell application route Subject RIV: FH - Neurology Impact factor: 4.504, year: 2015

  4. Study of temperature and radiation induced microstructural changes in Xe-implanted UO2 by TEM, STEM, SIMS and positron spectroscopy

    International Nuclear Information System (INIS)

    Djourelov, Nikolay; Marchand, Benoît; Marinov, Hristo; Moncoffre, Nathalie; Pipon, Yves; Bérerd, Nicolas; Nédélec, Patrick; Raimbault, Louis; Epicier, Thierry

    2013-01-01

    Doppler broadening of annihilation gamma-line combined with a slow positron beam (SPB) was used to measure the momentum density distribution of annihilating pairs in a set of sintered UO 2 samples implantated with 800-keV 136 Xe 2+ at fluences of 1 × 10 15 and 1 × 10 16 Xe cm −2 . The effect of prolonged post-implantation annealing at 1673 and 1873 K, grain size, and 152-MeV Iodine irradiation were studied by analysis of S(E) profiles and S-W maps and discussed versus secondary ion mass spectroscopy (SIMS), scanning transmission electron microscopy results. Spectroscopy with SPB and SIMS is an excellent combination of complementary techniques for studying the formation and evolution of Xe-bubbles, and Xe retention

  5. Viral infection of implanted meningeal tumors induces antitumor memory T-cells to travel to the brain and eliminate established tumors.

    Science.gov (United States)

    Gao, Yanhua; Whitaker-Dowling, Patricia; Barmada, Mamdouha A; Basse, Per H; Bergman, Ira

    2015-04-01

    Leptomeningeal metastases occur in 2%-5% of patients with breast cancer and have an exceptionally poor prognosis. The blood-brain and blood-meningeal barriers severely inhibit successful chemotherapy. We have developed a straightforward method to induce antitumor memory T-cells using a Her2/neu targeted vesicular stomatitis virus. We sought to determine whether viral infection of meningeal tumor could attract antitumor memory T-cells to eradicate the tumors. Meningeal implants in mice were studied using treatment trials and analyses of immune cells in the tumors. This paper demonstrates that there is a blood-meningeal barrier to bringing therapeutic memory T-cells to meningeal tumors. The barrier can be overcome by viral infection of the tumor. Viral infection of the meningeal tumors followed by memory T-cell transfer resulted in 89% cure of meningeal tumor in 2 different mouse strains. Viral infection produced increased infiltration and proliferation of transferred memory T-cells in the meningeal tumors. Following viral infection, the leukocyte infiltration in meninges and tumor shifted from predominantly macrophages to predominantly T-cells. Finally, this paper shows that successful viral therapy of peritoneal tumors generates memory CD8 T-cells that prevent establishment of tumor in the meninges of these same animals. These results support the hypothesis that a virally based immunization strategy can be used to both prevent and treat meningeal metastases. The meningeal barriers to cancer therapy may be much more permeable to treatment based on cells than treatment based on drugs or molecules. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Clinical Trial of Human Fetal Brain-Derived Neural Stem/Progenitor Cell Transplantation in Patients with Traumatic Cervical Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Ji Cheol Shin

    2015-01-01

    Full Text Available In a phase I/IIa open-label and nonrandomized controlled clinical trial, we sought to assess the safety and neurological effects of human neural stem/progenitor cells (hNSPCs transplanted into the injured cord after traumatic cervical spinal cord injury (SCI. Of 19 treated subjects, 17 were sensorimotor complete and 2 were motor complete and sensory incomplete. hNSPCs derived from the fetal telencephalon were grown as neurospheres and transplanted into the cord. In the control group, who did not receive cell implantation but were otherwise closely matched with the transplantation group, 15 patients with traumatic cervical SCI were included. At 1 year after cell transplantation, there was no evidence of cord damage, syrinx or tumor formation, neurological deterioration, and exacerbating neuropathic pain or spasticity. The American Spinal Injury Association Impairment Scale (AIS grade improved in 5 of 19 transplanted patients, 2 (A → C, 1 (A → B, and 2 (B → D, whereas only one patient in the control group showed improvement (A → B. Improvements included increased motor scores, recovery of motor levels, and responses to electrophysiological studies in the transplantation group. Therefore, the transplantation of hNSPCs into cervical SCI is safe and well-tolerated and is of modest neurological benefit up to 1 year after transplants. This trial is registered with Clinical Research Information Service (CRIS, Registration Number: KCT0000879.

  7. Mobilization of stem cell with granulocyte-colony stimulating factor promotes recovery after traumatic brain injury in rat

    Directory of Open Access Journals (Sweden)

    Mohsen Marzban

    2010-01-01

    Full Text Available Introduction: This study was designed to investigate the effects of granulocyte colony-stimulating factor (G-CSF administration in rats for 6 weeks after traumatic brain injury (TBI. Methods: Adult male Wistar rats (n = 30 were injured with controlled cortical impact device and divided into four groups. The treatment groups (n = 10 each were injected subcutaneously with recombinant human G-CSF. Vehicle group (n=10 received phosphate buffered saline (PBS and only Brdu intraperitoneally. Bromodeoxyuridine (BrdU was used for mitotic labeling. Experimental rats were injected intraperitoneally with BrdU. Rats were killed at 6th week after traumatic brain injury. Neurological functional evaluation of animals was performed before and after injury using neurological severity scores (NSS. Animals were sacrificed 42 days after TBI and brain sections were stained using Brdu immunohistochemistry. Results: Statistically significant improvement in functional outcome was observed in treatment groups when compared with control (p<0.01. This benefit was visible 7 days after TBI and persisted until 42 days (end of trial. Histological analysis showed that Brdu cell positive was more in the lesion boundary zone at treatment animal group than all injected animals. Discussion: We believe that G-CSF therapeutic protocol reported here represents an attractive strategy for the development of a clinically significant noninvasive traumatic brain injury therapy.

  8. Primary and Secondary Vestibular Connections in the Brain Stem and Cerebellum: An Axoplasmic Transport Study in the Monkey and Cat

    Science.gov (United States)

    1983-08-25

    Edinger-Westphal nucleus in the cat, Brain Research, 141 (1978) 153-159. Lorente de No, R., Etudes sur le cerveau posterieur. Ill, Sur 1 es connexions...extra-cerebelleuses des fascicules afferents au cerveau , et sur la fontion de cet organe, Trav. Lab. Rech. Biol. Univ. Madrid, 22 (1924) 51-65

  9. Stem Cells

    Science.gov (United States)

    Stem cells are cells with the potential to develop into many different types of cells in the body. ... the body. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem ...

  10. Cochlear Implants

    Science.gov (United States)

    ... implant, including: • How long a person has been deaf, •The number of surviving auditory nerve fibers, and • ... Implant, Severe Sensoryneurial Hearing Loss Get Involved Professional Development Practice Management ENT Careers Marketplace Privacy Policy Terms ...

  11. Comparative effectiveness of ceramic-on-ceramic implants in stemmed hip replacement: a multinational study of six national and regional registries.

    Science.gov (United States)

    Sedrakyan, Art; Graves, Stephen; Bordini, Barbara; Pons, Miquel; Havelin, Leif; Mehle, Susan; Paxton, Elizabeth; Barber, Thomas; Cafri, Guy

    2014-12-17

    The rapid decline in use of conventional total hip replacement with a large femoral head size and a metal-on-metal bearing surface might lead to increased popularity of ceramic-on-ceramic bearings as another hard-on-hard alternative that allows implantation of a larger head. We sought to address comparative effectiveness of ceramic-on-ceramic and metal-on-HXLPE (highly cross-linked polyethylene) implants by utilizing the distributed health data network of the ICOR (International Consortium of Orthopaedic Registries), an unprecedented collaboration of national and regional registries and the U.S. FDA (Food and Drug Administration). A distributed health data network was developed by the ICOR and used in this study. The data from each registry are standardized and provided at a level of aggregation most suitable for the detailed analysis of interest. The data are combined across registries for comprehensive assessments. The ICOR coordinating center and study steering committee defined the inclusion criteria for this study as total hip arthroplasty performed without cement from 2001 to 2010 in patients forty-five to sixty-four years of age with osteoarthritis. Six national and regional registries (Kaiser Permanente and HealthEast in the U.S., Emilia-Romagna region in Italy, Catalan region in Spain, Norway, and Australia) participated in this study. Multivariate meta-analysis was performed with use of linear mixed models, with survival probability as the unit of analysis. We present the results of the fixed-effects model and include the results of the random-effects model in an appendix. SAS version 9.2 was used for all analyses. We first compared femoral head sizes of >28 mm and ≤28 mm within ceramic-on-ceramic implants and then compared ceramic-on-ceramic with metal-on-HXLPE. A total of 34,985 patients were included; 52% were female. We found a lower risk of revision associated with use of ceramic-on-ceramic implants when a larger head size was used (HR [hazard

  12. Stem cell therapies in preclinical models of stroke. Is the aged brain microenvironment refractory to cell therapy?

    Science.gov (United States)

    Sandu, Raluca Elena; Balseanu, Adrian Tudor; Bogdan, Catalin; Slevin, Mark; Petcu, Eugen; Popa-Wagner, Aurel

    2017-08-01

    Stroke is a devastating disease demanding vigorous search for new therapies. Initial enthusiasm to stimulate restorative processes in the ischemic brain by means of cell-based therapies has meanwhile converted into a more balanced view recognizing impediments that may be related to unfavorable age-associated environments. Recent results using a variety of drug, cell therapy or combination thereof suggest that, (i) treatment with Granulocyte-Colony Stimulating Factor (G-CSF) in aged rats has primarily a beneficial effect on functional outcome most likely via supportive cellular processes such as neurogenesis; (ii) the combination therapy, G-CSF with mesenchymal cells (G-CSF+BM-MSC or G-CSF+BM-MNC) did not further improve behavioral indices, neurogenesis or infarct volume as compared to G-CSF alone in aged animals; (iii) better results with regard to integration of transplanted cells in the aged rat environment have been obtained using iPS of human origin; (iv) mesenchymal cells may be used as drug carriers for the aged post-stroke brains. While the middle aged brain does not seem to impair drug and cell therapies, in a real clinical practice involving older post-stroke patients, successful regenerative therapies would have to be carried out for a much longer time. Copyright © 2017. Published by Elsevier Inc.

  13. The number of stem cells in the subependymal zone of the adult rodent brain is correlated with the number of ependymal cells and not with the volume of the niche.

    Science.gov (United States)

    Kazanis, Ilias; Ffrench-Constant, Charles

    2012-05-01

    The mammalian subependymal zone (SEZ; often called subventricular) situated at the lateral walls of the lateral ventricles of the brain contains a pool of relatively quiescent adult neural stem cells whose neurogenic activity persists throughout life. These stem cells are positioned in close proximity both to the ependymal cells that provide the cerebrospinal fluid interface and to the blood vessel endothelial cells, but the relative contribution of these 2 cell types to stem cell regulation remains undetermined. Here, we address this question by analyzing a naturally occurring example of volumetric scaling of the SEZ in a comparison of the mouse SEZ with the larger rat SEZ. Our analysis reveals that the number of stem cells in the SEZ niche is correlated with the number of ependymal cells rather than with the volume, thereby indicating the importance of ependymal-derived factors in the formation and function of the SEZ. The elucidation of the factors generated by ependymal cells that regulate stem cell numbers within the SEZ is, therefore, of importance for stem cell biology and regenerative neuroscience.

  14. 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

  15. The effect of cigarette smoke on fertilization and pre-implantation development: assessment using animal models, clinical data, and stem cells

    Directory of Open Access Journals (Sweden)

    Prue Talbot

    2011-01-01

    Full Text Available Numerous studies have repeatedly shown that women who smoke experience problems establishing and maintaining pregnancies, and recent work has further demonstrated that the in utero effects of smoke may not be manifested until months or even years after birth. The purpose of this review is to examine the recent literature dealing with the effects of cigarette smoke on the earliest stages of human prenatal development. Studies in this area have included the use of animal models, patients undergoing in vitro fertilization, and embryonic stem cell models. Events leading to fertilization, such as cumulus expansion, hyperactivation of sperm motility, and oocyte pick-up by the oviduct are all impaired by smoke exposure in animal models. Steps crucial to fertilization such as the acrosome reaction and sperm binding to the zona pellucida are likewise inhibited by cigarette smoke. Preimplantation embryos and stem cells that model embryos show a number of adverse responses to smoke exposure, including poor adhesion to extracellular matrices, diminished survival and proliferation, and increased apoptosis. The current literature demonstrates that the earliest stages of prenatal development are sensitive to smoke exposure and indicates that pregnant women should be advised not to smoke during this time.

  16. (3H)-dihydrotestosterone in catecholamine neurons of rat brain stem: combined localization by autoradiography and formaldehyde-induced fluorescence

    International Nuclear Information System (INIS)

    Heritage, A.S.; Stumpf, W.E.; Sar, M.; Grant, L.D.

    1981-01-01

    A combined formaldehyde-induced fluorescence (FIF)-autoradiography procedure was used to determine how and where the androgen, dihydrotestosterone (DHT), is associated with catecholamine systems in the rat brain. With this dual localization method, ( 3 H)-DHT target sites can be visualized in relation to catecholamine perikarya and terminals. In the hindbrain, catecholamine neurons adjacent to the fourth ventricle (group A4), the nucleus (n.) olivaris superior (group A5), the n. parabranchialis medialis (group A7), and in the locus coeruleus (group A6) and subcoeruleal regions, as well as in the substantia grisea centralis, concentrate ( 3 H)-DHT in their nuclei. ( 3 H)-DHT target neurons appear to be innervated by numerous catecholamine terminals in the following hindbrain regions: n. motorius dorsalis nervi vagi, n. tractus solitarii, n. commissuralis, n. raphe pallidus, n. olivaris inferior, the ventrolateral portion of the substantia grisea centralis, n. cuneiformis, and the ventrolateral reticular formation in the caudal mesencephalon. In the forebrain, ( 3 H)-DHT concentrates in nuclei of catecholamine neurons located in the n. arcuatus and n. periventricularis (group A12). In addition, ( 3 H)-DHT target neurons appear to be innervated by numerous catecholamine terminals in the following forebrain regions: n. periventricularis rotundocellularis, n. paraventricularis, n. dorsomedialis, n. periventricularis, area retrochiasmatica, n. interstititalis striae terminalis (ventral portion), and n. amygdaloideus centralis. The disclosure of a morphologic association between ( 3 H)-DHT target sites and certain brain catecholamine systems suggests a close functional interdependence between androgens and catecholamines

  17. [Influence of granulocyte colony stimulating factor on distribution of bone marrow stem cells and its role in protecting brain in rats with cerebral ischemia].

    Science.gov (United States)

    Li, Jian-sheng; Liu, Jing-xia; Liu, Ke; Wang, Ding-chao; Ren, Wei-hong; Zhang, Xin-feng; Tian, Yu-shou

    2011-06-01

    To explore the influence of recombination granulocyte colony stimulating factor (rG-CSF) on mobilization and distribution of bone marrow stem cells (BMSCs) in blood and brain tissue, and its role in protecting brain in rats with cerebral ischemia. One hundred and six Sprague-Dawley (SD) rats were divided into sham-operated group (n=10),model group (n=48), rG-CSF group (n=48) according to the method of random digital table, and rats in model and rG-CSF groups were divided into four subgroups: i.e. 2, 3, 7 and 14 days subgroups, with 12 rats in each subgroup. Middle cerebral artery occlusion (MCAO) model was reproduced with nylon thread. In rats of rG-CSF group rG-CSF (10 μg/kg) was administered by subcutaneous injection 3 days before and 2 days after operation respectively, once a day. Rats in sham-operated and model groups were administered with normal saline in the same volume, once a day. At the corresponding time after operation, general neural function score (GNFS) of rats was measured. Blood was collected through abdominal aorta, then white blood cell (WBC) and CD34+ cells in peripheral blood were counted. Brain pathologic changes were observed, and expression of CD34+ cells in rats brain tissue was determined by using immunohistochemical method. (1) GNFS was lower obviously in 2-day model group compared with that in sham-operated group, and then increased gradually. At 7 days and 14 days after operation, GNFS in rG-CSF group was higher significantly than that in model group (7 days: 11.86±0.69 vs. 10.53±0.76, 14 days: 13.38±0.52 vs. 12.38±0.52, both P<0.01). (2) WBC and CD34+ cells in peripheral blood in model group increased obviously, with the highest level appeared at 3 days and lowered at 7 days and 14 days. Increase of WBC and CD34+ cells in rats of rG-CSF group was more obvious than that of model group at each time point except CD34+ in 14 days group [WBC (×10(9)/L) 2 days: 11.75±1.76 vs. 8.07±1.27, 3 days: 13.07±1.70 vs. 10.88±1.78, 7 days: 8

  18. Retinoic acid-pretreated Wharton's jelly mesenchymal stem cells in combination with triiodothyronine improve expression of neurotrophic factors in the subventricular zone of the rat ischemic brain injury.

    Science.gov (United States)

    Sabbaghziarani, Fatemeh; Mortezaee, Keywan; Akbari, Mohammad; Kashani, Iraj Ragerdi; Soleimani, Mansooreh; Moini, Ashraf; Ataeinejad, Nahid; Zendedel, Adib; Hassanzadeh, Gholamreza

    2017-02-01

    Stroke is the consequence of limited blood flow to the brain with no established treatment to reduce the neurological deficits. Focusing on therapeutic protocols in targeting subventricular zone (SVZ) neurogenesis has been investigated recently. This study was designed to evaluate the effects of retinoic acid (RA)-pretreated Wharton's jelly mesenchymal stem cells (WJ-MSCs) in combination with triiodothyronine (T3) in the ischemia stroke model. Male Wistar rats were used to induce focal cerebral ischemia by middle cerebral artery occlusion (MCAO). There were seven groups of six animals: Sham, Ischemic, WJ-MSCs, RA-pretreated WJ-MSCs, T3, WJ-MSCs +T3, and RA-pretreated WJ-MSCs + T3. The treatment was performed at 24 h after ischemia, and animals were sacrificed one week later for assessments of retinoid X receptor β (RXRβ), brain-derived neurotrophic factor (BDNF), Sox2 and nestin in the SVZ. Pro-inflammatory cytokines in sera were measured at days four and seven after ischemia. RXRβ, BDNF, Sox2 and nestin had the significant expressions in gene and protein levels in the treatment groups, compared with the ischemic group, which were more vivid in the RA-pretreated WJ-MSCs + T3 (p ≤ 0.05). The same trend was also resulted for the levels of TNF-α and IL-6 at four days after ischemia (p ≤ 0.05). In conclusion, application of RA-pretreated WJ-MSCs + T3 could be beneficial in exerting better neurotrophic function probably via modulation of pro-inflammatory cytokines.

  19. A preclinical murine model for the early detection of radiation-induced brain injury using magnetic resonance imaging and behavioral tests for learning and memory: with applications for the evaluation of possible stem cell imaging agents and therapies.

    Science.gov (United States)

    Ngen, Ethel J; Wang, Lee; Gandhi, Nishant; Kato, Yoshinori; Armour, Michael; Zhu, Wenlian; Wong, John; Gabrielson, Kathleen L; Artemov, Dmitri

    2016-06-01

    Stem cell therapies are being developed for radiotherapy-induced brain injuries (RIBI). Magnetic resonance imaging (MRI) offers advantages for imaging transplanted stem cells. However, most MRI cell-tracking techniques employ superparamagnetic iron oxide particles (SPIOs), which are difficult to distinguish from hemorrhage. In current preclinical RIBI models, hemorrhage occurs concurrently with other injury markers. This makes the evaluation of the recruitment of transplanted SPIO-labeled stem cells to injury sites difficult. Here, we developed a RIBI model, with early injury markers reflective of hippocampal dysfunction, which can be detected noninvasively with MRI and behavioral tests. Lesions were generated by sub-hemispheric irradiation of mouse hippocampi with single X-ray beams of 80 Gy. Lesion formation was monitored with anatomical and contrast-enhanced MRI and changes in memory and learning were assessed with fear-conditioning tests. Early injury markers were detected 2 weeks after irradiation. These included an increase in the permeability of the blood-brain barrier, demonstrated by a 92 ± 20 % contrast enhancement of the irradiated versus the non-irradiated brain hemispheres, within 15 min of the administration of an MRI contrast agent. A change in short-term memory was also detected, as demonstrated by a 40.88 ± 5.03 % decrease in the freezing time measured during the short-term memory context test at this time point, compared to that before irradiation. SPIO-labeled stem cells transplanted contralateral to the lesion migrated toward the lesion at this time point. No hemorrhage was detected up to 10 weeks after irradiation. This model can be used to evaluate SPIO-based stem cell-tracking agents, short-term.

  20. In vitro modeling of experimental succinic semialdehyde dehydrogenase deficiency (SSADHD using brain-derived neural stem cells.

    Directory of Open Access Journals (Sweden)

    Kara R Vogel

    Full Text Available We explored the utility of neural stem cells (NSCs as an in vitro model for evaluating preclinical therapeutics in succinic semialdehyde dehydrogenase-deficient (SSADHD mice. NSCs were obtained from aldh5a1+/+ and aldh5a1-/- mice (aldh5a1 = aldehyde dehydrogenase 5a1 = SSADH. Multiple parameters were evaluated including: (1 production of GHB (γ-hydroxybutyrate, the biochemical hallmark of SSADHD; (2 rescue from cell death with the dual mTOR (mechanistic target of rapamycin inhibitor, XL-765, an agent previously shown to rescue aldh5a1-/- mice from premature lethality; (3 mitochondrial number, total reactive oxygen species, and mitochondrial superoxide production, all previously documented as abnormal in aldh5a1-/- mice; (4 total ATP levels and ATP consumption; and (5 selected gene expression profiles associated with epilepsy, a prominent feature in both experimental and human SSADHD. Patterns of dysfunction were observed in all of these parameters and mirrored earlier findings in aldh5a1-/- mice. Patterns of dysregulated gene expression between hypothalamus and NSCs centered on ion channels, GABAergic receptors, and inflammation, suggesting novel pathomechanisms as well as a developmental ontogeny for gene expression potentially associated with the murine epileptic phenotype. The NSC model of SSADHD will be valuable in providing a first-tier screen for centrally-acting therapeutics and prioritizing therapeutic concepts of preclinical animal studies applicable to SSADHD.