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Sample records for brain stem

  1. Similarity on neural stem cells and brain tumor stem cells in transgenic brain tumor mouse models

    Institute of Scientific and Technical Information of China (English)

    Guanqun Qiao; Qingquan Li; Gang Peng; Jun Ma; Hongwei Fan; Yingbin Li

    2013-01-01

    Although it is believed that glioma is derived from brain tumor stem cells, the source and molecular signal pathways of these cells are stil unclear. In this study, we used stable doxycycline-inducible transgenic mouse brain tumor models (c-myc+/SV40Tag+/Tet-on+) to explore the malignant trans-formation potential of neural stem cells by observing the differences of neural stem cel s and brain tumor stem cells in the tumor models. Results showed that chromosome instability occurred in brain tumor stem cells. The numbers of cytolysosomes and autophagosomes in brain tumor stem cells and induced neural stem cel s were lower and the proliferative activity was obviously stronger than that in normal neural stem cells. Normal neural stem cells could differentiate into glial fibril ary acidic protein-positive and microtubule associated protein-2-positive cells, which were also negative for nestin. However, glial fibril ary acidic protein/nestin, microtubule associated protein-2/nestin, and glial fibril ary acidic protein/microtubule associated protein-2 double-positive cells were found in induced neural stem cells and brain tumor stem cel s. Results indicate that induced neural stem cells are similar to brain tumor stem cells, and are possibly the source of brain tumor stem cells.

  2. Cerebral and brain stem Langerhans cell histiocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Breidahl, W.H. (Dept. of Radiology, Royal Perth Hospital, Nedlands (Australia)); Ives, F.J. (Dept. of Radiology, Royal Perth Hospital, Nedlands (Australia)); Khangure, M.S. (Dept. of Magnetic Resonance Imaging, Sir Charles Gairdner Hospital, Nedlands (Australia))

    1993-05-01

    Two patients with central nervous system manifestations of Langerhans cell histiocytosis, both with brain stem involvement, are reported. The onset of symptoms was at an age when the diagnosis might not have been considered. (orig.)

  3. 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

  4. Brain stem evoked response audiometry A Review

    OpenAIRE

    Balasubramanian Thiagarajan

    2015-01-01

    Brain stem evoked response audiometry (BERA) is a useful objective assessement of hearing. Major advantage of this procedure is its ability to test even infants in whom conventional audiometry may not be useful. This investigation can be used as a screening test for deafness in high risk infants. Early diagnosis and rehabilitation will reduce disability in these children. This article attempts to review the published literature on this subject. Methadology: Internet search using goog...

  5. Brain Cancer Stem Cells: Current Status on Glioblastoma Multiforme

    OpenAIRE

    2011-01-01

    Glioblastoma multiforme (GBM), an aggressive brain tumor of astrocytic/neural stem cell origin, represents one of the most incurable cancers. GBM tumors are highly heterogeneous. However, most tumors contain a subpopulation of cells that display neural stem cell characteristics in vitro and that can generate a new brain tumor upon transplantation in mice. Hence, previously identified molecular pathways regulating neural stem cell biology were found to represent the cornerstone of GBM stem cel...

  6. Stem Cells and the Origin and Propagation of Brain Tumors

    OpenAIRE

    2008-01-01

    In recent years there has been a flood of interest in the relationship between brain tumors and stem cells. Some investigators have focused on the sensitivity of normal stem cells to transformation, others have described phenotypic or functional similarities between tumor cells and stem cells, and still others have suggested that tumors contain a subpopulation of “cancer stem cells” that is crucial for tumor maintenance or propagation. While all these concepts are interesting and provide insi...

  7. Milrinone in Enterovirus 71 Brain Stem Encephalitis

    Science.gov (United States)

    Wang, Shih-Min

    2016-01-01

    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. PMID:27065870

  8. Milrinone in Enterovirus 71 Brain Stem Encephalitis

    Directory of Open Access Journals (Sweden)

    SHIH-MIN eWANG

    2016-03-01

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

  9. 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.

  10. 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.

  11. Mesenchymal Stem Cell Transplantation Attenuates Brain Injury After Neonatal Stroke

    NARCIS (Netherlands)

    van Velthoven, Cindy T. J.; Sheldon, R. Ann; Kavelaars, Annemieke; Derugin, Nikita; Vexler, Zinaida S.; Willemen, Hanneke L. D. M.; Maas, Mirjam; Heijnen, Cobi J.; Ferriero, Donna M.

    2013-01-01

    Background and Purpose-Brain injury caused by stroke is a frequent cause of perinatal morbidity and mortality with limited therapeutic options. Mesenchymal stem cells (MSC) have been shown to improve outcome after neonatal hypoxic-ischemic brain injury mainly by secretion of growth factors stimulati

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

    Science.gov (United States)

    Hong, Jin Ho; Lee, Ha Young; Lim, Myung Kwan; Kim, Mi Young; Kang, Young Hye; Lee, Kyung Hee; Cho, Soon Gu

    2013-01-01

    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.

  13. 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.

  14. 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.

  15. Drosophila neural stem cells in brain development and tumor formation.

    Science.gov (United States)

    Jiang, Yanrui; Reichert, Heinrich

    2014-01-01

    Neuroblasts, the neural stem cells in Drosophila, generate the complex neural structure of the central nervous system. Significant progress has been made in understanding the mechanisms regulating the self-renewal, proliferation, and differentiation in Drosophila neuroblast lineages. Deregulation of these mechanisms can lead to severe developmental defects and the formation of malignant brain tumors. Here, the authors review the molecular genetics of Drosophila neuroblasts and discuss some recent advances in stem cell and cancer biology using this model system.

  16. Brain stem auditory evoked responses in human infants and adults

    Science.gov (United States)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  17. Human Brain Stem Structures Respond Differentially to Noxious Heat

    Directory of Open Access Journals (Sweden)

    Alexander eRitter

    2013-09-01

    Full Text Available Concerning the physiological correlates of pain, the brain stem is considered to be one core region that is activated by noxious input. In animal studies, different slopes of skin heating (SSH with noxious heat led to activation in different columns of the midbrain periaqueductal grey (PAG. The present study aimed at finding a method for differentiating structures in PAG and other brain stem structures, which are associated with different qualities of pain in humans according to the structures that were associated with different behavioral significances to noxious thermal stimulation in animals. Brain activity was studied by fMRI in healthy subjects in response to steep and shallow SSH with noxious heat. We found differential activation to different SSH in the PAG and the rostral ventromedial medulla (RVM. In a second experiment we demonstrate that the different SSH were associated with different pain qualities. Our experiments provide evidence that brainstem structures, i.e. the PAG and the RVM, become differentially activated by different SSH. Therefore, different SSH can be utilized when brain stem structures are investigated and when it is aimed to activate these structures differentially. Moreover, percepts of first pain were elicited by shallow SSH whereas percepts of second pain were elicited by steep SSH. The stronger activation of these brain stem structures to SSH, eliciting percepts of second vs. first pain, might be of relevance for activating different coping strategies in response to the noxious input with the two types of SSH.

  18. Syrinx of the Spinal Cord and Brain Stem

    Science.gov (United States)

    ... Prompt Healthier Eating Scientists Working on Solar-Powered Prosthetic Limbs Health Highlights: March 23, 2017 Fruit Juice for Kids: A Serving a Day OK ALL NEWS > Resources ... may extend downward to affect the entire cord. Syrinxes that extend into or begin in the lower part of the brain stem may compress pathways ...

  19. 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...

  20. Growth hormone (GH), brain development and neural stem cells.

    Science.gov (United States)

    Waters, M J; Blackmore, D G

    2011-12-01

    A range of observations support a role for GH in development and function of the brain. These include altered brain structure in GH receptor null mice, and impaired cognition in GH deficient rodents and in a subgroup of GH receptor defective patients (Laron dwarfs). GH has been shown to alter neurogenesis, myelin synthesis and dendritic branching, and both the GH receptor and GH itself are expressed widely in the brain. We have found a population of neural stem cells which are activated by GH infusion, and which give rise to neurons in mice. These stem cells are activated by voluntary exercise in a GH-dependent manner. Given the findings that local synthesis of GH occurs in the hippocampus in response to a memory task, and that GH replacement improves memory and cognition in rodents and humans, these new observations warrant a reappraisal of the clinical importance of GH replacement in GH deficient states.

  1. Mesenchymal Stem Cells in the Treatment of Traumatic Brain Injury

    Science.gov (United States)

    Hasan, Anwarul; Deeb, George; Rahal, Rahaf; Atwi, Khairallah; Mondello, Stefania; Marei, Hany Elsayed; Gali, Amr; Sleiman, Eliana

    2017-01-01

    Traumatic brain injury (TBI) is characterized by a disruption in the normal function of the brain due to an injury following a trauma, which can potentially cause severe physical, cognitive, and emotional impairment. The primary insult to the brain initiates secondary injury cascades consisting of multiple complex biochemical responses of the brain that significantly influence the overall severity of the brain damage and clinical sequelae. The use of mesenchymal stem cells (MSCs) offers huge potential for application in the treatment of TBI. MSCs have immunosuppressive properties that reduce inflammation in injured tissue. As such, they could be used to modulate the secondary mechanisms of injury and halt the progression of the secondary insult in the brain after injury. Particularly, MSCs are capable of secreting growth factors that facilitate the regrowth of neurons in the brain. The relative abundance of harvest sources of MSCs also makes them particularly appealing. Recently, numerous studies have investigated the effects of infusion of MSCs into animal models of TBI. The results have shown significant improvement in the motor function of the damaged brain tissues. In this review, we summarize the recent advances in the application of MSCs in the treatment of TBI. The review starts with a brief introduction of the pathophysiology of TBI, followed by the biology of MSCs, and the application of MSCs in TBI treatment. The challenges associated with the application of MSCs in the treatment of TBI and strategies to address those challenges in the future have also been discussed.

  2. 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...

  3. Stem cell-paved biobridges facilitate stem transplant and host brain cell interactions for stroke therapy.

    Science.gov (United States)

    Duncan, Kelsey; Gonzales-Portillo, Gabriel S; Acosta, Sandra A; Kaneko, Yuji; Borlongan, Cesar V; Tajiri, Naoki

    2015-10-14

    Distinguished by an infarct core encased within a penumbra, stroke remains a primary source of mortality within the United States. While our scientific knowledge regarding the pathology of stroke continues to improve, clinical treatment options for patients suffering from stroke are extremely limited. Tissue plasminogen activator (tPA) remains the sole FDA-approved drug proven to be helpful following stroke. However, due to the need to administer the drug within 4.5h of stroke onset its usefulness is constrained to less than 5% of all patients suffering from ischemic stroke. One experimental therapy for the treatment of stroke involves the utilization of stem cells. Stem cell transplantation has been linked to therapeutic benefit by means of cell replacement and release of growth factors; however the precise means by which this is accomplished has not yet been clearly delineated. Using a traumatic brain injury model, we recently demonstrated the ability of transplanted mesenchymal stromal cells (MSCs) to form a biobridge connecting the area of injury to the neurogenic niche within the brain. We hypothesize that MSCs may also have the capacity to create a similar biobridge following stroke; thereby forming a conduit between the neurogenic niche and the stroke core and peri-infarct area. We propose that this biobridge could assist and promote interaction of host brain cells with transplanted stem cells and offer more opportunities to enhance the effectiveness of stem cell therapy in stroke. This article is part of a Special Issue entitled SI: Cell Interactions In Stroke.

  4. Rescue of Brain Function Using Tunneling Nanotubes Between Neural Stem Cells and Brain Microvascular Endothelial Cells.

    Science.gov (United States)

    Wang, Xiaoqing; Yu, Xiaowen; Xie, Chong; Tan, Zijian; Tian, Qi; Zhu, Desheng; Liu, Mingyuan; Guan, Yangtai

    2016-05-01

    Evidence indicates that neural stem cells (NSCs) can ameliorate cerebral ischemia in animal models. In this study, we investigated the mechanism underlying one of the neuroprotective effects of NSCs: tunneling nanotube (TNT) formation. We addressed whether the control of cell-to-cell communication processes between NSCs and brain microvascular endothelial cells (BMECs) and, particularly, the control of TNT formation could influence the rescue function of stem cells. In an attempt to mimic the cellular microenvironment in vitro, a co-culture system consisting of terminally differentiated BMECs from mice in a distressed state and NSCs was constructed. Additionally, engraftment experiments with infarcted mouse brains revealed that control of TNT formation influenced the effects of stem cell transplantation in vivo. In conclusion, our findings provide the first evidence that TNTs exist between NSCs and BMECs and that regulation of TNT formation alters cell function.

  5. 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.

  6. Correlation between heat shock protein 70 expression in the brain stem and sudden death after experimental traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    ZHAO Lian-xu; XU Xiao-hu; LIU Chao; PAN Su-yue; ZHU Jia-zhen; ZHANG Cheng

    2001-01-01

    Objective: The aim of this study was to determine the patterns of heat-shock protein 70 (HSP70) biosynthesis following traumatic brain injury, and observe the effect of HSP70 induction on the function of the vital center in the brain stem. Methods: Rat models of sudden death resulted form traumatic brain injury were produced, and HSP70 expression in the rat brain stem was determined by immunohistochemistry, the induction of HSP70 mRNA detected by RT-PCR. Results: The level of HSP70 mRNA was prominently elevated in the brain stem as early as 1 5 min following the impact injury, while HSP70 expression was only observed 3 to 6 h after the injury. It was also observed that the levels of HSP70 mRNA but not the protein were elevated in the brain stem of sudden death rats. Conclusion: The synthesis of HSP70 was significantly enhanced in the brain stem following traumatic injury, and the expression of HSP70 is beneficial to eliminate the stress agents, and to sustain the cellular protein homeostasis. When the injury disturbs the synthesis of HSP70 to disarm the protective mechanism of heat-shock proteins, dysfunction of the vital center in the brain stem, and consequently death may occur. Breach in the synchronization of HSP70 mRNA-protein can be indicative of fatal damage to the nerve cells.

  7. A case of a brain stem abscess with a favorable outcome

    NARCIS (Netherlands)

    Bulthuis, Vincent J; Gubler, Felix S; Teernstra, Onno P M; Temel, Yasin

    2015-01-01

    BACKGROUND: A brain stem abscess is a rare and severe medical condition. Here, we present a rare case of a brain stem abscess in a young pregnant woman, requiring acute stereotactic intervention. CASE DESCRIPTION: A 36-year-old woman presented with a headache, nausea, and vomiting, and computed tomo

  8. Transplantation of autologous bone marrow-derived mesenchymal stem cells for traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Jindou Jiang; Xingyao Bu; Meng Liu; Peixun Cheng

    2012-01-01

    Results from the present study demonstrated that transplantation of autologous bone marrow-derived mesenchymal stem cells into the lesion site in rat brain significantly ameliorated brain tissue pathological changes and brain edema, attenuated glial cell proliferation, and increased brain-derived neurotrophic factor expression. In addition, the number of cells double-labeled for 5-bromodeoxyuridine/glial fibrillary acidic protein and cells expressing nestin increased. Finally, blood vessels were newly generated, and the rats exhibited improved motor and cognitive functions. These results suggested that transplantation of autologous bone marrow-derived mesenchymal stem cells promoted brain remodeling and improved neurological functions following traumatic brain injury.

  9. Neural activity control of neural stem cells and SVZ niche response to brain injury

    OpenAIRE

    Páez González, Patricia

    2014-01-01

    Patricia Paez-Gonzalez Kuo Lab, Dept. of Cell Biology, Duke University Medical Center, NC,USA. Date: 11/16/2014 Utilizing stem cells in the adult brain hold great promise for regenerative medicine. Harnessing ability of adult neural stem cells (NSCs) to generate new neurons or other types of brain cells may provide much needed therapies for patients suffering from brain injuries or neuro-degenerative diseases such as Parkinson’s, Scizophrenia, or Alzheimer’s disease. However...

  10. Prospects and Limitations of Using Endogenous Neural Stem Cells for Brain Regeneration

    OpenAIRE

    Kazunobu Sawamoto; Eisuke Kako; Naoko Kaneko

    2011-01-01

    Neural stem cells (NSCs) are capable of producing a variety of neural cell types, and are indispensable for the development of the mammalian brain. NSCs can be induced in vitro from pluripotent stem cells, including embryonic stem cells and induced-pluripotent stem cells. Although the transplantation of these exogenous NSCs is a potential strategy for improving presently untreatable neurological conditions, there are several obstacles to its implementation, including tumorigenic, immunologica...

  11. Objective evaluation of fourth ventricle displacement in brain CT findings. 4 cases of brain stem tumor

    Energy Technology Data Exchange (ETDEWEB)

    Okino, Fumiko; Eguchi, Tsuyako; Shinohara, Teruo; Hatano, Mitsunori (Yamaguchi Univ., Ube (Japan). School of Medicine)

    1983-11-01

    Distance between the ridge of the sella turcica and the anterior wall of the fourth ventricle (a) and the distance between the ridge of the sella and the posterior pole in the occipital region (b) were measured on the slice visualizing the fourth ventricle and sella. The location of the fourth ventricle was expressed by a/b, and its normal value was calculated for comparison with that in a patient group. The a/b values of the control group were in the range of 0.33 and 0.48 with a mean +- SD of 0.41+-0.3 and was not subject to the influences of age, sex distinction, cranial shape or slicing direction. The a/b values of the patient group were all abnormal (more than mean +- 2SD of the control group) on initial CT and showed an increase with progress of the disease activity. Measurement of the a/b on brain CT was thought to serve as a useful indicator for early detection and follow-up of the course of lesions occupying the brain stem (especially brain stem tumors).

  12. Hypoxic-ischemic encephalopathy with cystic brain stem necroses and thalamic calcifications in a preterm twin.

    Science.gov (United States)

    Peters, B; Walka, M M; Friedmann, W; Stoltenburg-Didinger, G; Obladen, M

    2000-06-01

    A severe and rare ischemic brain lesion in a preterm twin boy is reported. The boy was born after two weeks of anhydramnios and amnionic infection at 24 weeks of gestation. Following a difficult Caesarean section and prolonged umbilical cord compression he developed prenatal acidosis with an umbilical cord pH of 6.96. At the age of 7 h, heart rate variability narrowed due to severely disturbed brain stem function and the patient developed clinical signs of hypoxic-ischemic encephalopathy. Sonography demonstrated extensive symmetrical brain stem and basal ganglia lesions. After a prolonged comatose and apneic state, death occurred at the age of 25 days. Autopsy confirmed columnar bilateral cavitation of basal ganglia, diencephalon, brain stem and spinal gray matter, as well as focal calcifications in the palladium, thalamus, and brain stem. The findings highly resemble those observed after experimental or clinical cardiac arrest.

  13. Biological effect of velvet antler polypeptides on neural stem cells from embryonic rat brain

    Institute of Scientific and Technical Information of China (English)

    LU Lai-jin; CHEN Lei; MENG Xiao-ting; YANG Fan; ZHANG Zhi-xin; CHEN Dong

    2005-01-01

    Background Velvet antler polypeptides (VAPs), which are derived from the antler velvets, have been reported to maintain survival and promote growth and differentiation of neural cells and, especially the development of neural tissues. This study was designed to explore the influence of VAPs on neural stem cells in vitro derived from embryonic rat brain. Methods Neural stem cells derived from E12-14 rat brain were isolated, cultured, and expanded for 7 days until neural stem cell aggregations and neurospheres were generated. The neurospheres were cultured under the condition of different concentration of VAPs followed by immunocytochemistry to detect the differentiation of neural stem cells. Results VAPs could remarkablely promote differentiation of neural stem cells and most neural stem cells were induced to differentiate towards the direction of neurons under certain concentration of VAPs.Conclusion Neural stem cells can be successfully induced into neurons by VAPs in vitro, which could provide a basis for regeneration of the nervous system.

  14. Neurodevelopment. Live imaging of adult neural stem cell behavior in the intact and injured zebrafish brain.

    Science.gov (United States)

    Barbosa, Joana S; Sanchez-Gonzalez, Rosario; Di Giaimo, Rossella; Baumgart, Emily Violette; Theis, Fabian J; Götz, Magdalena; Ninkovic, Jovica

    2015-05-15

    Adult neural stem cells are the source for restoring injured brain tissue. We used repetitive imaging to follow single stem cells in the intact and injured adult zebrafish telencephalon in vivo and found that neurons are generated by both direct conversions of stem cells into postmitotic neurons and via intermediate progenitors amplifying the neuronal output. We observed an imbalance of direct conversion consuming the stem cells and asymmetric and symmetric self-renewing divisions, leading to depletion of stem cells over time. After brain injury, neuronal progenitors are recruited to the injury site. These progenitors are generated by symmetric divisions that deplete the pool of stem cells, a mode of neurogenesis absent in the intact telencephalon. Our analysis revealed changes in the behavior of stem cells underlying generation of additional neurons during regeneration.

  15. Breaking the Blood-Brain Barrier With Mannitol to Aid Stem Cell Therapeutics in the Chronic Stroke Brain.

    Science.gov (United States)

    Tajiri, Naoki; Lee, Jea Young; Acosta, Sandra; Sanberg, Paul R; Borlongan, Cesar V

    2016-01-01

    Blood-brain barrier (BBB) permeabilizers, such as mannitol, can facilitate peripherally delivered stem cells to exert therapeutic benefits on the stroke brain. Although this BBB permeation-aided stem cell therapy has been demonstrated in the acute stage of stroke, such BBB permeation in the chronic stage of the disease remains to be examined. Adult Sprague-Dawley rats initially received sham surgery or experimental stroke via the 1-h middle cerebral artery occlusion (MCAo) model. At 1 month after the MCAo surgery, stroke animals were randomly assigned to receive human umbilical cord stem cells only (2 million viable cells), mannitol only (1.1 mol/L mannitol at 4°C), combined human umbilical cord stem cells (200,000 viable cells) and mannitol (1.1 mol/L mannitol at 4°C), and vehicle (phosphate-buffered saline) only. Stroke animals that received human umbilical cord blood cells alone or combined human umbilical cord stem cells and mannitol exhibited significantly improved motor performance and significantly better brain cell survival in the peri-infarct area compared to stroke animals that received vehicle or mannitol alone, with mannitol treatment reducing the stem cell dose necessary to afford functional outcomes. Enhanced neurogenesis in the subventricular zone accompanied the combined treatment of human umbilical cord stem cells and mannitol. We showed that BBB permeation facilitates the therapeutic effects of a low dose of peripherally transplanted stem cells to effectively cause functional improvement and increase neurogenesis in chronic stroke.

  16. NFL-lipid nanocapsules for brain neural stem cell targeting in vitro and in vivo.

    Science.gov (United States)

    Carradori, Dario; Saulnier, Patrick; Préat, Véronique; des Rieux, Anne; Eyer, Joel

    2016-09-28

    The replacement of injured neurons by the selective stimulation of neural stem cells in situ represents a potential therapeutic strategy for the treatment of neurodegenerative diseases. The peptide NFL-TBS.40-63 showed specific interactions towards neural stem cells of the subventricular zone. The aim of our work was to produce a NFL-based drug delivery system able to target neural stem cells through the selective affinity between the peptide and these cells. NFL-TBS.40-63 (NFL) was adsorbed on lipid nanocapsules (LNC) whom targeting efficiency was evaluated on neural stem cells from the subventricular zone (brain) and from the central canal (spinal cord). NFL-LNC were incubated with primary neural stem cells in vitro or injected in vivo in adult rat brain (right lateral ventricle) or spinal cord (T10). NFL-LNC interactions with neural stem cells were different depending on the origin of the cells. NFL-LNC showed a preferential uptake by neural stem cells from the brain, while they did not interact with neural stem cells from the spinal cord. The results obtained in vivo correlate with the results observed in vitro, demonstrating that NFL-LNC represent a promising therapeutic strategy to selectively deliver bioactive molecules to brain neural stem cells.

  17. Electro-Acupuncture for Treatment of Dysequillibrium Due to Cerebellum or Brain Stem Infarction

    Institute of Scientific and Technical Information of China (English)

    赵宏; 刘志顺; 刘效娟

    2003-01-01

    @@ The authors treated 26 cases of dysequillibrium due tocerebellum or brain stem infarction byelectro-acupuncture from Aug 2000 - April 2002. Theresults were quite satisfactory and reported as follows.

  18. Schwann Cells Transplantation Promoted and the Repair of Brain Stem Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    HONG WAN; YI-HUA AN; MEI-ZHEN SUN; YA-ZHUO ZHANG; ZHONG-CHENG WANG

    2003-01-01

    To explore the possibility of Schwann cells transplantation to promote the repair of injured brain stem reticular structure in rats. Methods Schwann cells originated from sciatic nerves of 1 to 2-day-old rats were expanded and labelled by BrdU in vitro, transplanted into rat brain stem reticular structure that was pre-injured by electric needle stimulus. Immunohistochemistry and myelin-staining were used to investigate the expression of BrdU, GAP-43 and new myelination respectively. Results BrdU positive cells could be identified for up to 8 months and their number increased by about 23%, which mainly migrated toward injured ipsilateral cortex. The GAP-43expression reached its peak in 1 month after transplantation and was significantly higher than that in the control group. New myelination could be seen in destructed brain stem areas. Conclusion The transplantation of Schwann cells can promote the restoration of injured brain stem reticular structure.

  19. Recruited brain tumor-derived mesenchymal stem cells contribute to brain tumor progression.

    Science.gov (United States)

    Behnan, Jinan; Isakson, Pauline; Joel, Mrinal; Cilio, Corrado; Langmoen, Iver A; Vik-Mo, Einar O; Badn, Wiaam

    2014-05-01

    The identity of the cells that contribute to brain tumor structure and progression remains unclear. Mesenchymal stem cells (MSCs) have recently been isolated from normal mouse brain. Here, we report the infiltration of MSC-like cells into the GL261 murine glioma model. These brain tumor-derived mesenchymal stem cells (BT-MSCs) are defined with the phenotype (Lin-Sca-1+CD9+CD44+CD166+/-) and have multipotent differentiation capacity. We show that the infiltration of BT-MSCs correlates to tumor progression; furthermore, BT-MSCs increased the proliferation rate of GL261 cells in vitro. For the first time, we report that the majority of GL261 cells expressed mesenchymal phenotype under both adherent and sphere culture conditions in vitro and that the non-MSC population is nontumorigenic in vivo. Although the GL261 cell line expressed mesenchymal phenotype markers in vitro, most BT-MSCs are recruited cells from host origin in both wild-type GL261 inoculated into green fluorescent protein (GFP)-transgenic mice and GL261-GFP cells inoculated into wild-type mice. We show the expression of chemokine receptors CXCR4 and CXCR6 on different recruited cell populations. In vivo, the GL261 cells change marker profile and acquire a phenotype that is more similar to cells growing in sphere culture conditions. Finally, we identify a BT-MSC population in human glioblastoma that is CD44+CD9+CD166+ both in freshly isolated and culture-expanded cells. Our data indicate that cells with MSC-like phenotype infiltrate into the tumor stroma and play an important role in tumor cell growth in vitro and in vivo. Thus, we suggest that targeting BT-MSCs could be a possible strategy for treating glioblastoma patients.

  20. Possible role of brain stem respiratory neurons in mediating vomiting during space motion sickness

    Science.gov (United States)

    Miller, A. D.; Tan, L. K.

    1987-01-01

    The object of this study was to determine if brain stem expiratory neurons control abdominal muscle activity during vomiting. The activity of 27 ventral respiratory group expiratory neurons, which are known to be of primary importance for control of abdominal muscle activity during respiration, was recorded. It is concluded that abdominal muscle activity during vomiting must be controlled not only by some brain stem expiratory neurons but also by other input(s).

  1. The BRAIN Initiative Provides a Unifying Context for Integrating Core STEM Competencies into a Neurobiology Course.

    Science.gov (United States)

    Schaefer, Jennifer E

    2016-01-01

    The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative introduced by the Obama Administration in 2013 presents a context for integrating many STEM competencies into undergraduate neuroscience coursework. The BRAIN Initiative core principles overlap with core STEM competencies identified by the AAAS Vision and Change report and other entities. This neurobiology course utilizes the BRAIN Initiative to serve as the unifying theme that facilitates a primary emphasis on student competencies such as scientific process, scientific communication, and societal relevance while teaching foundational neurobiological content such as brain anatomy, cellular neurophysiology, and activity modulation. Student feedback indicates that the BRAIN Initiative is an engaging and instructional context for this course. Course module organization, suitable BRAIN Initiative commentary literature, sample primary literature, and important assignments are presented.

  2. Are human dental papilla-derived stem cell and human brain-derived neural stem cell transplantations suitable for treatment of Parkinson's disease?

    Institute of Scientific and Technical Information of China (English)

    Hyung Ho Yoon; Joongkee Min; Nari Shin; Yong Hwan Kim; Jin-Mo Kim; Yu-Shik Hwang; Jun-Kyo Francis Suh; Onyou Hwang; Sang Ryong Jeon

    2013-01-01

    Transplantation of neural stem cells has been reported as a possible approach for replacing impaired dopaminergic neurons. In this study, we tested the efficacy of early-stage human dental papilla-derived stem cells and human brain-derived neural stem cells in rat models of 6-hydroxydopamine-induced Parkinson's disease. Rats received a unilateral injection of 6-hydroxydopamine into right medial forebrain bundle, followed 3 weeks later by injections of PBS, early-stage human dental papilla-derived stem cells, or human brain-derived neural stem cells into the ipsilateral striatum. All of the rats in the human dental papilla-derived stem cell group died from tumor formation at around 2 weeks following cell transplantation. Postmortem examinations revealed homogeneous malignant tumors in the striatum of the human dental papilla-derived stem cell group. Stepping tests revealed that human brain-derived neural stem cell transplantation did not improve motor dysfunction. In apomorphine-induced rotation tests, neither the human brain-derived neural stem cell group nor the control groups (PBS injection) demonstrated significant changes. Glucose metabolism in the lesioned side of striatum was reduced by human brain-derived neural stem cell transplantation. [18 F]-FP-CIT PET scans in the striatum did not demonstrate a significant increase in the human brain-derived neural stem cell group. Tyrosine hydroxylase (dopaminergic neuronal marker) staining and G protein-activated inward rectifier potassium channel 2 (A9 dopaminergic neuronal marker) were positive in the lesioned side of striatum in the human brain-derived neural stem cell group. The use of early-stage human dental papilla-derived stem cells confirmed its tendency to form tumors. Human brain-derived neural stem cells could be partially differentiated into dopaminergic neurons, but they did not secrete dopamine.

  3. Isolation, cultivation and identification of brain glioma stem cells by magnetic bead sorting

    Institute of Scientific and Technical Information of China (English)

    Xiuping Zhou; Chao Zheng; Qiong Shi; Xiang Li; Zhigang Shen; Rutong Yu

    2012-01-01

    This study describes a detailed process for obtaining brain glioma stem cells from freshly dissected human brain glioma samples using an immunomagnetic bead technique combined with serum-free media pressure screening. Furthermore, the proliferation, differentiation and self-renewal biological features of brain glioma stem cells were identified. Results showed that a small number of CD133 positive tumor cells isolated from brain glioma samples survived as a cell suspension in serum-free media and proliferated. Subcultured CD133 positive cells maintained a potent self-renewal and proliferative ability, and expressed the stem cell-specific markers CD133 and nestin. After incubation with fetal bovine serum, the number of glial fibrillary acidic protein and microtubule associated protein 2 positive cells increased significantly, indicating that the cultured brain glioma stem cells can differentiate into astrocytes and neurons. Western blot analysis showed that tumor suppressor phosphatase and tensin homolog was highly expressed in tumor spheres compared with the differentiated tumor cells. These experimental findings indicate that the immunomagnetic beads technique is a useful method to obtain brain glioma stem cells from human brain tumors.

  4. 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.

  5. Stem cells modified by brain-derived neurotrophic fac-tor to promote stem cells differentiation into neurons and enhance neuromotor function after brain injury

    Institute of Scientific and Technical Information of China (English)

    ZHANG Sai; LIU Xiao-zhi; LIU Zhen-lin; WANG Yan-min; HU Qun-liang; MA Tie-zhu; SUN Shi-zhong

    2009-01-01

    Objective: To promote stem cells differentiation into neurons and enhance neuromotor function after brain in-jury through brain-derived neurotrophic factor (BDNF) induction.Methods: Recombinant adenovirus vector was ap-plied to the transfection of BDNF into human-derived um-bilical cord mesenchymal stem cells (UCMSCs). Enzyme linked immunosorbent assay (ELISA) was used to deter-mine the secretion phase of BDNF. The brain injury model of athymic mice induced by hydraulic pressure percussion was established for transplantation of stem cells into the edge of injury site. Nerve function scores were obtained, and the expression level of transfected and non-transfected BDNF, proportion of neuron specific enolase (NSE) andglial fibrillary acidic protein (GFAP), and the number of apoptosis cells were compared respectively. Results: The BDNF expression achieved its stabiliza-tion at a high level 72 hours after gene transfection. The mouse obtained a better score of nerve function, and the proportion of the NSE-positive cells increased significantly (P<0.05), but GFAP-positive cells decreased in BDNF-UCMSCs group compared with the other two groups (P<0.05). At the site of high expression of BDNF, the number of apoptosis cells decreased markedly.Conclusion: BDNF gene can promote the differentia-tion of the stem cells into neurons rather than gliai cells, and enhance neuromotor function after brain injury.

  6. Prospects and Limitations of Using Endogenous Neural Stem Cells for Brain Regeneration

    Directory of Open Access Journals (Sweden)

    Kazunobu Sawamoto

    2011-01-01

    Full Text Available Neural stem cells (NSCs are capable of producing a variety of neural cell types, and are indispensable for the development of the mammalian brain. NSCs can be induced in vitro from pluripotent stem cells, including embryonic stem cells and induced-pluripotent stem cells. Although the transplantation of these exogenous NSCs is a potential strategy for improving presently untreatable neurological conditions, there are several obstacles to its implementation, including tumorigenic, immunological, and ethical problems. Recent studies have revealed that NSCs also reside in the adult brain. The endogenous NSCs are activated in response to disease or trauma, and produce new neurons and glia, suggesting they have the potential to regenerate damaged brain tissue while avoiding the above-mentioned problems. Here we present an overview of the possibility and limitations of using endogenous NSCs in regenerative medicine.

  7. Prospects and limitations of using endogenous neural stem cells for brain regeneration.

    Science.gov (United States)

    Kaneko, Naoko; Kako, Eisuke; Sawamoto, Kazunobu

    2011-01-14

    Neural stem cells (NSCs) are capable of producing a variety of neural cell types, and are indispensable for the development of the mammalian brain. NSCs can be induced in vitro from pluripotent stem cells, including embryonic stem cells and induced-pluripotent stem cells. Although the transplantation of these exogenous NSCs is a potential strategy for improving presently untreatable neurological conditions, there are several obstacles to its implementation, including tumorigenic, immunological, and ethical problems. Recent studies have revealed that NSCs also reside in the adult brain. The endogenous NSCs are activated in response to disease or trauma, and produce new neurons and glia, suggesting they have the potential to regenerate damaged brain tissue while avoiding the above-mentioned problems. Here we present an overview of the possibility and limitations of using endogenous NSCs in regenerative medicine.

  8. Origins and clinical implications of the brain tumor stem cell hypothesis

    OpenAIRE

    2009-01-01

    With the advent of the cancer stem cell hypothesis, the field of cancer research has experienced a revolution in how we think of and approach cancer. The discovery of “brain tumor stem cells” has offered an explanation for several long-standing conundrums on why brain tumors behave the way they do to treatment. Despite the great amount of research that has been done in order to understand the molecular aspects of malignant gliomas, the prognosis of brain tumors remains dismal. The slow progre...

  9. 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.

  10. Expression of c-jun in brain stem following moderate lateral fluid percussion brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the expression of c-jun in brain stem following moderate lateral fluid percussion brain injury in rats, and to observe the temporal patterns of its expressions following percussion.METHODS: Male Sprague-Dawley rats were divided into normal control, sham operation control and injury groups. The rats of injury group subjected to moderate lateral fluid percussion injury (0.2 mPa), and then were subdivided into 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h and 12 h groups according to the time elapsed after injury. The expression of c-jun was studied by immunohistochemistry and in situ hybridization. RESULTS: After percussion for 15 min, Jun positive neurons increased in brain stem progressively, and peaked at 12h. At 5min after percussion, the induction of c-jun mRNA was increased, and remained elevated up to 1h-2h after brain injury. CONCLUSION: The induction and expression of the c-jun in brain stem after fluid percussion brain injury were increased rapidly and lasted for a long time.

  11. PPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation.

    Science.gov (United States)

    Trapp, Stefan; Cork, Simon C

    2015-10-15

    Within the brain, glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Additionally, GLP-1 influences the mesolimbic reward system to modulate the rewarding properties of palatable food. GLP-1 is produced in the gut and by hindbrain preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarii (NTS) and medullary intermediate reticular nucleus. Transgenic mice expressing glucagon promoter-driven yellow fluorescent protein revealed that PPG neurons not only project to central autonomic control regions and mesolimbic reward centers, but also strongly innervate spinal autonomic neurons. Therefore, these brain stem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to sympathetic preganglionic neurons. Electrical recordings from PPG neurons in vitro have revealed that they receive synaptic inputs from vagal afferents entering via the solitary tract. Vagal afferents convey satiation to the brain from signals like postprandial gastric distention or activation of peripheral GLP-1 receptors. CCK and leptin, short- and long-term satiety peptides, respectively, increased the electrical activity of PPG neurons, while ghrelin, an orexigenic peptide, had no effect. These findings indicate that satiation is a main driver of PPG neuronal activation. They also show that PPG neurons are in a prime position to respond to both immediate and long-term indicators of energy and feeding status, enabling regulation of both energy balance and general autonomic homeostasis. This review discusses the question of whether PPG neurons, rather than gut-derived GLP-1, are providing the physiological substrate for the effects elicited by central nervous system GLP-1 receptor activation.

  12. The preventive effects of neural stem cells and mesenchymal stem cells intra-ventricular injection on brain stroke in rats

    Directory of Open Access Journals (Sweden)

    Seyed Mojtaba Hosseini

    2015-01-01

    Full Text Available Introduction: Stroke is one of the most important causes of disability in developed countries and, unfortunately, there is no effective treatment for this major problem of central nervous system (CNS; cell therapy may be helpful to recover this disease. In some conditions such as cardiac surgeries and neurosurgeries, there are some possibilities of happening brain stroke. Inflammation of CNS plays an important role in stroke pathogenesis, in addition, apoptosis and neural death could be the other reasons of poor neurological out come after stroke. In this study, we examined the preventive effects of the neural stem cells (NSCs and mesenchymal stem cells (MSCs intra-ventricular injected on stroke in rats. Aim: The aim of this study was to investigate the preventive effects of neural and MSCs for stroke in rats. Materials and Methods: The MSCs were isolated by flashing the femurs and tibias of the male rats with appropriate media. The NSCs were isolated from rat embryo ganglion eminence and they cultured NSCs media till the neurospheres formed. Both NSCs and MSCs were labeled with PKH26-GL. One day before stroke, the cells were injected into lateral ventricle stereotactically. Results: During following for 28 days, the neurological scores indicated that there are better recoveries in the groups received stem cells and they had less lesion volume in their brain measured by hematoxylin and eosin staining. Furthermore, the activities of caspase-3 were lower in the stem cell received groups than control group and the florescent microscopy images showed that the stem cells migrated to various zones of the brains. Conclusion: Both NSCs and MSCs are capable of protecting the CNS against ischemia and they may be good ways to prevent brain stroke consequences situations.

  13. Stem cell therapy for neonatal brain injury : Perspectives and Challenges

    NARCIS (Netherlands)

    Titomanlio, Luigi; Kavelaars, Annemieke; Dalous, Jeremie; Mani, Shyamala; El Ghouzzi, Vincent; Heijnen, Cobi; Baud, Olivier; Gressens, Pierre

    2011-01-01

    Cerebral palsy is a major health problem caused by brain damage during pregnancy, delivery, or the immediate postnatal period. Perinatal stroke, intraventricular hemorrhage, and asphyxia are the most common causes of neonatal brain damage. Periventricular white matter damage (periventricular leukoma

  14. [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.

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

    Directory of Open Access Journals (Sweden)

    Julie Y H Chan

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS

  16. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Fatemeh Anbari; Mohammad Ali Khalili; Ahmad Reza Bahrami; Arezoo Khoradmehr; Fatemeh Sadeghian; Farzaneh Fesahat; Ali Nabi

    2014-01-01

    To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intrave-nous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and ad-ministered 3 × 106 rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat cerebral cortex and rat neurological function was improved significant-ly. These findings suggest that intravenously administered bone marrow mesenchymal stem cells can promote nerve cell regeneration in injured cerebral cortex, which supplement the lost nerve cells.

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

    Science.gov (United States)

    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A

    2014-01-01

    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 fate.

  18. Control of abdominal muscles by brain stem respiratory neurons in the cat

    Science.gov (United States)

    Miller, Alan D.; Ezure, Kazuhisa; Suzuki, Ichiro

    1985-01-01

    The nature of the control of abdominal muscles by the brain stem respiratory neurons was investigated in decerebrate unanesthetized cats. First, it was determined which of the brain stem respiratory neurons project to the lumbar cord (from which the abdominal muscles receive part of their innervation), by stimulating the neurons monopolarly. In a second part of the study, it was determined if lumbar-projecting respiratory neurons make monosynaptic connections with abdominal motoneurons; in these experiments, discriminate spontaneous spikes of antidromically acivated expiratory (E) neurons were used to trigger activity from both L1 and L2 nerves. A large projection was observed from E neurons in the caudal ventral respiratory group to the contralateral upper lumber cord. However, cross-correlation experiments found only two (out of 47 neuron pairs tested) strong monosynaptic connections between brain stem neurons and abdominal motoneurons.

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

    Directory of Open Access Journals (Sweden)

    Alan eMackay-Sim

    2013-03-01

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

  20. 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).

  1. 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.

  2. Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient.

    Directory of Open Access Journals (Sweden)

    Ninette Amariglio

    2009-02-01

    Full Text Available BACKGROUND: Neural stem cells are currently being investigated as potential therapies for neurodegenerative diseases, stroke, and trauma. However, concerns have been raised over the safety of this experimental therapeutic approach, including, for example, whether there is the potential for tumors to develop from transplanted stem cells. METHODS AND FINDINGS: A boy with ataxia telangiectasia (AT was treated with intracerebellar and intrathecal injection of human fetal neural stem cells. Four years after the first treatment he was diagnosed with a multifocal brain tumor. The biopsied tumor was diagnosed as a glioneuronal neoplasm. We compared the tumor cells and the patient's peripheral blood cells by fluorescent in situ hybridization using X and Y chromosome probes, by PCR for the amelogenin gene X- and Y-specific alleles, by MassArray for the ATM patient specific mutation and for several SNPs, by PCR for polymorphic microsatellites, and by human leukocyte antigen (HLA typing. Molecular and cytogenetic studies showed that the tumor was of nonhost origin suggesting it was derived from the transplanted neural stem cells. Microsatellite and HLA analysis demonstrated that the tumor is derived from at least two donors. CONCLUSIONS: This is the first report of a human brain tumor complicating neural stem cell therapy. The findings here suggest that neuronal stem/progenitor cells may be involved in gliomagenesis and provide the first example of a donor-derived brain tumor. Further work is urgently needed to assess the safety of these therapies.

  3. Targeting breast to brain metastatic tumours with death receptor ligand expressing therapeutic stem cells.

    Science.gov (United States)

    Bagci-Onder, Tugba; Du, Wanlu; Figueiredo, Jose-Luiz; Martinez-Quintanilla, Jordi; Shah, Khalid

    2015-06-01

    Characterizing clinically relevant brain metastasis models and assessing the therapeutic efficacy in such models are fundamental for the development of novel therapies for metastatic brain cancers. In this study, we have developed an in vivo imageable breast-to-brain metastasis mouse model. Using real time in vivo imaging and subsequent composite fluorescence imaging, we show a widespread distribution of micro- and macro-metastasis in different stages of metastatic progression. We also show extravasation of tumour cells and the close association of tumour cells with blood vessels in the brain thus mimicking the multi-foci metastases observed in the clinics. Next, we explored the ability of engineered adult stem cells to track metastatic deposits in this model and show that engineered stem cells either implanted or injected via circulation efficiently home to metastatic tumour deposits in the brain. Based on the recent findings that metastatic tumour cells adopt unique mechanisms of evading apoptosis to successfully colonize in the brain, we reasoned that TNF receptor superfamily member 10A/10B apoptosis-inducing ligand (TRAIL) based pro-apoptotic therapies that induce death receptor signalling within the metastatic tumour cells might be a favourable therapeutic approach. We engineered stem cells to express a tumour selective, potent and secretable variant of a TRAIL, S-TRAIL, and show that these cells significantly suppressed metastatic tumour growth and prolonged the survival of mice bearing metastatic breast tumours. Furthermore, the incorporation of pro-drug converting enzyme, herpes simplex virus thymidine kinase, into therapeutic S-TRAIL secreting stem cells allowed their eradication post-tumour treatment. These studies are the first of their kind that provide insight into targeting brain metastasis with stem-cell mediated delivery of pro-apoptotic ligands and have important clinical implications.

  4. How stem cells speak with host immune cells in inflammatory brain diseases.

    Science.gov (United States)

    Pluchino, Stefano; Cossetti, Chiara

    2013-09-01

    Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft-to-host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases.

  5. Gap junction proteins in the blood-brain barrier control nutrient-dependent reactivation of Drosophila neural stem cells.

    Science.gov (United States)

    Spéder, Pauline; Brand, Andrea H

    2014-08-11

    Neural stem cells in the adult brain exist primarily in a quiescent state but are reactivated in response to changing physiological conditions. How do stem cells sense and respond to metabolic changes? In the Drosophila CNS, quiescent neural stem cells are reactivated synchronously in response to a nutritional stimulus. Feeding triggers insulin production by blood-brain barrier glial cells, activating the insulin/insulin-like growth factor pathway in underlying neural stem cells and stimulating their growth and proliferation. Here we show that gap junctions in the blood-brain barrier glia mediate the influence of metabolic changes on stem cell behavior, enabling glia to respond to nutritional signals and reactivate quiescent stem cells. We propose that gap junctions in the blood-brain barrier are required to translate metabolic signals into synchronized calcium pulses and insulin secretion.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kirby, Neil; Chuang, Cynthia; Pouliot, Jean; Hwang, Andrew; Barani, Igor J. [Department of Radiation Oncology, University of California San Francisco, San Francisco, California 94143-1708 (United States)

    2011-10-15

    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.

  7. 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.

  8. 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

  9. Reconstruction of brain circuitry by neural transplants generated from pluripotent stem cells.

    Science.gov (United States)

    Thompson, Lachlan H; Björklund, Anders

    2015-07-01

    Pluripotent stem cells (embryonic stem cells, ESCs, and induced pluripotent stem cells, iPSCs) have the capacity to generate neural progenitors that are intrinsically patterned to undergo differentiation into specific neuronal subtypes and express in vivo properties that match the ones formed during normal embryonic development. Remarkable progress has been made in this field during recent years thanks to the development of more refined protocols for the generation of transplantable neuronal progenitors from pluripotent stem cells, and the access to new tools for tracing of neuronal connectivity and assessment of integration and function of grafted neurons. Recent studies in brains of neonatal mice or rats, as well as in rodent models of brain or spinal cord damage, have shown that ESC- or iPSC-derived neural progenitors can be made to survive and differentiate after transplantation, and that they possess a remarkable capacity to extend axons over long distances and become functionally integrated into host neural circuitry. Here, we summarize these recent developments in the perspective of earlier studies using intracerebral and intraspinal transplants of primary neurons derived from fetal brain, with special focus on the ability of human ESC- and iPSC-derived progenitors to reconstruct damaged neural circuitry in cortex, hippocampus, the nigrostriatal system and the spinal cord, and we discuss the intrinsic and extrinsic factors that determine the growth properties of the grafted neurons and their capacity to establish target-specific long-distance axonal connections in the damaged host brain.

  10. 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)

  11. Paediatric brain-stem gliomas: MRI, FDG-PET and histological grading correlation

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jong Won; Kim, In-One; Cheon, Jung-Eun; Kim, Woo Sun; Moon, Sung Gyu; Kim, Tae Jung; Yeon, Kyung Mo [Seoul National University Hospital, Department of Radiology, Seoul (Korea); Chi, Je Geun [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea); Wang, Kyu-Chang [Seoul National University College of Medicine, Department of Neurosurgery, Seoul (Korea); Chung, June Key [Seoul National University College of Medicine, Department of Nuclear Medicine, Seoul (Korea)

    2006-09-15

    MRI and FDG-PET may predict the histological grading of paediatric brain-stem gliomas. To assess MRI findings and metabolic imaging using FDG-PET of brain-stem gliomas based on histological grading. Included in the study were 20 paediatric patients (age 3-14 years, mean 8.2 years) with brain-stem glioma (five glioblastomas, ten anaplastic astrocytomas and five low-grade astrocytomas). MR images were assessed for the anatomical site of tumour origin, focality, pattern of tumour growth, and enhancement. All glioblastomas were located in the pons and showed diffuse pontine enlargement with focally exophytic features. Eight anaplastic astrocytomas were located in the pons and demonstrated diffuse pontine enlargement without exophytic features. Low-grade astrocytomas were located in the pons, midbrain or medulla and showed focally exophytic growth features and peripheral enhancement. In 12 patients in whom FDG-PET was undertaken, glioblastomas showed hypermetabolic or hypometabolic lesions, anaplastic astrocytomas showed no metabolic change or hypometabolic lesions and low-grade astrocytomas showed hypometabolism compared with the cerebellum. MRI findings correlated well with histological grading of brain-stem gliomas and MRI may therefore predict the histological grading. FDG-PET may be helpful in differentiating between anaplastic astrocytoma and glioblastomas among high-grade tumours. (orig.)

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

    NARCIS (Netherlands)

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

    2013-01-01

    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 wi

  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

    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. Tropism mechanism of stem cells targeting injured brain tissues by stromal cell-derived factor-1

    Institute of Scientific and Technical Information of China (English)

    ZHANG Sai; LIU Xiao-zhi; LIU Zhen-lin; SHANG Chong-zhi; HU Qun-liang

    2009-01-01

    Objective: To explore the role and function of stromal cell-derived factor- 1 (SDF- 1) in stem cells migrating into injured brain area.Methods: Rat-derived nerve stem cells (NSCs) were isolated and cultured routinely. Transwell system was used to observe the migration ability of NSCs into injured nerve cells. Immunocytochemistry was used to explore the expression of chemotactic factor receptor-4 (CXCR-4) in NSCs. In vivo, we applied immunofluorescence technique to observe the migration of NSCs into injured brain area. Immunofluorescence technique and Western blotting were used to test expression level of SDF- 1. After AMD3100 (a special chemical blocker) blocking CXCR-4, the migration ability of NSCs was tested in vivo and in vitro, respectively.Results: NSCs displayed specific tropism for injured nerve cells or traumatic brain area in vivo and in vitro. The expression level of SDF-1 in traumatic brain area increased remarkably and the expression level of CXCR-4 in the NSCs increased simultaneously. After AMD3100 blocking the expression of CXCR-4, the migration ability of NSCs decreased significantly both in vivo and in vitro.Conclusions: SDF-1 may play a key role in stem cells migrating into injured brain area through specially combining with CXCR-4.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-01-01

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

  16. 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.)

  17. Does State Merit-Based Aid Stem Brain Drain?

    Science.gov (United States)

    Zhang, Liang; Ness, Erik C.

    2010-01-01

    In this study, the authors use college enrollment and migration data to test the brain drain hypothesis. Their results suggest that state merit scholarship programs do indeed stanch the migration of "best and brightest" students to other states. In the aggregate and on average, the implementation of state merit aid programs increases the…

  18. Stem Cells Expand Insights into Human Brain Evolution.

    Science.gov (United States)

    Dyer, Michael A

    2016-04-07

    Substantial expansion in the number of cerebral cortex neurons is thought to underlie cognitive differences between humans and other primates, although the mechanisms underlying this expansion are unclear. Otani et al. (2016) utilize PSC-derived brain organoids to study how species-specific differences in cortical progenitor proliferation may underlie cortical evolution.

  19. 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

  20. Classic and novel stem cell niches in brain homeostasis and repair.

    Science.gov (United States)

    Lin, Ruihe; Iacovitti, Lorraine

    2015-12-02

    Neural stem cells (NSCs) critical for the continued production of new neurons and glia are sequestered in distinct areas of the brain called stem cell niches. Until recently, only two forebrain sites, the subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampus, have been recognized adult stem cell niches (Alvarez-Buylla and Lim, 2004; Doetsch et al., 1999a, 1999b; Doetsch, 2003a, 2003b; Lie et al., 2004; Ming and Song, 2005). Nonetheless, the last decade has been witness to a growing literature suggesting that in fact the adult brain contains stem cell niches along the entire extent of the ventricular system. These niches are capable of widespread neurogenesis and gliogenesis, particularly after injury (Barnabé-Heider et al., 2010; Carlén et al., 2009; Decimo et al., 2012; Lin et al., 2015; Lindvall and Kokaia, 2008; Robins et al., 2013) or other inductive stimuli (Bennett et al., 2009; Cunningham et al., 2012; Decimo et al., 2011; Kokoeva et al., 2007, 2005; Lee et al., 2012a, 2012b; Migaud et al., 2010; Pencea et al., 2001b; Sanin et al., 2013; Suh et al., 2007; Sundholm-Peters et al., 2004; Xu et al., 2005; Zhang et al., 2007). This review focuses on the role of these novel and classic brain niches in maintaining adult neurogenesis and gliogenesis in response to normal physiological and injury-related pathological cues. This article is part of a Special Issue entitled SI: Neuroprotection.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1981-03-20

    With the aid of (/sup 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 (/sup 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.

  2. Neural stem cell transplantation with Nogo-66 receptor gene silencing to treat severe traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Dong Wang; Jianjun Zhang; Jingjian Ma; Yuan Mu; Yinghui Zhuang

    2011-01-01

    Inhibition of neurite growth, which is mediated by the Nogo-66 receptor (NgR), affects nerve regeneration following neural stem cell (NSC) transplantation. The present study utilized RNA interference to silence NgR gene expression in NSCs, which were subsequently transplanted into rats with traumatic brain injury. Following transplantation of NSCs transfected with small interfering RNA,typical neural cell-like morphology was detected in injured brain tissues, and was accompanied by absence of brain tissue cavity, increased growth-associated protein 43 mRNA and protein expression,and improved neurological function compared with NSC transplantation alone. Results demonstrated that NSC transplantation with silenced NgR gene promoted functional recovery following brain injury.

  3. Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells.

    Science.gov (United States)

    Lippmann, Ethan S; Azarin, Samira M; Kay, Jennifer E; Nessler, Randy A; Wilson, Hannah K; Al-Ahmad, Abraham; Palecek, Sean P; Shusta, Eric V

    2012-08-01

    The blood-brain barrier (BBB) is crucial to the health of the brain and is often compromised in neurological disease. Moreover, because of its barrier properties, this endothelial interface restricts uptake of neurotherapeutics. Thus, a renewable source of human BBB endothelium could spur brain research and pharmaceutical development. Here we show that endothelial cells derived from human pluripotent stem cells (hPSCs) acquire BBB properties when co-differentiated with neural cells that provide relevant cues, including those involved in Wnt/β-catenin signaling. The resulting endothelial cells have many BBB attributes, including well-organized tight junctions, appropriate expression of nutrient transporters and polarized efflux transporter activity. Notably, they respond to astrocytes, acquiring substantial barrier properties as measured by transendothelial electrical resistance (1,450 ± 140 Ω cm2), and they possess molecular permeability that correlates well with in vivo rodent blood-brain transfer coefficients.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Manohar B Mutnal

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS: MCMV brain infection of newborn mice causes significant loss of NSCs, decreased proliferation of neuronal precursor cells, and marked loss of young neurons.

  6. From pluripotent stem cells to multifunctional cordocytic phenotypes in the human brain: an ultrastructural study.

    Science.gov (United States)

    Pais, Viorel; Danaila, Leon; Pais, Emil

    2012-08-01

    Light microscopy and transmission electron microscopy were used to investigate surgical cases in a variety of pathological conditions (thromboses, tumors, cerebrovascular malformations, Moyamoya disease) to identify and characterize different phenotypes belonging to a new interstitial cell recently described ultrastructurally in the brain and here named "cordocyte." Also, this work is an attempt to identify and characterize precursor/stem cells for cordocytic lineage in the perivascular areas, within perivascular nerves and pia mater (now considered a cordocytic-vascular tissue). Unexpected relationships and functions emerge from observations concerning these phenotypes, almost ubiquitous, but not yet fully studied in the brain.

  7. 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).

  8. Effect of Acupuncture on the Auditory Evoked Brain Stem Potential in Parkinson's Disease

    Institute of Scientific and Technical Information of China (English)

    王玲玲; 何崇; 刘跃光; 朱莉莉

    2002-01-01

    @@ Under the auditory evoked brain stem potential (ABP) examination, the latent period of V wave and the intermittent periods of III-V peak and I-V peak were significantly shortened in Parkinson's disease patients of the treatment group (N=29) after acupuncture treatment. The difference of cumulative scores in Webster's scale was also decreased in correlation analysis. The increase of dopamine in the brain and the excitability of the dopamine neurons may contribute to the therapeutic effects, in TCM terms, of subduing the pathogenic wind and tranquilizing the mind.

  9. Effect of acupuncture on the auditory evoked brain stem potential in Parkinson's disease.

    Science.gov (United States)

    Wang, Lingling; He, Chong; Liu, Yueguang; Zhu, Lili

    2002-03-01

    Under the auditory evoked brain stem potential (ABP) examination, the latent period of V wave and the intermittent periods of III-V peak and I-V peak were significantly shortened in Parkinson's disease patients of the treatment group (N = 29) after acupuncture treatment. The difference of cumulative scores in Webster's scale was also decreased in correlation analysis. The increase of dopamine in the brain and the excitability of the dopamine neurons may contribute to the therapeutic effects, in TCM terms, of subduing the pathogenic wind and tranquilizing the mind.

  10. 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....

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-09-01

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

  12. Microinjection of membrane-impermeable molecules into single neural stem cells in brain tissue.

    Science.gov (United States)

    Wong, Fong Kuan; Haffner, Christiane; Huttner, Wieland B; Taverna, Elena

    2014-05-01

    This microinjection protocol allows the manipulation and tracking of neural stem and progenitor cells in tissue at single-cell resolution. We demonstrate how to apply microinjection to organotypic brain slices obtained from mice and ferrets; however, our technique is not limited to mouse and ferret embryos, but provides a means of introducing a wide variety of membrane-impermeable molecules (e.g., nucleic acids, proteins, hydrophilic compounds) into neural stem and progenitor cells of any developing mammalian brain. Microinjection experiments are conducted by using a phase-contrast microscope equipped with epifluorescence, a transjector and a micromanipulator. The procedure normally takes ∼2 h for an experienced researcher, and the entire protocol, including tissue processing, can be performed within 1 week. Thus, microinjection is a unique and versatile method for changing and tracking the fate of a cell in organotypic slice culture.

  13. Robotics, Stem Cells and Brain Computer Interfaces in Rehabilitation and Recovery from Stroke; Updates and Advances

    Science.gov (United States)

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

    2014-01-01

    Objective To describe the current state and latest advances in robotics, stem cells, and brain computer interfaces in rehabilitation and recovery for stroke. Design The authors of this summary recently reviewed this work as part of a national presentation. The paper represents the information included in each area. Results Each area has seen great advances and challenges as products move to market and experiments are ongoing. Conclusion 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 PMID:25313662

  14. 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).

  15. Characteristics of brain stem auditory evoked potentials in children with hearing impairment due to infectious diseases.

    Science.gov (United States)

    Ječmenica, Jovana Radovan; Opančina, Aleksandra Aleksandar Bajec

    2015-05-01

    Among objective audiologic tests, the most important were tests of brain stem auditory evoked potentials. The objective of the study was to test the configuration, degree of hearing loss, and response characteristics of auditory brain stem evoked potentials in children with hearing loss occurred due to infectious disease. A case control study design was used. The study group consisted of 54 patients referred for a hearing test because of infectious diseases caused by other agents or that occurred as congenital infection. Infectious agents have led to the emergence of various forms of sensorineural hearing loss. We have found deviations from the normal values of absolute and interwave latencies in some children in our group. We found that in the group of children who had the diseases such as purulent meningitis, or were born with rubella virus and cytomegalovirus infection, a retrocochlear damage was present in children with and without cochlear damage.

  16. Evaluation of normal and pathologic appearance in skull base and brain stem with metrizamide CT cisternography

    Energy Technology Data Exchange (ETDEWEB)

    Morimura, Tatsuo; Nakano, Masaru; Maeda, Yukio; Yokota, Masayuki; Kokubu, Kiyokazu; Shimada, Tatsuji (Hyogo College of Medicine (Japan))

    1985-02-01

    Metrizamide CT cisternography was performed in accordance with prone 60/sup 0/ head-down method, to study the normal anatomy of the skull base and brain stem. Cases of empty sellae, Rathke's cleft cyst, mucocele trigeminal neurinoma, pons glioma, acoustic neurinoma and jugular foramen tumor were studied together. As side effects of MCTC there were headache, vomiting and appearance of slow waves on EEG, but no convulsion. Transient encephalopathy was noted when 250 mgI/ml, 12 ml, was used. Using MCTC, it is possible to identify the vertebral artery, posterior inferior cerebellar artery, basillar artery, vessels forming Willis ring as well as II, III, V, VII and VIII cranial nerves. Further, by measuring the brain stem parts on various levels, it may become possible to detect early changes of degenerative disease.

  17. Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation.

    NARCIS (Netherlands)

    Scheper, G.C.; Klok, T. van der; Andel, R.J. van; Berkel, C.G. van; Sissler, M.; Smet, J.; Muravina, T.I.; Serkov, S.V.; Uziel, G.; Bugiani, M.; Schiffmann, R.; Krageloh-Mann, I.; Smeitink, J.A.M.; Florentz, C.; Coster, R. van; Pronk, J.C.; Knaap, M.S. van der

    2007-01-01

    Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) has recently been defined based on a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy. LBSL is an autosomal recessive disease, most often manifesti

  18. Therapeutics with SPION-labeled stem cells for the main diseases related to brain aging: a systematic review

    Science.gov (United States)

    Alvarim, Larissa T; Nucci, Leopoldo P; Mamani, Javier B; Marti, Luciana C; Aguiar, Marina F; Silva, Helio R; Silva, Gisele S; Nucci-da-Silva, Mariana P; DelBel, Elaine A; Gamarra, Lionel F

    2014-01-01

    The increase in clinical trials assessing the efficacy of cell therapy for structural and functional regeneration of the nervous system in diseases related to the aging brain is well known. However, the results are inconclusive as to the best cell type to be used or the best methodology for the homing of these stem cells. This systematic review analyzed published data on SPION (superparamagnetic iron oxide nanoparticle)-labeled stem cells as a therapy for brain diseases, such as ischemic stroke, Parkinson’s disease, amyotrophic lateral sclerosis, and dementia. This review highlights the therapeutic role of stem cells in reversing the aging process and the pathophysiology of brain aging, as well as emphasizing nanotechnology as an important tool to monitor stem cell migration in affected regions of the brain. PMID:25143726

  19. Therapeutics with SPION-labeled stem cells for the main diseases related to brain aging: a systematic review.

    Science.gov (United States)

    Alvarim, Larissa T; Nucci, Leopoldo P; Mamani, Javier B; Marti, Luciana C; Aguiar, Marina F; Silva, Helio R; Silva, Gisele S; Nucci-da-Silva, Mariana P; DelBel, Elaine A; Gamarra, Lionel F

    2014-01-01

    The increase in clinical trials assessing the efficacy of cell therapy for structural and functional regeneration of the nervous system in diseases related to the aging brain is well known. However, the results are inconclusive as to the best cell type to be used or the best methodology for the homing of these stem cells. This systematic review analyzed published data on SPION (superparamagnetic iron oxide nanoparticle)-labeled stem cells as a therapy for brain diseases, such as ischemic stroke, Parkinson's disease, amyotrophic lateral sclerosis, and dementia. This review highlights the therapeutic role of stem cells in reversing the aging process and the pathophysiology of brain aging, as well as emphasizing nanotechnology as an important tool to monitor stem cell migration in affected regions of the brain.

  20. 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...

  1. 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.

  2. Neurons Differentiated from Transplanted Stem Cells Respond Functionally to Acoustic Stimuli in the Awake Monkey Brain.

    Science.gov (United States)

    Wei, Jing-Kuan; Wang, Wen-Chao; Zhai, Rong-Wei; Zhang, Yu-Hua; Yang, Shang-Chuan; Rizak, Joshua; Li, Ling; Xu, Li-Qi; Liu, Li; Pan, Ming-Ke; Hu, Ying-Zhou; Ghanemi, Abdelaziz; Wu, Jing; Yang, Li-Chuan; Li, Hao; Lv, Long-Bao; Li, Jia-Li; Yao, Yong-Gang; Xu, Lin; Feng, Xiao-Li; Yin, Yong; Qin, Dong-Dong; Hu, Xin-Tian; Wang, Zheng-Bo

    2016-07-26

    Here, we examine whether neurons differentiated from transplanted stem cells can integrate into the host neural network and function in awake animals, a goal of transplanted stem cell therapy in the brain. We have developed a technique in which a small "hole" is created in the inferior colliculus (IC) of rhesus monkeys, then stem cells are transplanted in situ to allow for investigation of their integration into the auditory neural network. We found that some transplanted cells differentiated into mature neurons and formed synaptic input/output connections with the host neurons. In addition, c-Fos expression increased significantly in the cells after acoustic stimulation, and multichannel recordings indicated IC specific tuning activities in response to auditory stimulation. These results suggest that the transplanted cells have the potential to functionally integrate into the host neural network.

  3. 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.

  4. Combined Striatum, Brain Stem, and Optic Nerve Involvement due to Mycoplasma pneumoniae in an Ambulatory Child

    Directory of Open Access Journals (Sweden)

    Jin-Won Bae

    2011-05-01

    Full Text Available In children, Mycoplasma pneumoniae encephalitis has been characterized by acute onset of an encephalopathy associated with extrapyramidal symptoms and symmetric basal ganglia with or without brain stem involvement on magnetic resonance imaging. Our case, showing unilateral optic neuritis, ophthalmoplegia, no extrapyramidal symptoms, and typical striatal involvement on magnetic resonance imaging, broadens the spectrum of varying clinical manifestations of childhood M. pneumoniae-associated encephalopathy.

  5. The Regenerative Response of Endogenous Neural Stem/Progenitor Cells to Traumatic Brain Injury

    Science.gov (United States)

    2014-06-09

    neural stem cells in the adjacent SVZ, the largest germinal zone in the mammalian CNS. Ex vivo and in vivo DTI were combined with post-imaging...faults accrued over 50 steps was counted for each hind limb. Controlled Cortical Impact (CCI), which involves craniotomy and impact onto the dura...the subventricular zone (SVZ), a major germinal zone in the adult brain, have potential repair capacity that is not well understood relative to the

  6. [Trismus, trigeminal motor dyssynergy with brain stem lesions (author's transl)].

    Science.gov (United States)

    Jelasic, F; Freitag, V

    1975-08-01

    Paradox activity of masticatory muscles was observed clinically and electromyographically in 4 patients with brain steem lesions who had trismus. There was no activity in the elevators of the jaw on the side affected during voluntary biting, as if the muscles were paralyzed. There was strong activity of the elevators on the side of the trismus on opening the mouth, inactivity on the unaffected side, or inverse activity appeared on both sides. In view of the trigeminal anesthesia on the side of paradox activation, and the absence of pyramidal signs, a stretch reflex mechanism and abolition of inhibition can not be the only basis for these phenomena; so, a disturbance of bilateral synergism, in the sense of an internuclear lesion, is postulated. In one case of motor and sensory paralysis after the extirpation of a meningioma of the cerebellopontine angle, intensive paradox activity was observed, without trismus.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jinqiao, E-mail: jinqiao1977@163.com [Institute of Pediatrics, Children' s Hospital of Fudan University (China); Sha, Bin [Department of Neonatology, Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China); Zhou, Wenhao, E-mail: zhou_wenhao@yahoo.com.cn [Department of Neonatology, Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China); Yang, Yi [Institute of Pediatrics, Children' s Hospital of Fudan University (China)

    2010-03-26

    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.

  8. Brain stem global gene expression profiles in human spina bifida embryos

    Institute of Scientific and Technical Information of China (English)

    Hong Zhao; Xiang Li; Wan-I Lie; Quanren He; Ting Zhang; Xiaoying Zheng; Ran Zhou; Jun Xie

    2011-01-01

    Environmental and genetic factors influence the occurrence of neural tube defects, such as spina bifida.Specific disease expression patterns will help to elucidate the pathogenesis of disease.However, results obtained from animal models, which often exhibit organism specificity, do not fully explain the mechanisms of human spina bifida onset.In the present study, three embryos with a gestational age of approximately 17 weeks and a confirmed diagnosis of spina bifida, as well as 3 age-matched normal embryos, were obtained from abortions.Fetal brain stem tissues were dissected for RNA isolation, and microarray analyses were conducted to examine profiles of gene expression in brain stems of spina bifida and normal embryos using Affymetrix HG-U1 33A 2.0 GeneChip arrays.Of the 14 500 gene transcripts examined, a total of 182 genes exhibited at least 2.5-fold change in expression, including 140 upregulated and 42 downregulated genes.These genes were placed into 19 main functional categories according to the Gene Ontology Consortium database for biological functions.Of the 182 altered genes, approximately 50% were involved in cellular apoptosis, growth, adhesion, cell cycle, stress, DNA replication and repair, signal transduction, nervous system development, oxidoreduction, immune responses, and regulation of gene transcription.Gene expression in multiple biological pathways was altered in the brain stem of human spina bifida embryos.

  9. 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.

  10. 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.

  11. 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.

  12. Strategies for Regenerating Striatal Neurons in the Adult Brain by Using Endogenous Neural Stem Cells

    Directory of Open Access Journals (Sweden)

    Kanako Nakaguchi

    2011-01-01

    Full Text Available Currently, there is no effective treatment for the marked neuronal loss caused by neurodegenerative diseases, such as Huntington's disease (HD or ischemic stroke. However, recent studies have shown that new neurons are continuously generated by endogenous neural stem cells in the subventricular zone (SVZ of the adult mammalian brain, including the human brain. Because some of these new neurons migrate to the injured striatum and differentiate into mature neurons, such new neurons may be able to replace degenerated neurons and improve or repair neurological deficits. To establish a neuroregenerative therapy using this endogenous system, endogenous regulatory mechanisms that can be co-opted for efficient regenerative interventions must be understood, along with any potential drawbacks. Here, we review current knowledge on the generation of new neurons in the adult brain and discuss their potential for use in replacing striatal neurons lost to neurodegenerative diseases, including HD, and to ischemic stroke.

  13. 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.

  14. Brain stem and cerebellum volumetric analysis of Machado Joseph disease patients

    Directory of Open Access Journals (Sweden)

    S T Camargos

    2011-01-01

    Full Text Available Machado-Joseph disease, or spinocerebellar ataxia type 3(MJD/SCA3, is the most frequent late onset spinocerebellar ataxia and results from a CAG repeat expansion in the ataxin-3 gene. Previous studies have found correlation between atrophy of cerebellum and brainstem with age and CAG repeats, although no such correlation has been found with disease duration and clinical manifestations. In this study we test the hypothesis that atrophy of cerebellum and brainstem in MJD/SCA3 is related to clinical severity, disease duration and CAG repeat length as well as to other variables such as age and ICARS (International Cooperative Ataxia Rating Scale. Whole brain high resolution MRI and volumetric measurement with cranial volume normalization were obtained from 15 MJD/SCA3 patients and 15 normal, age and sex-matchedcontrols. We applied ICARS and compared the score with volumes and CAG number, disease duration and age. We found significant correlation of both brain stem and cerebellar atrophy with CAG repeat length, age, disease duration and degree of disability. The Spearman rank correlation was stronger with volumetric reduction of the cerebellum than with brain stem. Our data allow us to conclude that volumetric analysis might reveal progressive degeneration after disease onset, which in turn is linked to both age and number of CAG repeat expansions in SCA 3.

  15. Brain vascular pericytes following ischemia have multipotential stem cell activity to differentiate into neural and vascular lineage cells.

    Science.gov (United States)

    Nakagomi, Takayuki; Kubo, Shuji; Nakano-Doi, Akiko; Sakuma, Rika; Lu, Shan; Narita, Aya; Kawahara, Maiko; Taguchi, Akihiko; Matsuyama, Tomohiro

    2015-06-01

    Brain vascular pericytes (PCs) are a key component of the blood-brain barrier (BBB)/neurovascular unit, along with neural and endothelial cells. Besides their crucial role in maintaining the BBB, increasing evidence shows that PCs have multipotential stem cell activity. However, their multipotency has not been considered in the pathological brain, such as after an ischemic stroke. Here, we examined whether brain vascular PCs following ischemia (iPCs) have multipotential stem cell activity and differentiate into neural and vascular lineage cells to reconstruct the BBB/neurovascular unit. Using PCs extracted from ischemic regions (iPCs) from mouse brains and human brain PCs cultured under oxygen/glucose deprivation, we show that PCs developed stemness presumably through reprogramming. The iPCs revealed a complex phenotype of angioblasts, in addition to their original mesenchymal properties, and multidifferentiated into cells from both a neural and vascular lineage. These data indicate that under ischemic/hypoxic conditions, PCs can acquire multipotential stem cell activity and can differentiate into major components of the BBB/neurovascular unit. Thus, these findings support the novel concept that iPCs can contribute to both neurogenesis and vasculogenesis at the site of brain injuries.

  16. Stemming the impact of health professional brain drain from Africa: a systemic review of policy options

    Directory of Open Access Journals (Sweden)

    Edward Zimbudzi

    2013-06-01

    Full Text Available Africa has been losing professionally trained health workers who are the core of the health system of this continent for many years. Faced with an increased burden of disease and coupled by a massive exodus of the health workforce, the health systems of many African nations are risking complete paralysis. Several studies have suggested policy options to reduce brain drain from Africa. The purpose of this paper is to review possible policies, which can stem the impact of health professional brain drain from Africa. A systemic literature review was conducted. Cinahl, Science Direct and PubMed databases were searched with the following terms: health professional brain drain from Africa and policies for reducing impact of brain drain from Africa. References were also browsed for relevant articles. A total of 425 articles were available for the study but only 23 articles met the inclusion criteria. The review identified nine policy options, which were being implemented in Africa, but the most common was task shifting which had success in several African countries. This review has demonstrated that there is considerable consensus on task shifting as the most appropriate and sustainable policy option for reducing the impact of health professional brain drain from Africa.

  17. Activation of endogenous neural stem cells in experimental intracerebral hemorrhagic rat brains

    Institute of Scientific and Technical Information of China (English)

    唐涛; 黎杏群; 武衡; 罗杰坤; 张花先; 罗团连

    2004-01-01

    Background Many researchers suggest that adult mammalian central nervous system (CNS) is incapable of completing self-repair or regeneration. And there are accumulating lines of evidence which suggest that endogenous neural stem cells (NSCs) are activated in many pathological conditions, including stroke in the past decades, which might partly account for rehabilitation afterwards. In this study, we investigated whether there was endogenous neural stem cell activation in intracerebral hemorrhagic (ICH) rat brains.Methods After ICH induction by stereotactical injection of collagenase type Ⅶ into globus pallidus, 5-Bromo-2 Deoxyuridine (BrdU) was administered intraperitoneally to label newborn cells. Immunohistochemical method was used to detect Nestin, a marker for neural stem cells, and BrdU.Results Nestin-positive or BrdU-Labeled cells were predominantly located at 2 sites: basal ganglion around hemotoma, ependyma and nearby subventricular zone (SVZ). No positive cells for the 2 markers were found in the 2 sites of normal control group and sham group, as well as in non-leisoned parenchyma, both hippocampi and olfactory bulbs in the 4 groups. Nestin+ cells presented 4 types of morphology, and BrdU+ nucleus were polymorphologic. Postive cell counting around hemotoma showed that at day 2, Nestin+ cells were seen around hemotoma in model group , the number of which increased at day 4, day 7(P<0.01), peaked at day 14(P<0.05), and reduced significantly by day 28(P<0.01).Conclusion Endogenous neural stem cells were activated in experimental intracerebral hemorrhagic rat brains.

  18. Comparitive Study Between Cnventional and Hyperfractionaltion Radiation Therapy for The Treatment of Brain Stem Tumors

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    Laila Fares * (MD, Mamdouh Salama** (MD Manal Moawad

    2001-06-01

    Full Text Available Brain stem tumors are special challenge because primarily of their location and the neurologic effect caused by these groups of tumors (Paul 1997. Radiation therapy improves survival for brain stem tumors and stabilizes or reverses neurologic dysfunction in 75-90% of patients. The main domain of applicability of hyperfractionation would be in tumor sites where the dose limiting tissue is late reacting and whose effective control requires the delivery of doses beyond tolerance (Awwad, 1990, hence the rationale for the use of hyperfractionation in brain stem lesions. The purpose of this work is to find out the best radiation protocol in this group of patients comparing conventional fractionation and hyperafractionation. This study included 46 patients which brainstem tumors treated in Radiation Oncology and Neurosurgery Departments Ain Shams University between February 1998 and May 2000. These patients had been randomly distributed in 2 groups A and B. The first group treated by conventional radiotherapy protocol and the second group treated by hyperfractionation radiation protocol. By the end of the study, the median over all survival and median time for disease progression were calculated for each group. Age, neurologic status at presentation and anatomical location were significant prognostic factors. By the end of this study clicinal evalualion had no significant difference between both groups but the median over all survival for the two groups was 10.5 months, the median survival for group A was 9.4 months and that for group B was 11.5 months which was statistically significant P < 0.02. On the other hand the percentage of patient with one year survival for group A & B (22%, 32% respectively. The rate of acute (early reaction of radiation is slightly higher in hyperfracticmaticm than conventional fractionation but the late reactions occur with same frequency with both regimens.

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

    Science.gov (United States)

    Jubault, Thomas; Brambati, Simona M; Degroot, Clotilde; Kullmann, Benoît; Strafella, Antonio P; Lafontaine, Anne-Louise; Chouinard, Sylvain; Monchi, Oury

    2009-12-10

    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.

  20. 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.

  1. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment

    Institute of Scientific and Technical Information of China (English)

    Xianchao Li; Wensheng Hou; Xiaoying Wu; Wei Jiang; Haiyan Chen; Nong Xiao; Ping Zhou

    2014-01-01

    Bone marrow mesenchymal stem cell transplantation is an effective treatment for neonatal hy-poxic-ischemic brain damage. However, the in vivo transplantation effects are poor and their survival, colonization and differentiation efifciencies are relatively low. Red or near-infrared light from 600-1,000 nm promotes cellular migration and prevents apoptosis. Thus, we hypothesized that the combination of red light with bone marrow mesenchymal stem cell transplantation would be effective for the treatment of hypoxic-ischemic brain damage. In this study, the migra-tion and colonization of cultured bone marrow mesenchymal stem cells on primary neurons after oxygen-glucose deprivation were detected using Transwell assay. The results showed that, after a 40-hour irradiation under red light-emitting diodes at 660 nm and 60 mW/cm2, an increasing number of green lfuorescence-labeled bone marrow mesenchymal stem cells migrated towards hypoxic-ischemic damaged primary neurons. Meanwhile, neonatal rats with hypoxic-ischemic brain damage were given an intraperitoneal injection of 1 × 106 bone marrow mesenchymal stem cells, followed by irradiation under red light-emitting diodes at 660 nm and 60 mW/cm2 for 7 successive days. Shuttle box test results showed that, after phototherapy and bone marrow mesenchymal stem cell transplantation, the active avoidance response rate of hypoxic-ischemic brain damage rats was significantly increased, which was higher than that after bone marrow mesenchymal stem cell transplantation alone. Experimental ifndings indicate that 660 nm red light emitting diode irradiation promotes the migration of bone marrow mesenchymal stem cells, thereby enhancing the contribution of cell transplantation in the treatment of hypox-ic-ischemic brain damage.

  2. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment.

    Science.gov (United States)

    Li, Xianchao; Hou, Wensheng; Wu, Xiaoying; Jiang, Wei; Chen, Haiyan; Xiao, Nong; Zhou, Ping

    2014-02-01

    Bone marrow mesenchymal stem cell transplantation is an effective treatment for neonatal hypoxic-ischemic brain damage. However, the in vivo transplantation effects are poor and their survival, colonization and differentiation efficiencies are relatively low. Red or near-infrared light from 600-1,000 nm promotes cellular migration and prevents apoptosis. Thus, we hypothesized that the combination of red light with bone marrow mesenchymal stem cell transplantation would be effective for the treatment of hypoxic-ischemic brain damage. In this study, the migration and colonization of cultured bone marrow mesenchymal stem cells on primary neurons after oxygen-glucose deprivation were detected using Transwell assay. The results showed that, after a 40-hour irradiation under red light-emitting diodes at 660 nm and 60 mW/cm(2), an increasing number of green fluorescence-labeled bone marrow mesenchymal stem cells migrated towards hypoxic-ischemic damaged primary neurons. Meanwhile, neonatal rats with hypoxic-ischemic brain damage were given an intraperitoneal injection of 1 × 10(6) bone marrow mesenchymal stem cells, followed by irradiation under red light-emitting diodes at 660 nm and 60 mW/cm(2) for 7 successive days. Shuttle box test results showed that, after phototherapy and bone marrow mesenchymal stem cell transplantation, the active avoidance response rate of hypoxic-ischemic brain damage rats was significantly increased, which was higher than that after bone marrow mesenchymal stem cell transplantation alone. Experimental findings indicate that 660 nm red light emitting diode irradiation promotes the migration of bone marrow mesenchymal stem cells, thereby enhancing the contribution of cell transplantation in the treatment of hypoxic-ischemic brain damage.

  3. Science Letters: Brain natriuretic peptide: A potential indicator of cardiomyogenesis after autologous mesenchymal stem cell transplantation?

    Institute of Scientific and Technical Information of China (English)

    LI Nan; WANG Jian-an

    2006-01-01

    We observed in a pilot study that there was a transient elevation of brain natriuretic peptide (BNP) level shortly after the transplantation in the patient with ischemic heart failure, which is unexplainable by the simultaneous increase of the cardiac output and six-minute walk distance. Similar findings were observed in the phase I trial. We postulated on the basis of the finding of Fukuda in vitro that this transient elevation of BNP level against the improvement of cardiac function and exercise capacity might indicate cardiomyogenesis in patients after mesenchymal stem cell transplantation. Further study is warranted to verify the hypothesis.

  4. 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.

  5. Stem cell-based delivery of brain-derived neurotrophic factor gene in the rat retina.

    Science.gov (United States)

    Park, Hae-Young Lopilly; Kim, Jie Hyun; Sun Kim, Hwa; Park, Chan Kee

    2012-08-21

    As an alternative to a viral vector, the application of stem cells to transfer specific genes is under investigation in various organs. Using this strategy may provide more effective method to supply neurotrophic factor to the neurodegenerative diseases caused by neurotrophic factor deprivation. This study investigated the possibility and efficacy of stem cell-based delivery of the brain-derived neurotrophic factor (BDNF) gene to rat retina. Rat BDNF cDNA was transduced into rat bone marrow mesenchymal stem cells (rMSCs) using a retroviral vector. Its incorporation into the experimental rat retina and the expression of BDNF after intravitreal injection or subretinal injection were detected by real-time PCR, western blot analysis, and immunohistochemical staining. For the incorporated rMSCs, retinal-specific marker staining was performed to investigate the changes in morphology and the characteristics of the stem cells. Transduction of the rMSCs by retrovirus was effective, and the transduced rMSCs expressed high levels of the BDNF gene and protein. The subretinal injection of rMSCs produced rMSC migration and incorporation into the rat retina (about 15.7% incorporation rate), and retinal BDNF mRNA and protein expression was increased at 4 weeks after transplantation. When subretinal injection of rMSCs was applied to axotomized rat retina, it significantly increased the expression of BDNF until 4 weeks after transplantation. Some of the transplanted rMSCs exhibited morphological changes, but the retinal-specific marker stain was not sufficient to indicate whether neuronal differentiation had occurred. Using mesenchymal stem cells to deliver the BDNF gene to the retina may provide new treatment for glaucoma.

  6. Research progress in brain tumor stem cells%脑肿瘤干细胞的研究现状

    Institute of Scientific and Technical Information of China (English)

    王欣欣; 刘季平

    2012-01-01

    BACKGROUND: Research in recent years has discovered some stem cell-like cells exist in brain tumors, which have theproperties of endless cell proliferation, uncontrolled self-renewal and multi-directional differentiation, and they are called as braintumor stem cells. Brain tumor stem cells play a key role in the progress of tumorigenesis, growth, invasion, metastasis andrecurrence.OBJECTIVE: To conclude and explore the current studies on brain tumor stem cells.METHODS: A computer-based search of Pubmed Database was performed to retrieve relevant articles about brain tumor andbrain tumor stem cells published from January 1977 to July 2011. Books on stem cells and brain tumor stem cells were alsoretrieved. The data were selected primarily, and 32 articles related to brain tumor stem cells were selected.RESULTS AND CONCLUSION: Brain tumor stem cells exist in malignant brain tumor, and they are the origin of the occurrence,development, metastasis and recurrence of malignant brain tumor. Brain tumor stem cells express CD133, Nestin protein andABC transporter in malignant brain tumors. Recently, a simple method has been obtained to isolate brain tumor stem cells. Theproportion of CD133 positive tumor stem cells is positively correlated with the severity of malignant brain tumors, which can beused as a diagnostic indicator of prognosis.%背景:在脑肿瘤中存在一种具有自我更新、无限增殖与多向分化能力的细胞,即脑肿瘤干细胞.脑肿瘤干细胞被认为是脑肿瘤发生、发展、转移与复发的根源.目的:总结和探讨脑肿瘤干细胞的研究现状.方法:以"脑肿瘤、脑肿瘤干细胞"为检索词,应该计算机检索Pubmed 数据库1977-01/2011-07的相关文章,并查阅与干细胞及脑肿瘤干细胞实验有关的书籍,对资料进行初审,选取符合要求的有关文章共32 篇.结果与结论:在恶性脑肿瘤中存在脑肿瘤干细胞.脑肿瘤干细胞是恶性脑肿瘤发生、发展、转移及复发的

  7. Activin and TGF-β effects on brain development and neural stem cells.

    Science.gov (United States)

    Rodríguez-Martínez, Griselda; Velasco, Iván

    2012-11-01

    Transforming Growth Factor-β (TGF-β) family members are ubiquitously expressed, participating in the regulation of many processes in different cell types both in embryonic and adult stages. Several members of this family, including Activins, TGF-β1-3 and Nodal, have been implicated in the development and maintenance of various organs, in which stem cells play important roles. Although TGF-β was initially considered an injury-related cytokine, it became clear that not only TGF-β, but other members of this family, play critical roles in morphogenesis and cell lineage specification. During brain development, Activin and TGF-βs as well as their cognate receptors, are expressed in different patterns. The roles of Activin and TGF-β during CNS development are sometimes contradictory, because these proteins present different actions depending on the cell type and the context. The aim of this review is to summarize current information on the actions of TGF-β members during developing brain, and also on Neural Stem/Progenitor Cells (NSPC). We focus on the TGF-β subgroup, specifically on the effects of TGF-β1 and Activin A. In the first section we describe the main characteristics of the ligands, its receptors as well as the proteins and mechanisms involved in signaling. Next, we discuss the main advances concerning TGF-β1 and Activin actions during brain development and their roles in NSPC fate decision and neuroprotection both in vitro and in vivo. The emerging picture from these studies suggests that these growth factors can be used to manipulate neurogenesis and might help to achieve restoration after brain deterioration.

  8. Brain components

    Science.gov (United States)

    ... can make complex movements without thinking. The brain stem connects the brain with the spinal cord and is composed of ... structures: the midbrain, pons, and medulla oblongata. The brain stem provides us with automatic functions that are necessary ...

  9. Utilizing pharmacotherapy and mesenchymal stem cell therapy to reduce inlfammation following traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Sherwin Mashkouri; Marci G. Crowley; Michael G. Liska; Sydney Corey; Cesar V. Borlongan

    2016-01-01

    The pathologic process of chronic phase traumatic brain injury is associated with spreading inlfamma-tion, cell death, and neural dysfunction. It is thought that sequestration of inlfammatory mediators can facilitate recovery and promote an environment that fosters cellular regeneration. Studies have targeted post-traumatic brain injury inlfammation with the use of pharmacotherapy and cell therapy. These thera-peutic options are aimed at reducing the edematous and neurodegenerative inlfammation that have been associated with compromising the integrity of the blood-brain barrier. Although studies have yielded posi-tive results from anti-inlfammatory pharmacotherapy and cell therapy individually, emerging research has begun to target inlfammation using combination therapy. The joint use of anti-inlfammatory drugs along-side stem cell transplantation may provide better clinical outcomes for traumatic brain injury patients. Despite the promising results in this ifeld of research, it is important to note that most of the studies men-tioned in this review have completed their studies using animal models. Translation of this research into a clinical setting will require additional laboratory experiments and larger preclinical trials.

  10. Neural stem cell-based dual suicide gene delivery for metastatic brain tumors.

    Science.gov (United States)

    Wang, C; Natsume, A; Lee, H J; Motomura, K; Nishimira, Y; Ohno, M; Ito, M; Kinjo, S; Momota, H; Iwami, K; Ohka, F; Wakabayashi, T; Kim, S U

    2012-11-01

    In our previous works, we demonstrated that human neural stem cells (NSCs) transduced with the cytosine deaminase (CD) gene showed remarkable 'bystander killer effect' on glioma and medulloblastoma cells after administration of the prodrug 5-fluorocytosine (5-FC). In addition, herpes simplex virus thymidine kinase (TK) is a widely studied enzyme used for suicide gene strategies, for which the prodrug is ganciclovir (GCV). To apply this strategy to brain metastasis treatment, we established here a human NSC line (F3.CD-TK) expressing the dual suicide genes CD and TK. We examined whether F3.CD-TK cells intensified the antitumor effect on lung cancer brain metastases. In vitro studies showed that F3.CD-TK cells exerted a marked bystander effect on human lung cancer cells after treatment with 5-FC and GCV. In a novel experimental brain metastases model, intravenously administered F3 cells migrated near lung cancer metastatic lesions, which were induced by the injection of lung cancer cells via the intracarotid artery. More importantly, F3.CD-TK cells in the presence of prodrugs 5-FC and GCV decreased tumor size and considerably prolonged animal survival. The results of the present study indicate that the dual suicide gene-engineered, NSC-based treatment strategy might offer a new promising therapeutic modality for brain metastases.

  11. Injection of SDF-1 loaded nanoparticles following traumatic brain injury stimulates neural stem cell recruitment.

    Science.gov (United States)

    Zamproni, Laura N; Mundim, Mayara V; Porcionatto, Marimelia A; des Rieux, Anne

    2017-03-15

    Recruiting neural stem cell (NSC) at the lesion site is essential for central nervous system repair. This process could be triggered by the local delivery of the chemokine SDF-1. We compared two PLGA formulations for local brain SDF-1 delivery: SDF-1 loaded microspheres (MS) and SDF-1 loaded nanoparticles (NP). Both formulations were able to encapsulate more than 80% of SDF-1 but presented different release profiles, with 100% of SDF-1 released after 6days for the MS and with 25% of SDF-1 released after 2 weeks for NP. SDF-1 bioactivity was demonstrated by a chemotactic assay. When injected in mouse brain after traumatic brain injury, only SDF-1 nanoparticles induced NSC migration to the damage area. More neuroblasts (DCX+ cells) could be visualized around the lesions treated with NP SDF-1 compared to the other conditions. Rostral migratory stream destabilization with massive migration of DCX+ cell toward the perilesional area was observed 2 weeks after NP SDF-1 injection. Local injection of SDF-1-loaded nanoparticles induces recruitment of NSC and could be promising for brain injury lesion.

  12. 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.

  13. Maternal inflammation contributes to brain overgrowth and autism-associated behaviors through altered redox signaling in stem and progenitor cells.

    Science.gov (United States)

    Le Belle, Janel E; Sperry, Jantzen; Ngo, Amy; Ghochani, Yasmin; Laks, Dan R; López-Aranda, Manuel; Silva, Alcino J; Kornblum, Harley I

    2014-11-11

    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.

  14. In vivo imaging of endogenous neural stem cells in theadult brain

    Institute of Scientific and Technical Information of China (English)

    Maria Adele Rueger; Michael Schroeter

    2015-01-01

    The discovery of endogenous neural stem cells (eNSCs) inthe adult mammalian brain with their ability to self-renewand differentiate into functional neurons, astrocytes andoligodendrocytes has raised the hope for novel therapiesof neurological diseases. Experimentally, those eNSCscan be mobilized in vivo , enhancing regeneration andaccelerating functional recovery after, e.g., focal cerebralischemia, thus constituting a most promising approachin stem cell research. In order to translate those currentexperimental approaches into a clinical setting in thefuture, non-invasive imaging methods are required tomonitor eNSC activation in a longitudinal and intraindividualmanner. As yet, imaging protocols to assesseNSC mobilization non-invasively in the live brain remainscarce, but considerable progress has been made inthis field in recent years. This review summarizes anddiscusses the current imaging modalities suitable tomonitor eNSCs in individual experimental animals overtime, including optical imaging, magnetic resonancetomography and-spectroscopy, as well as positronemission tomography (PET). Special emphasis is puton the potential of each imaging method for a possibleclinical translation, and on the specificity of the signalobtained. PET-imaging with the radiotracer 3'-deoxy-3'-[18F]fluoro-L-thymidine in particular constitutes amodality with excellent potential for clinical translationbut low specificity; however, concomitant imaging ofneuroinflammation is feasible and increases its specificity.The non-invasive imaging strategies presented here allowfor the exploitation of novel treatment strategies basedupon the regenerative potential of eNSCs, and will helpto facilitate a translation into the clinical setting.

  15. Development and modulation of intrinsic membrane properties control the temporal precision of auditory brain stem neurons.

    Science.gov (United States)

    Franzen, Delwen L; Gleiss, Sarah A; Berger, Christina; Kümpfbeck, Franziska S; Ammer, Julian J; Felmy, Felix

    2015-01-15

    Passive and active membrane properties determine the voltage responses of neurons. Within the auditory brain stem, refinements in these intrinsic properties during late postnatal development usually generate short integration times and precise action-potential generation. This developmentally acquired temporal precision is crucial for auditory signal processing. How the interactions of these intrinsic properties develop in concert to enable auditory neurons to transfer information with high temporal precision has not yet been elucidated in detail. Here, we show how the developmental interaction of intrinsic membrane parameters generates high firing precision. We performed in vitro recordings from neurons of postnatal days 9-28 in the ventral nucleus of the lateral lemniscus of Mongolian gerbils, an auditory brain stem structure that converts excitatory to inhibitory information with high temporal precision. During this developmental period, the input resistance and capacitance decrease, and action potentials acquire faster kinetics and enhanced precision. Depending on the stimulation time course, the input resistance and capacitance contribute differentially to action-potential thresholds. The decrease in input resistance, however, is sufficient to explain the enhanced action-potential precision. Alterations in passive membrane properties also interact with a developmental change in potassium currents to generate the emergence of the mature firing pattern, characteristic of coincidence-detector neurons. Cholinergic receptor-mediated depolarizations further modulate this intrinsic excitability profile by eliciting changes in the threshold and firing pattern, irrespective of the developmental stage. Thus our findings reveal how intrinsic membrane properties interact developmentally to promote temporally precise information processing.

  16. Acoustic emissions from the inner ear and brain stem responses in type 2 diabetics

    Directory of Open Access Journals (Sweden)

    Jabbari Moghaddam Y

    2011-12-01

    Full Text Available Yalda Jabbari MoghaddamDepartment of Otolaryngology, Head and Neck Surgery, Tabriz University of Medical Sciences, Tabriz, IranBackground: The purpose of this study was to evaluate the auditory brain stem response (ABR and acoustic emissions of the inner ear (OAE in middle-aged type 2 diabetics.Methods: Fifty type 2 diabetic and nondiabetic patients aged 40–50 years and attending the Tabriz Medical University outpatient clinics were recruited for this study during 2009–2010. All ABR and OAE procedures were implemented by an audiometrist. The relationship between ABR and OAE findings and demographic, laboratory, and clinical characteristics was investigated.Results: Fifty patients (34 female and 16 male of average age 45.7 ± 3.0 years were entered into the study. In the type 2 diabetic group, disordered ABR was found in at least one ear in 8% of cases and disordered OAE was recorded in at least one ear in 16% of cases, with no significant difference between the diabetic and nondiabetic groups. Mean age, duration of diabetes, serum HbA1c levels, and prevalence of female gender were higher in the diabetic group.Conclusion: According to our findings, the prevalence of ABR and OAE is not significantly different between type 2 diabetics and nondiabetics.Keywords: sensorineural hearing loss, diabetes, auditory brain stem response, otoacoustic emission

  17. 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.

  18. 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

    2003-01-01

    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

  19. MicroRNA network changes in the brain stem underlie the development of hypertension.

    Science.gov (United States)

    DeCicco, Danielle; Zhu, Haisun; Brureau, Anthony; Schwaber, James S; Vadigepalli, Rajanikanth

    2015-09-01

    Hypertension is a major chronic disease whose molecular mechanisms remain poorly understood. We compared neuroanatomical patterns of microRNAs in the brain stem of the spontaneous hypertensive rat (SHR) to the Wistar Kyoto rat (WKY, control). We quantified 419 well-annotated microRNAs in the nucleus of the solitary tract (NTS) and rostral ventrolateral medulla (RVLM), from SHR and WKY rats, during three main stages of hypertension development. Changes in microRNA expression were stage- and region-dependent, with a majority of SHR vs. WKY differential expression occurring at the hypertension onset stage in NTS versus at the prehypertension stage in RVLM. Our analysis identified 24 microRNAs showing time-dependent differential expression in SHR compared with WKY in at least one brain region. We predicted potential gene regulatory targets corresponding to catecholaminergic processes, neuroinflammation, and neuromodulation using the miRWALK and RNA22 databases, and we tested those bioinformatics predictions using high-throughput quantitative PCR to evaluate correlations of differential expression between the microRNAs and their predicted gene targets. We found a novel regulatory network motif consisting of microRNAs likely downregulating a negative regulator of prohypertensive processes such as angiotensin II signaling and leukotriene-based inflammation. Our results provide new evidence on the dynamics of microRNA expression in the development of hypertension and predictions of microRNA-mediated regulatory networks playing a region-dependent role in potentially altering brain-stem cardiovascular control circuit function leading to the development of hypertension.

  20. Physical weight loading induces expression of tryptophan hydroxylase 2 in the brain stem.

    Directory of Open Access Journals (Sweden)

    Joon W Shim

    Full Text Available Sustaining brain serotonin is essential in mental health. Physical activities can attenuate mental problems by enhancing serotonin signaling. However, such activity is not always possible in disabled individuals or patients with dementia. Knee loading, a form of physical activity, has been found to mimic effects of voluntary exercise. Focusing on serotonergic signaling, we addressed a question: Does local mechanical loading to the skeleton elevate expression of tryptophan hydroxylase 2 (tph2 that is a rate-limiting enzyme for brain serotonin? A 5 min knee loading was applied to mice using 1 N force at 5 Hz for 1,500 cycles. A 5-min treadmill running was used as an exercise (positive control, and a 90-min tail suspension was used as a stress (negative control. Expression of tph2 was determined 30 min - 2 h in three brain regions --frontal cortex (FC, ventromedial hypothalamus (VMH, and brain stem (BS. We demonstrated for the first time that knee loading and treadmill exercise upregulated the mRNA level of tph2 in the BS, while tail suspension downregulated it. The protein level of tph2 in the BS was also upregulated by knee loading and downregulated by tail suspension. Furthermore, the downregulation of tph2 mRNA by tail suspension can be partially suppressed by pre-application of knee loading. The expression of tph2 in the FC and VMH was not significantly altered with knee loading. In this study we provided evidence that peripheral mechanical loading can activate central tph2 expression, suggesting that physical cues may mediate tph2-cathalyzed serotonergic signaling in the brain.

  1. The role of cancer stem cells and miRNAs in defining the complexities of brain metastasis

    OpenAIRE

    2013-01-01

    Researchers and clinicians have been challenged with the development of therapies for the treatment of cancer patients whose tumors metastasized to the brain. Among the most lethal weapons known today, current management of brain metastases involves multiple therapeutic modalities that provide little, if any, for improving the quality of life and overall survival. Recently the role of cancer stem cells (CSCs) in the development of cancer has been studied extensively, and thus its role in the ...

  2. 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

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

    Institute of Scientific and Technical Information of China (English)

    Zhong-jun Zhang; Ya-jun Li; Xiao-guang Liu; Feng-xiao Huang; Tie-jun Liu; Dong-mei Jiang; Xue-man Lv; Min Luo

    2015-01-01

    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 × 106 human umbilical cord blood stem cells. After 30 days, the maximum load, max-imum 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 neu-rotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These ifndings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, im-prove biomechanical properties, and contribute to the recovery after injury.

  4. Collateralization of the pathways descending from the cerebral cortex to brain stem and spinal cord in cat and monkey

    NARCIS (Netherlands)

    K. Keizer (Koos)

    1989-01-01

    textabstractThe present study deals with the collateralization of the descending pathways from the cerebral cortex to the brain stem and the spinal cord in cat and monkey. The distributions of the branching cortical neurons were studied using retrograde fluorescent tracers. In addition, a new retrog

  5. Cognitive improvement following transvenous adipose-derived mesenchymal stem cell transplantation in a rat model of traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Dongfei Li; Chun Yang; Rongmei Qu; Huiying Yang; Meichun Yu; Hui Tao; Jingxing Dai; Lin Yuan

    2011-01-01

    The effects of adipose-derived mesenchymal stem cell (ADMSC) transplantation for the repair of traumatic brain injury remain poorly understood. The present study observed neurological functional changes in a rat model of traumatic brain injury following ADMSC transplantation via the tail vein.Cell transplants were observed in injured cerebral cortex, and expression of brain-derived nerve growth factor was significantly increased in the injured hippocampus following transplantation. Results demonstrated that transvenous ADMSC transplants migrated to the injured cerebral cortex and significantly improved cognitive function.

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

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    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

  7. Modeling learning in brain stem and cerebellar sites responsible for VOR plasticity

    Science.gov (United States)

    Quinn, K. J.; Didier, A. J.; Baker, J. F.; Peterson, B. W.

    1998-01-01

    A simple model of vestibuloocular reflex (VOR) function was used to analyze several hypotheses currently held concerning the characteristics of VOR plasticity. The network included a direct vestibular pathway and an indirect path via the cerebellum. An optimization analysis of this model suggests that regulation of brain stem sites is critical for the proper modification of VOR gain. A more physiologically plausible learning rule was also applied to this network. Analysis of these simulation results suggests that the preferred error correction signal controlling gain modification of the VOR is the direct output of the accessory optic system (AOS) to the vestibular nuclei vs. a signal relayed through the cerebellum via floccular Purkinje cells. The potential anatomical and physiological basis for this conclusion is discussed, in relation to our current understanding of the latency of the adapted VOR response.

  8. Control of Outer Radial Glial Stem Cell Mitosis in the Human Brain

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    Bridget E.L. Ostrem

    2014-08-01

    Full Text Available Evolutionary expansion of the human neocortex is partially attributed to a relative abundance of neural stem cells in the fetal brain called outer radial glia (oRG. oRG cells display a characteristic division mode, mitotic somal translocation (MST, in which the soma rapidly translocates toward the cortical plate immediately prior to cytokinesis. MST may be essential for progenitor zone expansion, but the mechanism of MST is unknown, hindering exploration of its function in development and disease. Here, we show that MST requires activation of the Rho effector ROCK and nonmuscle myosin II, but not intact microtubules, centrosomal translocation into the leading process, or calcium influx. MST is independent of mitosis and distinct from interkinetic nuclear migration and saltatory migration. Our findings suggest that disrupted MST may underlie neurodevelopmental diseases affecting the Rho-ROCK-myosin pathway and provide a foundation for future exploration of the role of MST in neocortical development, evolution, and disease.

  9. [Diagnostic significance of the spinal-brain stem polysynaptic reflex and the period of inhibition].

    Science.gov (United States)

    Ivanichev, G A

    1985-01-01

    Electrical stimulation of the radial nerve associated with voluntary contraction of the shoulder girdle inhibited bioelectrical activity not only in the muscles of the hypothenar but also in the proximal muscles. In resting muscles, such stimulation elicited a reflex response with a large latent period. With weak voluntary tension stimulation elicited a reflex response while in the presence of considerable contraction the reflex response merged with bioelectrical activity, with a clearly demonstrable subsequent period of inhibition. The current viewpoint about the antidromal blockade of the segmental motoneurons is debated. It is suggested that the polysynaptic reflex and the inhibition period are connected with the same level of realization -- the oral portions of the brain stem.

  10. Bioenergetics failure and oxidative stress in brain stem mediates cardiovascular collapse associated with fatal methamphetamine intoxication.

    Directory of Open Access Journals (Sweden)

    Faith C H Li

    Full Text Available BACKGROUND: Whereas sudden death, most often associated with cardiovascular collapse, occurs in abusers of the psychostimulant methamphetamine (METH, the underlying mechanism is much less understood. The demonstration that successful resuscitation of an arrested heart depends on maintained functionality of the rostral ventrolateral medulla (RVLM, which is responsible for the maintenance of stable blood pressure, suggests that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse. We tested the hypothesis that cessation of brain stem cardiovascular regulation because of a loss of functionality in RVLM mediated by bioenergetics failure and oxidative stress underlies the cardiovascular collapse elicited by lethal doses of METH. METHODOLOGY/PRINCIPAL FINDINGS: Survival rate, cardiovascular responses and biochemical or morphological changes in RVLM induced by intravenous administration of METH in Sprague-Dawley rats were investigated. High doses of METH induced significant mortality within 20 min that paralleled concomitant the collapse of arterial pressure or heart rate and loss of functionality in RVLM. There were concurrent increases in the concentration of METH in serum and ventrolateral medulla, along with tissue anoxia, cessation of microvascular perfusion and necrotic cell death in RVLM. Furthermore, mitochondrial respiratory chain enzyme activity or electron transport capacity and ATP production in RVLM were reduced, and mitochondria-derived superoxide anion level was augmented. All those detrimental physiological and biochemical events were reversed on microinjection into RVLM of a mobile electron carrier in the mitochondrial respiratory chain, coenzyme Q10; a mitochondria-targeted antioxidant and superoxide anion scavenger, Mito-TEMPO; or an oxidative stress-induced necrotic cell death inhibitor, IM-54. CONCLUSION: We conclude that sustained anoxia and cessation of local blood flow

  11. 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.

  12. Progesterone promotes neuronal differentiation of human umbilical cord mesenchymal stem cells in culture conditions that mimic the brain microenvironment

    Institute of Scientific and Technical Information of China (English)

    Xianying Wang; Honghai Wu; Gai Xue; Yanning Hou

    2012-01-01

    In this study, human umbilical cord mesenchymal stem cells from full-term neonates born by vaginal delivery were cultured in medium containing 150 mg/mL of brain tissue extracts from Sprague-Dawley rats (to mimic the brain microenvironment). Immunocytochemical analysis demonstrated that the cells differentiated into neuron-like cells. To evaluate the effects of progesterone as a neurosteroid on the neuronal differentiation of human umbilical cord mesenchymal stem cells, we cultured the cells in medium containing progesterone (0.1, 1, 10 μM) in addition to brain tissue extracts. Reverse transcription-PCR and flow cytometric analysis of neuron specific enolase-positive cells revealed that the percentages of these cells increased significantly following progesterone treatment, with the optimal progesterone concentration for neuron-like differentiation being 1 μM. These results suggest that progesterone can enhance the neuronal differentiation of human umbilical cord mesenchymal stem cells in culture medium containing brain tissue extracts to mimic the brain microenvironment.

  13. Therapeutics with SPION-labeled stem cells for the main diseases related to brain aging: a systematic review

    Directory of Open Access Journals (Sweden)

    Alvarim LT

    2014-08-01

    Full Text Available Larissa T Alvarim,1,3,* Leopoldo P Nucci,2,* Javier B Mamani,1 Luciana C Marti,1 Marina F Aguiar,1,2 Helio R Silva,1,3 Gisele S Silva,1 Mariana P Nucci-da-Silva,4 Elaine A DelBel,5,6 Lionel F Gamarra1–31Hospital Israelita Albert Einstein, São Paulo, Brazil; 2Universidade Federal de São Paulo, UNIFESP, São Paulo, Brazil; 3Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, Brazil; 4Departamento de Radiologia, Hospital das Clínicas, Universidade de São Paulo, Brazil; 5Universidade de São Paulo-Faculdade de Odontologia de Ribeirão Preto, São Paulo, Brazil; 6NAPNA- Núcleo de Apoio a Pesquisa em Neurociências Aplicadas, São Paulo, Brazil*These authors contributed equally to this workAbstract: The increase in clinical trials assessing the efficacy of cell therapy for structural and functional regeneration of the nervous system in diseases related to the aging brain is well known. However, the results are inconclusive as to the best cell type to be used or the best methodology for the homing of these stem cells. This systematic review analyzed published data on SPION (superparamagnetic iron oxide nanoparticle-labeled stem cells as a therapy for brain diseases, such as ischemic stroke, Parkinson’s disease, amyotrophic lateral sclerosis, and dementia. This review highlights the therapeutic role of stem cells in reversing the aging process and the pathophysiology of brain aging, as well as emphasizing nanotechnology as an important tool to monitor stem cell migration in affected regions of the brain.Keywords: iron oxide, dementia, stem cell, stroke, Parkinson’s disease, sclerosis disease, brain aging

  14. Physiological modulators of Kv3.1 channels adjust firing patterns of auditory brain stem neurons.

    Science.gov (United States)

    Brown, Maile R; El-Hassar, Lynda; Zhang, Yalan; Alvaro, Giuseppe; Large, Charles H; Kaczmarek, Leonard K

    2016-07-01

    Many rapidly firing neurons, including those in the medial nucleus of the trapezoid body (MNTB) in the auditory brain stem, express "high threshold" voltage-gated Kv3.1 potassium channels that activate only at positive potentials and are required for stimuli to generate rapid trains of actions potentials. We now describe the actions of two imidazolidinedione derivatives, AUT1 and AUT2, which modulate Kv3.1 channels. Using Chinese hamster ovary cells stably expressing rat Kv3.1 channels, we found that lower concentrations of these compounds shift the voltage of activation of Kv3.1 currents toward negative potentials, increasing currents evoked by depolarization from typical neuronal resting potentials. Single-channel recordings also showed that AUT1 shifted the open probability of Kv3.1 to more negative potentials. Higher concentrations of AUT2 also shifted inactivation to negative potentials. The effects of lower and higher concentrations could be mimicked in numerical simulations by increasing rates of activation and inactivation respectively, with no change in intrinsic voltage dependence. In brain slice recordings of mouse MNTB neurons, both AUT1 and AUT2 modulated firing rate at high rates of stimulation, a result predicted by numerical simulations. Our results suggest that pharmaceutical modulation of Kv3.1 currents represents a novel avenue for manipulation of neuronal excitability and has the potential for therapeutic benefit in the treatment of hearing disorders.

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

    Science.gov (United States)

    Kim, Jinho

    2016-01-01

    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. PMID:27867930

  16. 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

  17. Recent advances in the involvement of long non-coding RNAs in neural stem cell biology and brain pathophysiology

    Directory of Open Access Journals (Sweden)

    Daphne eAntoniou

    2014-04-01

    Full Text Available Exploration of non-coding genome has recently uncovered a growing list of formerly unknown regulatory long non-coding RNAs (lncRNAs with important functions in stem cell pluripotency, development and homeostasis of several tissues. Although thousands of lncRNAs are expressed in mammalian brain in a highly patterned manner, their roles in brain development have just begun to emerge. Recent data suggest key roles for these molecules in gene regulatory networks controlling neuronal and glial cell differentiation. Analysis of the genomic distribution of genes encoding for lncRNAs indicates a physical association of these regulatory RNAs with transcription factors (TFs with well-established roles in neural differentiation, suggesting that lncRNAs and TFs may form coherent regulatory networks with important functions in neural stem cells (NSCs. Additionally, many studies show that lncRNAs are involved in the pathophysiology of brain-related diseases/disorders. Here we discuss these observations and investigate the links between lncRNAs, brain development and brain-related diseases. Understanding the functions of lncRNAs in NSCs and brain organogenesis could revolutionize the basic principles of developmental biology and neuroscience.

  18. Adenovirus-mediated human brain-derived neurotrophic factor gene-modified bone marrow mesenchymal stem cell transplantation for spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Changsheng Wang; Jianhua Lin; Chaoyang Wu; Rongsheng Chen

    2011-01-01

    Rat bone marrow mesenchymal stem cells expressing brain-derived neurotrophic factor were successfully obtained using a gene transfection method, then intravenously transplanted into rats with spinal cord injury. At 1, 3, and 5 weeks after transplantation, the expression of ??brain-derived neurotrophic factor and neurofilament-200 was upregulated in the injured spinal cord, spinal cord injury was alleviated, and Basso-Beattie-Bresnahan scores of hindlimb motor function were significantly increased. This evidence suggested that intravenous transplantation of adenovirus- mediated brain-derived neurotrophic factor gene-modified rat bone marrow mesenchymal stem cells could play a dual role, simultaneously providing neural stem cells and neurotrophic factors.

  19. Drosophila Brat and Human Ortholog TRIM3 Maintain Stem Cell Equilibrium and Suppress Brain Tumorigenesis by Attenuating Notch Nuclear Transport.

    Science.gov (United States)

    Mukherjee, Subhas; Tucker-Burden, Carol; Zhang, Changming; Moberg, Kenneth; Read, Renee; Hadjipanayis, Costas; Brat, Daniel J

    2016-04-15

    Cancer stem cells exert enormous influence on neoplastic behavior, in part by governing asymmetric cell division and the balance between self-renewal and multipotent differentiation. Growth is favored by deregulated stem cell division, which enhances the self-renewing population and diminishes the differentiation program. Mutation of a single gene in Drosophila, Brain Tumor (Brat), leads to disrupted asymmetric cell division resulting in dramatic neoplastic proliferation of neuroblasts and massive larval brain overgrowth. To uncover the mechanisms relevant to deregulated cell division in human glioma stem cells, we first developed a novel adult Drosophila brain tumor model using brat-RNAi driven by the neuroblast-specific promoter inscuteable Suppressing Brat in this population led to the accumulation of actively proliferating neuroblasts and a lethal brain tumor phenotype. brat-RNAi caused upregulation of Notch signaling, a node critical for self-renewal, by increasing protein expression and enhancing nuclear transport of Notch intracellular domain (NICD). In human glioblastoma, we demonstrated that the human ortholog of Drosophila Brat, tripartite motif-containing protein 3 (TRIM3), similarly suppressed NOTCH1 signaling and markedly attenuated the stem cell component. We also found that TRIM3 suppressed nuclear transport of active NOTCH1 (NICD) in glioblastoma and demonstrated that these effects are mediated by direct binding of TRIM3 to the Importin complex. Together, our results support a novel role for Brat/TRIM3 in maintaining stem cell equilibrium and suppressing tumor growth by regulating NICD nuclear transport. Cancer Res; 76(8); 2443-52. ©2016 AACR.

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

    Science.gov (United States)

    Mouhieddine, Tarek H.; Nokkari, Amaly; Itani, Muhieddine M.; Chamaa, Farah; Bahmad, Hisham; Monzer, Alissar; El-Merahbi, Rabih; Daoud, Georges; Eid, Assaad; Kobeissy, Firas H.; Abou-Kheir, Wassim

    2015-01-01

    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 SH-SY5Y (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. PMID:26635517

  1. 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.

  2. Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells.

    Science.gov (United States)

    Suzuki, Ikuo K; Vanderhaeghen, Pierre

    2015-09-15

    The human brain is arguably the most complex structure among living organisms. However, the specific mechanisms leading to this complexity remain incompletely understood, primarily because of the poor experimental accessibility of the human embryonic brain. Over recent years, technologies based on pluripotent stem cells (PSCs) have been developed to generate neural cells of various types. While the translational potential of PSC technologies for disease modeling and/or cell replacement therapies is usually put forward as a rationale for their utility, they are also opening novel windows for direct observation and experimentation of the basic mechanisms of human brain development. PSC-based studies have revealed that a number of cardinal features of neural ontogenesis are remarkably conserved in human models, which can be studied in a reductionist fashion. They have also revealed species-specific features, which constitute attractive lines of investigation to elucidate the mechanisms underlying the development of the human brain, and its link with evolution.

  3. Identification and culture of neural stem cells isolated from adult rat subventricular zone following fluid percussion brain injury

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To analyze proliferation and differentiation of glial fibrillary acid protein(GFAP)-and nestin-positive(GFAP+/nestin+)cells isolated from the subventricular zone following fluid percussion brain injury to determine whether GFAP+/nestin+ cells exhibit characteristics of neural stem cells.Methods Male Sprague-Dawley rats,aged 12 weeks and weighing 200-250 g,were randomly and evenly assigned to normal control group and model group.In the model group,a rat model of fluid percussion brain injury was es...

  4. The Brain Microenvironment Preferentially Enhances the Radioresistance of CD133+ Glioblastoma Stem-like Cells

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    Muhammad Jamal

    2012-02-01

    Full Text Available Brain tumor xenografts initiated from glioblastoma (GBM CD133+ tumor stem-like cells (TSCs are composed of TSC and non-TSC subpopulations, simulating the phenotypic heterogeneity of GBMs in situ. Given that the discrepancies between the radiosensitivity of GBM cells in vitro and the treatment response of patients suggest a role for the microenvironment in GBM radioresistance, we compared the response of TSCs and non-TSCs irradiated under in vitro and orthotopic conditions. As a measure of radioresponse determined at the individual cell level, γH2AX and 53BP1 foci were quantified in CD133+ cells and their differentiated (CD133- progeny. Under in vitro conditions, no difference was detected between CD133+ and CD133- cells in foci induction or dispersal after irradiation. However, irradiation of orthotopic xenografts initiated from TSCs resulted in the induction of fewer γH2AX and 53BP1 foci in CD133+ cells compared to their CD133- counterparts within the same tumor. Xenograft irradiation resulted in a tumor growth delay of approximately 7 days with a corresponding increase in the percentage of CD133+ cells at 7 days after radiation, which persisted to the onset of neurologic symptoms. These results suggest that, although the radioresponse of TSCs and non-TSCs does not differ under in vitro growth conditions, CD133+ cells are relatively radioresistant under intracerebral growth conditions. Whereas these findings are consistent with the suspected role for TSCs as a determinant of GBM radioresistance, these data also illustrate the dependence of the cellular radioresistance on the brain microenvironment.

  5. 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.

  6. Unmasking the responses of the stem cells and progenitors in the subventricular zone after neonatal and pediatric brain injuries

    Institute of Scientific and Technical Information of China (English)

    Mariano Guardia Clausi; Ekta Kumari; Steven W.Levison

    2016-01-01

    There is great interest in the regenerative potential of the neural stem cells and progenitors that populate the subventricular zone (SVZ). However, a comprehensive understanding of SVZ cell responses to brain in-juries has been hindered by the lack of sensitive approaches to study the cellular composition of this niche. Here we review progress being made in deciphering the cells of the SVZ gleaned from the use of a recently designed lfow cytometry panel that allows SVZ cells to be parsed into multiple subsets of progenitors as well as putative stem cells. We review how this approach has begun to unmask both the heterogeneity of SVZ cells as well as the dynamic shifts in cell populations with neonatal and pediatric brain injuries. We also discuss how lfow cytometric analyses also have begun to reveal how speciifc cytokines, such as Leuke-mia inhibitory factor are coordinating SVZ responses to injury.

  7. 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

  8. Curative effect of transplantation of mesenchymal stem cells transfected with recombinant lentiviral vectors carrying brain-derived neurotrophic factor gene on intracerebral hemorrhage in rats

    Institute of Scientific and Technical Information of China (English)

    任瑞芳

    2013-01-01

    Objective To observe the curative effect of transplantation of mesenchymal stem cells(MSCs) transfected with recombinant lentiviral vectors carrying brain-derived neurotrophic factor(BDNF) gene on intracerebral

  9. Circulating angiotensin II gains access to the hypothalamus and brain stem during hypertension via breakdown of the blood-brain barrier.

    Science.gov (United States)

    Biancardi, Vinicia Campana; Son, Sook Jin; Ahmadi, Sahra; Filosa, Jessica A; Stern, Javier E

    2014-03-01

    Angiotensin II-mediated vascular brain inflammation emerged as a novel pathophysiological mechanism in neurogenic hypertension. However, the precise underlying mechanisms and functional consequences in relation to blood-brain barrier (BBB) integrity and central angiotensin II actions mediating neurohumoral activation in hypertension are poorly understood. Here, we aimed to determine whether BBB permeability within critical hypothalamic and brain stem regions involved in neurohumoral regulation was altered during hypertension. Using digital imaging quantification after intravascularly injected fluorescent dyes and immunohistochemistry, we found increased BBB permeability, along with altered key BBB protein constituents, in spontaneously hypertensive rats within the hypothalamic paraventricular nucleus, the nucleus of the solitary tract, and the rostral ventrolateral medulla, all critical brain regions known to contribute to neurohumoral activation during hypertension. BBB disruption, including increased permeability and downregulation of constituent proteins, was prevented in spontaneously hypertensive rats treated with the AT1 receptor antagonist losartan, but not with hydralazine, a direct vasodilator. Importantly, we found circulating angiotensin II to extravasate into these brain regions, colocalizing with neurons and microglial cells. Taken together, our studies reveal a novel angiotensin II-mediated feed-forward mechanism during hypertension, by which circulating angiotensin II evokes increased BBB permeability, facilitating in turn its access to critical brain regions known to participate in blood pressure regulation.

  10. Stem cell recruitment of newly formed host cells via a successful seduction? Filling the gap between neurogenic niche and injured brain site.

    Directory of Open Access Journals (Sweden)

    Naoki Tajiri

    Full Text Available Here, we report that a unique mechanism of action exerted by stem cells in the repair of the traumatically injured brain involves their ability to harness a biobridge between neurogenic niche and injured brain site. This biobridge, visualized immunohistochemically and laser captured, corresponded to an area between the neurogenic subventricular zone and the injured cortex. That the biobridge expressed high levels of extracellular matrix metalloproteinases characterized initially by a stream of transplanted stem cells, but subsequently contained only few to non-detectable grafts and overgrown by newly formed host cells, implicates a novel property of stem cells. The transplanted stem cells manifest themselves as pathways for trafficking the migration of host neurogenic cells, but once this biobridge is formed between the neurogenic site and the injured brain site, the grafted cells disappear and relinquish their task to the host neurogenic cells. Our findings reveal that long-distance migration of host cells from the neurogenic niche to the injured brain site can be achieved through transplanted stem cells serving as biobridges for initiation of endogenous repair mechanisms. This is the first report of a stem cell-paved "biobridge". Indeed, to date the two major schools of discipline in stem cell repair mechanism primarily support the concept of "cell replacement" and bystander effects of "trophic factor secretion". The present novel observations of a stem cell seducing a host cell to engage in brain repair advances basic science concepts on stem cell biology and extracellular matrix, as well as provokes translational research on propagating this stem cell-paved biobridge beyond cell replacement and trophic factor secretion for the treatment of traumatic brain injury and other neurological disorders.

  11. Stem cell recruitment of newly formed host cells via a successful seduction? Filling the gap between neurogenic niche and injured brain site.

    Science.gov (United States)

    Tajiri, Naoki; Kaneko, Yuji; Shinozuka, Kazutaka; Ishikawa, Hiroto; Yankee, Ernest; McGrogan, Michael; Case, Casey; Borlongan, Cesar V

    2013-01-01

    Here, we report that a unique mechanism of action exerted by stem cells in the repair of the traumatically injured brain involves their ability to harness a biobridge between neurogenic niche and injured brain site. This biobridge, visualized immunohistochemically and laser captured, corresponded to an area between the neurogenic subventricular zone and the injured cortex. That the biobridge expressed high levels of extracellular matrix metalloproteinases characterized initially by a stream of transplanted stem cells, but subsequently contained only few to non-detectable grafts and overgrown by newly formed host cells, implicates a novel property of stem cells. The transplanted stem cells manifest themselves as pathways for trafficking the migration of host neurogenic cells, but once this biobridge is formed between the neurogenic site and the injured brain site, the grafted cells disappear and relinquish their task to the host neurogenic cells. Our findings reveal that long-distance migration of host cells from the neurogenic niche to the injured brain site can be achieved through transplanted stem cells serving as biobridges for initiation of endogenous repair mechanisms. This is the first report of a stem cell-paved "biobridge". Indeed, to date the two major schools of discipline in stem cell repair mechanism primarily support the concept of "cell replacement" and bystander effects of "trophic factor secretion". The present novel observations of a stem cell seducing a host cell to engage in brain repair advances basic science concepts on stem cell biology and extracellular matrix, as well as provokes translational research on propagating this stem cell-paved biobridge beyond cell replacement and trophic factor secretion for the treatment of traumatic brain injury and other neurological disorders.

  12. Neuroanesthesia management of neurosurgery of brain stem tumor requiring neurophysiology monitoring in an iMRI OT setting

    Directory of Open Access Journals (Sweden)

    Sabbagh Abdulrahman

    2009-01-01

    Full Text Available This report describes a rare case of ventrally exophytic pontine glioma describing operative and neuroanesthesia management. The combination of intraoperative neuromonitoring was used. It constituted: Brain stem evoked responses/potentials, Motor EP: recording from cranial nerve supplied muscle, and Sensory EP: Medial/tibial. Excision of the tumor was done with intra-operative magnatic resonance imaging (iMRI, which is considered a new modality.

  13. Repair of spinal cord injury by neural stem cells transfected with brain-derived neurotrophic factor-green fluorescent protein in rats A double effect of stem cells and growth factors

    Institute of Scientific and Technical Information of China (English)

    Yansong Wang; Gang Lü

    2010-01-01

    Brain-derived neurotrophic factor(BDNF)can significantly promote nerve regeneration and repair.High expression of the BDNF-green fluorescent protein(GFP)gene persists for a long time after transfection into neural stem cells.Nevertheless,little is known about the biological characteristics of BDNF-GFP modified nerve stem cells in vivo and their ability to induce BDNF expression or repair spinal cord injury.In the present study,we transplanted BDNF-GFP transgenic neural stem cells into a hemisection model of rats.Rats with BDNF-GFP stem cells exhibited significantly increased BDNF expression and better locomotor function compared with stem cells alone.Cellular therapy with BDNF-GFP transgenic stem cells can improve outcomes better than stem cells alone and may have therapeutic potential for spinal cord injury.

  14. Susceptibility-weighted imaging of the venous networks around the brain stem

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Ming; Lin, Zhong-Xiao; Zhang, Nu [Wenzhou Medical University, Department of Neurosurgery, The 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou (China); Zhang, Xiao-Fen; Qiao, Hui-Huang; Chen, Cheng-Chun [Wenzhou Medical University, Department of Human Anatomy, Wenzhou (China); Ren, Chuan-Gen; Li, Jian-Ce [Wenzhou Medical University, Department of Radiology, The 1nd Affiliated Hospital of Wenzhou Medical University, Wenzhou (China)

    2014-10-18

    The venous network of the brainstem is complex and significant. Susceptibility-weighted imaging (SWI) is a practical technique which is sensitive to veins, especially tiny veins. Our purpose of this study was to evaluate the visualization of the venous network of brainstem by using SWI at 3.0 T. The occurrence rate of each superficial veins of brainstem was evaluated by using SWI on a 3 T MR imaging system in 60 volunteers. The diameter of the lateral mesencephalic vein and peduncular vein were measured by SWI using the reconstructed mIP images in the sagittal view. And the outflow of the veins of brainstem were studied and described according to the reconstructed images. The median anterior pontomesencephalic vein, median anterior medullary vein, peduncular vein, right vein of the pontomesencephalic sulcus, and right lateral anterior pontomesencephalic vein were detected in all the subjects (100 %). The outer diameter of peduncular vein was 1.38 ± 0.26 mm (range 0.8-1.8 mm). The lateral mesencephalic vein was found in 75 % of the subjects and the mean outer diameter was 0.81 ± 0.2 mm (range 0.5-1.2 mm). The inner veins of mesencephalon were found by using SWI. The venous networks around the brain stem can be visualized by SWI clearly. This result can not only provide data for anatomical study, but also may be available for the surgical planning in the infratentorial region. (orig.)

  15. A developmental study of bone conduction auditory brain stem response in infants.

    Science.gov (United States)

    Yang, E Y; Rupert, A L; Moushegian, G

    1987-08-01

    Two studies, vibrator placement and masking, were performed to evaluate the developmental aspect of bone conduction auditory brain stem response (ABR) in human infants. Subject groups included newborns, 1-yr-olds, and adults. In the vibrator studies, ABRs were obtained from placements of the bone conduction vibrator on the frontal, occipital, and temporal bones. Results showed that temporal placements in neonates and 1-yr-olds produce significantly shorter wave V latencies of ABR than frontal or occipital placements. In adults, differences of wave V latencies from various vibrator placements were comparatively small. In the masking studies, ABRs were acquired from vibrator placements at the temporal bone in the presence of ipsilateral air conducted masking noise from the experimental groups. Results showed that interaural attenuations of bone conduction click stimuli are the largest in neonates, somewhat smaller from 1-yr-olds, and the smallest in adults. The findings of this research strongly suggest that temporal placements for bone conduction ABR should be used, in some instances, when testing infants and 1-yr-olds. The results of this study support the proposition that bone conduction ABR is a feasible and reliable diagnostic tool in testing infants.

  16. EphrinB3 restricts endogenous neural stem cell migration after traumatic brain injury.

    Science.gov (United States)

    Dixon, Kirsty J; Mier, Jose; Gajavelli, Shyam; Turbic, Alisa; Bullock, Ross; Turnley, Ann M; Liebl, Daniel J

    2016-11-01

    Traumatic brain injury (TBI) leads to a series of pathological events that can have profound influences on motor, sensory and cognitive functions. Conversely, TBI can also stimulate neural stem/progenitor cell proliferation leading to increased numbers of neuroblasts migrating outside their restrictive neurogenic zone to areas of damage in support of tissue integrity. Unfortunately, the factors that regulate migration are poorly understood. Here, we examine whether ephrinB3 functions to restrict neuroblasts from migrating outside the subventricular zone (SVZ) and rostral migratory stream (RMS). We have previously shown that ephrinB3 is expressed in tissues surrounding these regions, including the overlying corpus callosum (CC), and is reduced after controlled cortical impact (CCI) injury. Our current study takes advantage of ephrinB3 knockout mice to examine the influences of ephrinB3 on neuroblast migration into CC and cortex tissues after CCI injury. Both injury and/or ephrinB3 deficiency led to increased neuroblast numbers and enhanced migration outside the SVZ/RMS zones. Application of soluble ephrinB3-Fc molecules reduced neuroblast migration into the CC after injury and limited neuroblast chain migration in cultured SVZ explants. Our findings suggest that ephrinB3 expression in tissues surrounding neurogenic regions functions to restrict neuroblast migration outside the RMS by limiting chain migration.

  17. Subthreshold K+ Channel Dynamics Interact With Stimulus Spectrum to Influence Temporal Coding in an Auditory Brain Stem Model

    Science.gov (United States)

    Day, Mitchell L.; Doiron, Brent; Rinzel, John

    2013-01-01

    Neurons in the auditory brain stem encode signals with exceptional temporal precision. A low-threshold potassium current, IKLT, present in many auditory brain stem structures and thought to enhance temporal encoding, facilitates spike selection of rapid input current transients through an associated dynamic gate. Whether the dynamic nature of IKLT interacts with the timescales in spectrally rich input to influence spike encoding remains unclear. We examine the general influence of IKLT on spike encoding of stochastic stimuli using a pattern classification analysis between spike responses from a ventral cochlear nucleus (VCN) model containing IKLT, and the same model with the dynamics removed. The influence of IKLT on spike encoding depended on the spectral content of the current stimulus such that maximal IKLT influence occurred for stimuli with power concentrated at frequencies low enough (<500 Hz) to allow IKLT activation. Further, broadband stimuli significantly decreased the influence of IKLT on spike encoding, suggesting that broadband stimuli are not well suited for investigating the influence of some dynamic membrane nonlinearities. Finally, pattern classification on spike responses was performed for physiologically realistic conductance stimuli created from various sounds filtered through an auditory nerve (AN) model. Regardless of the sound, the synaptic input arriving at VCN had similar low-pass power spectra, which led to a large influence of IKLT on spike encoding, suggesting that the subthreshold dynamics of IKLT plays a significant role in shaping the response of real auditory brain stem neurons. PMID:18057115

  18. Scientific and ethical issues related to stem cell research and interventions in neurodegenerative disorders of the brain.

    Science.gov (United States)

    Barker, Roger A; de Beaufort, Inez

    2013-11-01

    Should patients with Parkinson's disease participate in research involving stem cell treatments? Are induced pluripotent stem cells (iPSC) the ethical solution to the moral issues regarding embryonic stem cells? How can we adapt trial designs to best assess small numbers of patients in receipt of invasive experimental therapies? Over the last 20 years there has been a revolution in our ability to make stem cells from different sources and use them for therapeutic gain in disorders of the brain. These cells, which are defined by their capacity to proliferate indefinitely as well as differentiate into selective phenotypic cell types, are viewed as being especially attractive for studying disease processes and for grafting in patients with chronic incurable neurodegenerative disorders of the CNS such as Parkinson's disease (PD). In this review we briefly discuss and summarise where our understanding of stem cell biology has taken us relative to the clinic and patients, before dealing with some of the major ethical issues that work of this nature generates. This includes issues to do with the source of the cells, their ownership and exploitation along with questions about patient recruitment, consent and trial design when they translate to the clinic for therapeutic use.

  19. Activated astrocytes enhance the dopaminergic differentiation of stem cells and promote brain repair through bFGF.

    Science.gov (United States)

    Yang, Fan; Liu, Yunhui; Tu, Jie; Wan, Jun; Zhang, Jie; Wu, Bifeng; Chen, Shanping; Zhou, Jiawei; Mu, Yangling; Wang, Liping

    2014-12-17

    Astrocytes provide neuroprotective effects against degeneration of dopaminergic (DA) neurons and play a fundamental role in DA differentiation of neural stem cells. Here we show that light illumination of astrocytes expressing engineered channelrhodopsin variant (ChETA) can remarkably enhance the release of basic fibroblast growth factor (bFGF) and significantly promote the DA differentiation of human embryonic stem cells (hESCs) in vitro. Light activation of transplanted astrocytes in the substantia nigra (SN) also upregulates bFGF levels in vivo and promotes the regenerative effects of co-transplanted stem cells. Importantly, upregulation of bFGF levels, by specific light activation of endogenous astrocytes in the SN, enhances the DA differentiation of transplanted stem cells and promotes brain repair in a mouse model of Parkinson's disease (PD). Our study indicates that astrocyte-derived bFGF is required for regulation of DA differentiation of the stem cells and may provide a strategy targeting astrocytes for treatment of PD.

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

    Institute of Scientific and Technical Information of China (English)

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

    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 lfuid (2.5–3.0 atm impact force). The injured rats were then administered UC-MSC transplantationvia 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 signiifcantly improved. UC-MSC transplantation combined with HBO therapyfor repair of traumatic brain injury shows better therapeutic effects than monotherapy and signiifcantly promotes recovery of neurological functions.

  1. Reactive astrocytes promote the metastatic growth of breast cancer stem-like cells by activating Notch signalling in brain.

    Science.gov (United States)

    Xing, Fei; Kobayashi, Aya; Okuda, Hiroshi; Watabe, Misako; Pai, Sudha K; Pandey, Puspa R; Hirota, Shigeru; Wilber, Andrew; Mo, Yin-Yuan; Moore, Brian E; Liu, Wen; Fukuda, Koji; Iiizumi, Megumi; Sharma, Sambad; Liu, Yin; Wu, Kerui; Peralta, Elizabeth; Watabe, Kounosuke

    2013-03-01

    Brain metastasis of breast cancer profoundly affects the cognitive and sensory functions as well as morbidity of patients, and the 1 year survival rate among these patients remains less than 20%. However, the pathological mechanism of brain metastasis is as yet poorly understood. In this report, we found that metastatic breast tumour cells in the brain highly expressed IL-1β which then 'activated' surrounding astrocytes. This activation significantly augmented the expression of JAG1 in the astrocytes, and the direct interaction of the reactivated astrocytes and cancer stem-like cells (CSCs) significantly stimulated Notch signalling in CSCs. We also found that the activated Notch signalling in CSCs up-regulated HES5 followed by promoting self-renewal of CSCs. Furthermore, we have shown that the blood-brain barrier permeable Notch inhibitor, Compound E, can significantly suppress the brain metastasis in vivo. These results represent a novel paradigm for the understanding of how metastatic breast CSCs re-establish their niche for their self-renewal in a totally different microenvironment, which opens a new avenue to identify a novel and specific target for the brain metastatic disease.

  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. Study of brain-derived neurotrophic factor gene transgenic neural stem cells in the rat retina

    Institute of Scientific and Technical Information of China (English)

    ZHOU Xue-mei; YUAN Hui-ping; WU Dong-lai; ZHOU Xin-rong; SUN Da-wei; LI Hong-yi; SHAO Zheng-bo

    2009-01-01

    Background Neural stem cells (NSCs) transplantation and gene therapy have been widely investigated for treating the cerebullar and myelonic injuries, however, studies on the ophthalmology are rare. The aim of this study was to investigate the migration and differentiation of brain-derived neurotrophic factor (BDNF) gene transgenic NSCs transplanted into the normal rat retinas. Methods NSCs were cultured and purified in vitro and infected with recombinant retrovirus pLXSN-BDNF and pLXSN respectively, to obtain the BDNF overexpressed NSCs (BDNF-NSCs) and control cells (p-NSCs). The expression of BDNF genes in two transgenic NSCs and untreated NSCs were measured by fluorescent quantitative polymerase chain reaction (FQ-PCR) and enzyme-linked immunosorbent assay (ELISA). BDNF-NSCs and NSCs were infected with adeno-associated viruses-enhanced green fluorescent protein (AAV-EGFP) to track them in vivo and served as donor cells for transplantation into the subretinal space of normal rat retinas, phosphated buffer solution (PBS) served as pseudo transplantation for a negative control. Survival, migration, and differentiation of donor cells in host retinas were observed and analyzed with Heidelberg retina angiograph (HRA) and immunohistochemistry, respectively. Results NSCs were purified successfully by limiting dilution assay. The expression of BDNF gene in BDNF-NSCs was the highest among three groups both at mRNA level tested by FQ-PCR (P<0.05) and at protein level measured by ELISA (P<0.05), which showed that BDNF was overexpressed in BDNF-NSCs. The results of HRA demonstrated that graft cells could survive well and migrate into the host retinas, while the immunohistochemical analysis revealed that transplanted BDNF-NSCs differentiated into neuron more efficiently compared with the control NSCs 2 months after transplantation. Conclusions The seed cells of NSCs highly secreting BDNF were established. BDNF can promote NSCs to migrate and differentiate into neural cells in

  4. Nanoparticle-based CT imaging technique for longitudinal and quantitative stem cell tracking within the brain: application in neuropsychiatric disorders.

    Science.gov (United States)

    Betzer, Oshra; Shwartz, Amit; Motiei, Menachem; Kazimirsky, Gila; Gispan, Iris; Damti, Efrat; Brodie, Chaya; Yadid, Gal; Popovtzer, Rachela

    2014-09-23

    A critical problem in the development and implementation of stem cell-based therapy is the lack of reliable, noninvasive means to image and trace the cells post-transplantation and evaluate their biodistribution, final fate, and functionality. In this study, we developed a gold nanoparticle-based CT imaging technique for longitudinal mesenchymal stem cell (MSC) tracking within the brain. We applied this technique for noninvasive monitoring of MSCs transplanted in a rat model for depression. Our research reveals that cell therapy is a potential approach for treating neuropsychiatric disorders. Our results, which demonstrate that cell migration could be detected as early as 24 h and up to one month post-transplantation, revealed that MSCs specifically navigated and homed to distinct depression-related brain regions. We further developed a noninvasive quantitative CT ruler, which can be used to determine the number of cells residing in a specific brain region, without tissue destruction or animal scarification. This technique may have a transformative effect on cellular therapy, both for basic research and clinical applications.

  5. Tsx produces a long noncoding RNA and has general functions in the germline, stem cells, and brain.

    Directory of Open Access Journals (Sweden)

    Montserrat C Anguera

    2011-09-01

    Full Text Available The Tsx gene resides at the X-inactivation center and is thought to encode a protein expressed in testis, but its function has remained mysterious. Given its proximity to noncoding genes that regulate X-inactivation, here we characterize Tsx and determine its function in mice. We find that Tsx is actually noncoding and the long transcript is expressed robustly in meiotic germ cells, embryonic stem cells, and brain. Targeted deletion of Tsx generates viable offspring and X-inactivation is only mildly affected in embryonic stem cells. However, mutant embryonic stem cells are severely growth-retarded, differentiate poorly, and show elevated cell death. Furthermore, male mice have smaller testes resulting from pachytene-specific apoptosis and a maternal-specific effect results in slightly smaller litters. Intriguingly, male mice lacking Tsx are less fearful and have measurably enhanced hippocampal short-term memory. Combined, our study indicates that Tsx performs general functions in multiple cell types and links the noncoding locus to stem and germ cell development, learning, and behavior in mammals.

  6. 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.

  7. Brain stem gliosarcoma in pediatric patient: a case report; Gliossarcoma de tronco cerebral em paciente pediatrico: relato de caso

    Energy Technology Data Exchange (ETDEWEB)

    Moreira, Roger Klein; Koppe, Daniela; Zignani, Juliana [Rio Grande do Sul Univ., Porto Alegre, RS (Brazil). Faculdade de Medicina; Marconato, Marlon Cesar [Santa Maria Univ., RS (Brazil). Faculdade de Medicina; Abreu, Marcelo; Pitrez, Eduardo; Furtado, Alvaro Porto Alegre [Hospital das Clinicas, Porto Alegre, RS (Brazil). Servico de Radiologia

    2004-02-01

    The authors report a case of a white four year old boy with progressive neurological symptoms due to a brain stem mass lesion identified by computed tomography and magnetic resonance imaging scans. The diagnosis of gliosarcoma was confirmed by histological examination. This rare type of central nervous systems tumor affects mainly patients over 40 year of age and is most commonly supratentorial. Only a few cases of gliosarcoma in children have been reported, particularly int the infratentorial region. The epidemiological data as well as the most frequent computed tomography and magnetic resonance imaging findings are discussed. (author)

  8. TYPE-2 DIABETES MELLITUS AND BRAIN STEM EVOKED RESPONSE AUDIOMETRY: A CASE CONTROL STUDY

    Directory of Open Access Journals (Sweden)

    Praveen S

    2016-01-01

    Full Text Available BACKGROUND AND OBJECTIVE Type-2 Diabetes Mellitus (T2DM causes pathophysiological changes in multiple organ system. The peripheral, autonomic and central neuropathy is known to occur in T2DM, which can be studied electrophysiologically. AIM Present study is aimed to evaluate functional integrity of auditory pathway in T2DM by Brainstem Evoked Response Audiometry (BERA. MATERIAL AND METHOD In the present case control study, BERA was recorded from the scalp of 20 T2DM patients aged 30-65 years and were compared with age matched 20 healthy controls. The BERA was performed using EMG Octopus, Clarity Medical Pvt. Ltd. The latencies of wave I, III, V and Wave I-III, I-V and III-V interpeak latencies of both right and left ear were recorded at 70dBHL. STATISTICAL RESULT AND USE Mean±SD of latencies of wave I, III, V and interpeak latency of I-III, I-V and III-V were estimated of T2DM and healthy controls. The significant differences between the two groups were assessed using unpaired student ‘t’ test for T2DM and control groups using GraphPad QuickCalcs calculator. P value <0.05 was considered to be significant. RESULT In T2DM BERA study revealed statistically significant (p<0.05 prolonged latencies of wave I, III and V in both right (1.81±0.33ms, 3.96±0.32ms, 5.60±0.25ms and left (1.96±0.24ms, 3.79±0.22ms, 5.67±0.25ms ear as compared to controls at 70dB. Wave III-V interpeak latency of left ear (1.87±0.31, 1.85±0.41ms and wave I-III (2.51±0.42ms, 1.96±0.48ms and III-V (2.01±0.43ms, 1.76±0.45ms of right ear was prolonged in diabetic patient as compared to controls, although no significant difference was obtained (p<0.05. INTERPRETATION AND CONCLUSION Increase in absolute latencies and interpeak latencies inT2DM patients suggest involvement of central neuronal axis at the level of brain stem and midbrain.

  9. A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources

    Science.gov (United States)

    Lippmann, Ethan S.; Al-Ahmad, Abraham; Azarin, Samira M.; Palecek, Sean P.; Shusta, Eric V.

    2014-02-01

    Blood-brain barrier (BBB) models are often used to investigate BBB function and screen brain-penetrating therapeutics, but it has been difficult to construct a human model that possesses an optimal BBB phenotype and is readily scalable. To address this challenge, we developed a human in vitro BBB model comprising brain microvascular endothelial cells (BMECs), pericytes, astrocytes and neurons derived from renewable cell sources. First, retinoic acid (RA) was used to substantially enhance BBB phenotypes in human pluripotent stem cell (hPSC)-derived BMECs, particularly through adherens junction, tight junction, and multidrug resistance protein regulation. RA-treated hPSC-derived BMECs were subsequently co-cultured with primary human brain pericytes and human astrocytes and neurons derived from human neural progenitor cells (NPCs) to yield a fully human BBB model that possessed significant tightness as measured by transendothelial electrical resistance (~5,000 Ωxcm2). Overall, this scalable human BBB model may enable a wide range of neuroscience studies.

  10. Brain-derived neurotrophic factor induces neuron-like cellular differentiation of mesenchymal stem cells derived from human umbilical cord blood cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Lei Chen; Guozhen Hui; Zhongguo Zhang; Bing Chen; Xiaozhi Liu; Zhenlin Liu; Hongliang Liu; Gang Li; Zhiguo Su; Junfei Wang

    2011-01-01

    Human umbilical cord blood was collected from full-term deliveries scheduled for cesarean section. Mononuclear cells were isolated, amplified and induced as mesenchymal stem cells. Isolated mesenchymal stem cells tested positive for the marker CD29, CD44 and CD105 and negative for typical hematopoietic and endothelial markers. Following treatment with neural induction medium containing brain-derived neurotrophic factor for 7 days, the adherent cells exhibited neuron-like cellular morphology. Immunohistochemical staining and reverse transcription-PCR revealed that the induced mesenchymal stem cells expressed the markers for neuron-specific enolase and neurofilament. The results demonstrated that human umbilical cord blood-derived mesenchymal stem cells can differentiate into neuron-like cells induced by brain-derived neurotrophic factor in vitro.

  11. 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

    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...

  12. β-Amyloid precursor protein: function in stem cell development and Alzheimer's disease brain.

    Science.gov (United States)

    Small, David H; Hu, Yanling; Bolós, Marta; Dawkins, Edgar; Foa, Lisa; Young, Kaylene M

    2014-01-01

    Stem cell therapy may be a suitable approach for the treatment of many neurodegenerative diseases. However, one major impediment to the development of successful cell-based therapies is our limited understanding of the mechanisms that instruct neural stem cell behaviour, such as proliferation and cell fate specification. The β-amyloid precursor protein (APP) of Alzheimer's disease (AD) may play an important role in neural stem cell proliferation and differentiation. Our recent work shows that in vitro, APP stimulates neural stem or progenitor cell proliferation and neuronal differentiation. The effect on proliferation is mediated by an autocrine factor that we have identified as cystatin C. As cystatin C expression is also reported to inhibit the development of amyloid pathology in APP transgenic mice, our finding has implications for the possible use of cystatin C for the therapy of AD.

  13. Brain, Behavior, and Immunity: Biobehavioral influences on recovery following hematopoietic stem cell transplantation

    Science.gov (United States)

    Review of hematopoietic stem cell transplantation and its potential “window of opportunity” during which interventions targeting stress-related behavioral factors can influence the survival, health, and well-being of recipients.

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

    Science.gov (United States)

    Castillo-Melendez, Margie; Yawno, Tamara; Jenkin, Graham; Miller, Suzanne L

    2013-10-24

    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 teratomas, 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 (EPCs) and mesenchymal stem cells (MSCs), and how immunomodulation and anti-inflammatory properties are principal mechanisms of action that are common to these cells, and which in turn may ameliorate the cerebral hypoxia and inflammation that are final pathways in the pathogenesis of perinatal brain

  15. 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

  16. Progress and prospects in neurorehabilitation: clinical applications of stem cells and brain-computer interface for spinal cord lesions.

    Science.gov (United States)

    Gongora, Mariana; Peressutti, Caroline; Machado, Sergio; Teixeira, Silmar; Velasques, Bruna; Ribeiro, Pedro

    2013-04-01

    Spinal cord injury (SCI) is a disease that affects millions of people worldwide, causing a temporary or permanent impairment of neuromotor functions. Mostly associated to traumatic lesions, but also to other forms of disease, the appropriate treatment is still unsure. In this review, several ongoing studies are presented that aim to provide methods of prevention that ensure quality of life, and rehabilitation trends to patients who suffer from this injury. Stem cell research, highlighted in this review, seeks to reduce damage caused to the tissue, as also provide spinal cord regeneration through the application of several types of stem cells. On the other hand, research using brain-computer interface (BCI) technology proposes the development of interfaces based on the interaction of neural networks with artificial tools to restore motor control and full mobility of the injured area. PubMed, MEDLINE and SciELO data basis analyses were performed to identify studies published from 2000 to date, which describe the link between SCI with stem cells and BCI technology.

  17. 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.

  18. Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach.

    Science.gov (United States)

    Nih, Lina R; Moshayedi, Pouria; Llorente, Irene L; Berg, Andrew R; Cinkornpumin, Jessica; Lowry, William E; Segura, Tatiana; Carmichael, S Thomas

    2017-02-01

    This article presents data related to the research article "Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain" (P. Moshayedi, L.R. Nih, I.L. Llorente, A.R. Berg, J. Cinkornpumin, W.E. Lowry et al., 2016) [1] and focuses on the biocompatibility aspects of the hydrogel, including its stiffness and the inflammatory response of the transplanted organ. We have developed an injectable hyaluronic acid (HA)-based hydrogel for stem cell culture and transplantation, to promote brain tissue repair after stroke. This 3D biomaterial was engineered to bind bioactive signals such as adhesive motifs, as well as releasing growth factors while supporting cell growth and tissue infiltration. We used a Design of Experiment approach to create a complex matrix environment in vitro by keeping the hydrogel platform and cell type constant across conditions while systematically varying peptide motifs and growth factors. The optimized HA hydrogel promoted survival of encapsulated human induced pluripotent stem cell derived-neural progenitor cells (iPS-NPCs) after transplantation into the stroke cavity and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. The highlights of this article include: (1) Data of cell and bioactive signals addition on the hydrogel mechanical properties and growth factor diffusion, (2) the use of a design of Experiment (DOE) approach (M.W. 2 Weible and T. Chan-Ling, 2007) [2] to select multi-factorial experimental conditions, and (3) Inflammatory response and cell survival after transplantation.

  19. Distribution of secretoneurin-like immunoreactivity in comparison with that of substance P in the human brain stem.

    Science.gov (United States)

    Marksteiner, J; Saria, A; Hinterhuber, H

    1994-10-01

    Secretoneurin is a peptide of 33 amino acids generated in the brain by proteolytic processing of secretogranin II which is a member of the chromogranin/secretogranin family. The distribution of this newly characterized peptide was investigated by immunocytochemistry in the human brain stem. The staining pattern of secretoneurin-like immunoreactivity was compared with that of substance P in adjacent sections. Secretoneurin-like immunoreactivity appeared mainly in dot- and fiber-like structures with densities varying from low to very high. Only a low number of secretoneurin-immunoreactive perikarya was found. Pericellular staining of both secretoneurin-immunopositive and immunonegative cells was frequently observed in the area of the central gray, in the reticular formation and in the solitary nuclear complex. The medial part of the substantia nigra pars reticulata, the nucleus interpeduncularis, the area of the central gray, the raphe complex and the inferior olive displayed a high density of secretoneurin-like immunoreactivity. Furthermore, a very prominent staining was found in the medial, dorsal and gelatinous subnuclei of the solitary tract and the dorsal motor nucleus of vagus. The substantia gelatinosa of the caudal trigeminal nucleus and spinal cord were also very strongly secretoneurin-immunopositive. The staining patterns of secretoneurin- and substance P-like immunoreactivities were to a certain extent overlapping in several areas. The highest degree of coincidence was found in the substantia gelatinosa. This study demonstrated that secretoneurin is distinctly distributed in the human brain stem. Its distributional pattern indicates a role particularly in the modulation of afferent pain transmission and in the regulation of autonomic functions.

  20. Detection of neural stem cells function in rats with traumatic brain injury by manganese-enhanced magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    TANG Hai-liang; SUN Hua-ping; WU Xing; SHA Hong-ying; FENG Xiao-yuan; ZHU Jian-hong

    2011-01-01

    Background Previously we had successfully tracked adult human neural stem cells (NSCs) labeled with superparamagnetic iron oxide particles (SPIOs) in host human brain after transplantation In vivo non-invasively by magnetic resonance imaging (MRI). However, the function of the transplanted NSCs could not be evaluated by the method. In the study, we applied manganese-enhanced MRI (ME-MRI) to detect NSCs function after implantation in brain of rats with traumatic brain injury (TBI) In vivo.Methods Totally 40 TBI rats were randomly divided into 4 groups with 10 rats in each group. In group 1, the TBI rats did not receive NSCs transplantation. MnCl2-4H2O was intravenously injected, hyperosmolar mannitol was delivered to disrupt rightside blood brain barrier, and its contralateral forepaw was electrically stimulated. In group 2, the TBI rats received NSCs (labeled with SPIO) transplantation, and the ME-MRI procedure was same to group 1. In group 3, the TBI rats received NSCs (labeled with SPIO) transplantation, and the ME-MRI procedure was same to group 1, but diltiazem was introduced during the electrical stimulation period. In group 4, the TBI rats received phosphate buffered saline (PBS) injection, and the ME-MRI procedure was same to group 1.Results Hyperintense signals were detected by ME-MRI in the cortex areas associated with somatosensory in TBI rats of group 2. These signals, which could not be induced in TBI rats of groups 1 and 4, disappeared when diltiazem was introduced in TBI rats of group 3.Conclusion In this initial study, we mapped implanted NSCs activity and its functional participation within local brain area in TBI rats by ME-MRI technique, paving the way for further pre-clinical research.

  1. c-myc and N-myc promote active stem cell metabolism and cycling as architects of the developing brain.

    Science.gov (United States)

    Wey, Alice; Knoepfler, Paul S

    2010-06-01

    myc genes are associated with a wide variety of human cancers including most types of nervous system tumors. While the mechanisms by which myc overexpression causes tumorigenesis are multifaceted and have yet to be clearly elucidated, they are at least in part related to endogenous myc function in normal cells. Knockout (KO) of either c-myc or N-myc genes in neural stem and precursor cells (NSC) driven by nestin-cre impairs mouse brain growth and mutation of N-myc also causes microcephaly in humans in Feingold Syndrome. To further define myc function in NSC and nervous system development, we created a double KO (DKO) for c- and N-myc using nestin-cre. The DKO mice display profoundly impaired overall brain growth associated with decreased cell cycling and migration of NSC, which are strikingly decreased in number. The DKO brain also exhibits specific changes in gene expression including downregulation of genes involved in protein and nucleotide metabolism, mitosis, and chromatin structure as well as upregulation of genes associated with differentiation. Together these data support a model of nervous system tumorigenesis in which excess myc aberrantly locks in a developmentally active chromatin state characterized by overactive cell cycling, and metabolism as well as blocked differentiation.

  2. Evolution of brain-derived neurotrophic factor levels after autologous hematopietic stem cell transplantation in multiple sclerosis.

    Science.gov (United States)

    Blanco, Y; Saiz, A; Costa, M; Torres-Peraza, J F; Carreras, E; Alberch, J; Jaraquemada, D; Graus, F

    A neuroprotective role of inflammation has been suggested based on that immune cells are the main source of brain-derived neurotrophic factor (BDNF). We investigated the 3-year evolution of BDNF levels in serum, CSF and culture supernatant of peripheral blood mononuclear cells (PBMC), unstimulated and stimulated with anti-CD3 and soluble anti-CD28 antibodies, in 14 multiple sclerosis patients who underwent an autologous hematopoietic stem cell transplantation (AHSCT). BDNF levels were correlated with previously reported MRI measures that showed a reduction of T2 lesion load and increased brain atrophy, mainly at first year post-transplant. A significant decrease of serum BDNF levels was seen at 12 months post-transplant. BDNF values were found significantly lower in stimulated but not in unstimulated PBMC supernatants during the follow-up, supporting that AHSCT may induce a down-regulation of BDNF production. The only significant correlation was found between CSF BDNF levels and T2 lesion load before and 1 year after AHSCT, suggesting that BDNF reflects the past and ongoing inflammatory activity and demyelination of these highly active patients. Our study suggests that AHSCT can reduce BDNF levels to values associated with lower activity. This decrease does not seem to correlate with the brain atrophy measures observed in the MRI.

  3. 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.

  4. Interplay between brain stem angiotensins and monocyte chemoattractant protein-1 as a novel mechanism for pressor response after ischemic stroke.

    Science.gov (United States)

    Chang, Alice Y W; Li, Faith C H; Huang, Chi-Wei; Wu, Julie C C; Dai, Kuang-Yu; Chen, Chang-Han; Li, Shau-Hsuan; Su, Chia-Hao; Wu, Re-Wen

    2014-11-01

    Pressor response after stroke commonly leads to early death or susceptibility to stroke recurrence, and detailed mechanisms are still lacking. We assessed the hypothesis that the renin-angiotensin system contributes to pressor response after stroke by differential modulation of the pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) in the rostral ventrolateral medulla (RVLM), a key brain stem site that maintains blood pressure. We also investigated the beneficial effects of a novel renin inhibitor, aliskiren, against stroke-elicited pressor response. Experiments were performed in male adult Sprague-Dawley rats. Stroke induced by middle cerebral artery occlusion elicited significant pressor response, accompanied by activation of angiotensin II (Ang II)/type I receptor (AT1R) and AT2R signaling, depression of Ang-(1-7)/MasR and Ang IV/AT4R cascade, alongside augmentation of MCP-1/C-C chemokine receptor 2 (CCR2) signaling and neuroinflammation in the RVLM. Stroke-elicited pressor response was significantly blunted by antagonism of AT1R, AT2R or MCP-1/CCR2 signaling, and eliminated by applying Ang-(1-7) or Ang IV into the RVLM. Furthermore, stroke-activated MCP-1/CCR2 signaling was enhanced by AT1R and AT2R activation, and depressed by Ang-(1-7)/MasR and Ang IV/AT4R cascade. Aliskiren inhibited stroke-elicited pressor response via downregulating MCP-1/CCR2 activity and reduced neuroinflammation in the RVLM; these effects were potentiated by Ang-(1-7) or Ang IV. We conclude that whereas Ang II/AT1R or Ang II/AT2R signaling in the brain stem enhances, Ang-(1-7)/MasR or Ang IV/AT4R antagonizes pressor response after stroke by differential modulations of MCP-1 in the RVLM. Furthermore, combined administration of aliskiren and Ang-(1-7) or Ang IV into the brain stem provides more effective amelioration of stroked-induced pressor response.

  5. Neural Stem Cell Delivery of Therapeutic Antibodies to Treat Breast Cancer Brain Metastases

    Science.gov (United States)

    2009-10-01

    and Engineering Neural Stem Cells for Delivery of Genetically Encoded 259 References 1. Snyder, EY., Deichter, DL., Walsh, C., Arnold- Aldea , S...acquired with a Zeiss Axio Imager M1m microscope equipped with a digital camera, using 10x or 20x air objectives. Digital images were analyzed using

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

    NARCIS (Netherlands)

    Berkmortel, F. van den; Gidding, C.E.M.; Kanter, M. De; 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

  7. 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.

  8. 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.

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

    Science.gov (United States)

    Kosi, Nina; Alić, Ivan; Kolačević, Matea; Vrsaljko, Nina; Jovanov Milošević, Nataša; Sobol, Margarita; Philimonenko, Anatoly; Hozák, Pavel; Gajović, Srećko; Pochet, Roland; Mitrečić, Dinko

    2015-02-09

    The nucleolar protein 2 gene encodes a protein specific for the nucleolus. It is assumed that it plays a role in the synthesis of ribosomes and regulation of the cell cycle. Due to its link to cell proliferation, higher expression of Nop2 indicates a worse tumor prognosis. In this work we used Nop2(gt1gaj) gene trap mouse strain. While lethality of homozygous animals suggested a vital role of this gene, heterozygous animals allowed the detection of expression of Nop2 in various tissues, including mouse brain. Histochemistry, immunohistochemistry and immunoelectron microscopy techniques, applied to a mature mouse brain, human brain and on mouse neural stem cells revealed expression of Nop2 in differentiating cells, including astrocytes, as well as in mature neurons. Nop2 was detected in various regions of mouse and human brain, mostly in large pyramidal neurons. In the human, Nop2 was strongly expressed in supragranular and infragranular layers of the somatosensory cortex and in layer III of the cingulate cortex. Also, Nop2 was detected in CA1 and the subiculum of the hippocampus. Subcellular analyses revealed predominant location of Nop2 within the dense fibrillar component of the nucleolus. To test if Nop2 expression correlates to cell proliferation occurring during tissue regeneration, we induced strokes in mice by middle cerebral artery occlusion. Two weeks after stroke, the number of Nop2/nestin double positive cells in the region affected by ischemia and the periventricular zone substantially increased. Our findings suggest a newly discovered role of Nop2 in both mature neurons and in cells possibly involved in the regeneration of nervous tissue.

  10. Effects of root and stem extracts of Asparagus cochinchinensis on biochemical indicators related to aging in the brain and liver of mice.

    Science.gov (United States)

    Xiong, Dasheng; Yu, Long-Xi; Yan, Xiao; Guo, Chunqiu; Xiong, Ying

    2011-01-01

    Asparagus cochinchinensis is a traditional Chinese medicine used for treating lung and spleen-related diseases. In this study, we compared the medicinal effects of A. cochinchinensis root and stem extracts on the activity of superoxide dismutase (SOD), the content of malonaldehyde (MDA) and total protein content in the brain, liver and plasma of mice. Polysaccharides and aqueous extracts of the roots significantly increased the spleen index and the SOD activity but reduced the MDA content and slowed down the aging process. In contrast, feeding with the stem extracts significantly reduced the SOD activity and increased the MDA accumulation in the brain and liver of mice, suggesting that the stem extracts may not be appropriate for treating aging-related diseases.

  11. 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......, and control of heart beat. Here we show that the rostral compact formation's ambiguus neurons, which control the esophageal phase of swallowing, display calcium-dependent plateau potentials in response to tetanic orthodromic stimulation or current injection. Whole cell recordings were made from visualized...... neurons in the rostral nucleus ambiguus using a slice preparation from the newborn mouse. Biocytin-labeling revealed dendritic trees with pronounced rostrocaudal orientations confined to the nucleus ambiguus, a morphological profile matching that of vagal motoneurons projecting to the esophagus. Single...

  12. 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

    1. To extend the classification of respiratory neurons based on active membrane properties and discharge patterns to include responses to respiratory modulators, we have studied the effect of thyrotropin-releasing hormone (TRH, 1-5 microM) on the spontaneous respiratory-related neural activity...... 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...... 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...

  13. 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

    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...... 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...... (means +/- SD, n = 50). Based on the electroresponsive properties and membrane potential trajectories throughout the respiratory cycle, three types of inspiratory neurons could be distinguished. 3. Type-1 neurons were spiking in the interval between the inspiratory potentials (n = 9) or silent...

  14. Evaluation of auditory brain-stem evoked response in middle: Aged type 2 diabetes mellitus with normal hearing subjects

    Directory of Open Access Journals (Sweden)

    Debadatta Mahallik

    2014-01-01

    Full Text Available Background: Diabetes mellitus (DM is commonly metabolic disorders of carbohydrate in which blood glucose levels are abnormally high due to relative or absolute insulin deficiency. In addition, it is characterized by abnormal metabolism of fat, protein resulting from insulin deficit or insulin action, or both. There are two broad categories of DM are designated as type 1 and type 2. Type 2 diabetes is due to predominantly insulin resistance with relative insulin deficiency noninsulin-dependent DM. Type 2 diabetes is much more common than insulin-dependent DM. Objectives: The aim of this study was to assess, if there is any abnormality in neural conduction in auditory brain-stem pathway in type 2 DM patients having normal hearing sensitivity when compared to age-matched healthy populations. Materials and Methods: This study included middle - aged 25 subjects having normal hearing with diabetes type 2 mellitus. All were submitted to the full audiological history taking, otological examination, basic audiological evaluation and auditory brain-stem response audiometry which was recorded in both ears, followed by calculation of the absolute latencies of wave I, III and V, as well as interpeak latencies I-III, III-V, I-V. Results: Type 2 DM patients showed significant prolonged absolute latencies of I, III (P = 0.001 and interpeak latencies I-III, III-V and I-V in left ear (P = 0.001 and absolute latencies of I, V (P = 0.001, interpeak latencies III-V was statistically significant in right ear. Conclusions: The prolonged absolute latencies and interpeak latencies suggests abnormal neural firing synchronization or in the transmission in the auditory pathways in normal hearing type 2 diabetes mellitus patients.

  15. 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.

  16. Distribution and localization of fibroblast growth factor-8 in rat brain and nerve cells during neural stem/progenitor cell differentiation

    Institute of Scientific and Technical Information of China (English)

    Jiang Lu; Dongsheng Li; Kehuan Lu

    2012-01-01

    The present study explored the distribution and localization of fibroblast growth factor-8 and its potential receptor,fibroblast growth factor receptor-3,in adult rat brain in vivo and in nerve cells during differentiation of neural stem/progenitor cells in vitro.Immunohistochemistry was used to examine the distribution of fibroblast growth factor-8 in adult rat brain in vivo.Localization of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in cells during neural stem/progenitor cell differentiation in vitro was detected by immunofluorescence.Flow cytometry and immunofluorescence were used to evaluate the effect of an anti-fibroblast growth factor-8 antibody on neural stem/progenitor cell differentiation and expansion in vitro.Results from this study confirmed that fibroblast growth factor-8 was mainly distributed in adult midbrain,namely the substantia nigra,compact part,dorsal tier,substantia nigra and reticular part,but was not detected in the forebrain comprising the caudate putamen and striatum.Unusual results were obtained in retrosplenial locations of adult rat brain.We found that fibroblast growth factor-8 and fibroblast growth factor receptor-3 were distributed on the cell membrane and in the cytoplasm of nerve cells using immunohistochemistry and immunofluorescence analyses.We considered that the distribution of fibroblast growth factor-8 and fibroblast growth factor receptor-3 in neural cells corresponded to the characteristics of fibroblast growth factor-8,a secretory factor.Addition of an anti-fibroblast growth factor-8 antibody to cultures significantly affected the rate of expansion and differentiation of neural stem/progenitor cells.In contrast,addition of recombinant fibroblast growth factor-8 to differentiation medium promoted neural stem/progenitor cell differentiation and increased the final yields of dopaminergic neurons and total neurons.Our study may help delineate the important roles of fibroblast growth factor-8 in brain

  17. SU-E-T-493: Analysis of the Impact of Range and Setup Uncertainties On the Dose to Brain Stem and Whole Brain in the Passively Scattered Proton Therapy Plans

    Energy Technology Data Exchange (ETDEWEB)

    Sahoo, N; Zhu, X; Zhang, X; Poenisch, F; Li, H; Wu, R; Lii, M; Umfleet, W; Gillin, M; Mahajan, A; Grosshans, D [MD Anderson Cancer Ctr., Houston, TX (United States)

    2014-06-01

    Purpose: To quantify the impact of range and setup uncertainties on various dosimetric indices that are used to assess normal tissue toxicities of patients receiving passive scattering proton beam therapy (PSPBT). Methods: Robust analysis of sample treatment plans of six brain cancer patients treated with PSPBT at our facility for whom the maximum brain stem dose exceeded 5800 CcGE were performed. The DVH of each plan was calculated in an Eclipse treatment planning system (TPS) version 11 applying ±3.5% range uncertainty and ±3 mm shift of the isocenter in x, y and z directions to account for setup uncertainties. Worst-case dose indices for brain stem and whole brain were compared to their values in the nominal plan to determine the average change in their values. For the brain stem, maximum dose to 1 cc of volume, dose to 10%, 50%, 90% of volume (D10, D50, D90) and volume receiving 6000, 5400, 5000, 4500, 4000 CcGE (V60, V54, V50, V45, V40) were evaluated. For the whole brain, maximum dose to 1 cc of volume, and volume receiving 5400, 5000, 4500, 4000, 3000 CcGE (V54, V50, V45, V40 and V30) were assessed. Results: The average change in the values of these indices in the worst scenario cases from the nominal plan were as follows. Brain stem; Maximum dose to 1 cc of volume: 1.1%, D10: 1.4%, D50: 8.0%, D90:73.3%, V60:116.9%, V54:27.7%, V50: 21.2%, V45:16.2%, V40:13.6%,Whole brain; Maximum dose to 1 cc of volume: 0.3%, V54:11.4%, V50: 13.0%, V45:13.6%, V40:14.1%, V30:13.5%. Conclusion: Large to modest changes in the dosiemtric indices for brain stem and whole brain compared to nominal plan due to range and set up uncertainties were observed. Such potential changes should be taken into account while using any dosimetric parameters for outcome evaluation of patients receiving proton therapy.

  18. Engineered HA hydrogel for stem cell transplantation in the brain: Biocompatibility data using a design of experiment approach

    Directory of Open Access Journals (Sweden)

    Lina R. Nih

    2017-02-01

    Full Text Available This article presents data related to the research article “Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain” (P. Moshayedi, L.R. Nih, I.L. Llorente, A.R. Berg, J. Cinkornpumin, W.E. Lowry et al., 2016 [1] and focuses on the biocompatibility aspects of the hydrogel, including its stiffness and the inflammatory response of the transplanted organ. We have developed an injectable hyaluronic acid (HA-based hydrogel for stem cell culture and transplantation, to promote brain tissue repair after stroke. This 3D biomaterial was engineered to bind bioactive signals such as adhesive motifs, as well as releasing growth factors while supporting cell growth and tissue infiltration. We used a Design of Experiment approach to create a complex matrix environment in vitro by keeping the hydrogel platform and cell type constant across conditions while systematically varying peptide motifs and growth factors. The optimized HA hydrogel promoted survival of encapsulated human induced pluripotent stem cell derived-neural progenitor cells (iPS-NPCs after transplantation into the stroke cavity and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. The highlights of this article include: (1 Data of cell and bioactive signals addition on the hydrogel mechanical properties and growth factor diffusion, (2 the use of a design of Experiment (DOE approach (M.W. 2 Weible and T. Chan-Ling, 2007 [2] to select multi-factorial experimental conditions, and (3 Inflammatory response and cell survival after transplantation.

  19. Mesenchymal Stem Cells Expressing Brain-Derived Neurotrophic Factor Enhance Endogenous Neurogenesis in an Ischemic Stroke Model

    Directory of Open Access Journals (Sweden)

    Chang Hyun Jeong

    2014-01-01

    Full Text Available Numerous studies have reported that mesenchymal stem cells (MSCs can ameliorate neurological deficits in ischemic stroke models. Among the various hypotheses that have been suggested to explain the therapeutic mechanism underlying these observations, neurogenesis is thought to be critical. To enhance the therapeutic benefits of human bone marrow-derived MSCs (hBM-MSCs, we efficiently modified hBM-MSCs by introduction of the brain-derived neurotrophic factor (BDNF gene via adenoviral transduction mediated by cell-permeable peptides and investigated whether BDNF-modified hBM-MSCs (MSCs-BDNF contributed to functional recovery and endogenous neurogenesis in a rat model of middle cerebral artery occlusion (MCAO. Transplantation of MSCs induced the proliferation of 5-bromo-2′-deoxyuridine (BrdU- positive cells in the subventricular zone. Transplantation of MSCs-BDNF enhanced the proliferation of endogenous neural stem cells more significantly, while suppressing cell death. Newborn cells differentiated into doublecortin (DCX- positive neuroblasts and Neuronal Nuclei (NeuN- positive mature neurons in the subventricular zone and ischemic boundary at higher rates in animals with MSCs-BDNF compared with treatment using solely phosphate buffered saline (PBS or MSCs. Triphenyltetrazolium chloride staining and behavioral analysis revealed greater functional recovery in animals with MSCs-BDNF compared with the other groups. MSCs-BDNF exhibited effective therapeutic potential by protecting cell from apoptotic death and enhancing endogenous neurogenesis.

  20. Mesenchymal stem cells expressing brain-derived neurotrophic factor enhance endogenous neurogenesis in an ischemic stroke model.

    Science.gov (United States)

    Jeong, Chang Hyun; Kim, Seong Muk; Lim, Jung Yeon; Ryu, Chung Heon; Jun, Jin Ae; Jeun, Sin-Soo

    2014-01-01

    Numerous studies have reported that mesenchymal stem cells (MSCs) can ameliorate neurological deficits in ischemic stroke models. Among the various hypotheses that have been suggested to explain the therapeutic mechanism underlying these observations, neurogenesis is thought to be critical. To enhance the therapeutic benefits of human bone marrow-derived MSCs (hBM-MSCs), we efficiently modified hBM-MSCs by introduction of the brain-derived neurotrophic factor (BDNF) gene via adenoviral transduction mediated by cell-permeable peptides and investigated whether BDNF-modified hBM-MSCs (MSCs-BDNF) contributed to functional recovery and endogenous neurogenesis in a rat model of middle cerebral artery occlusion (MCAO). Transplantation of MSCs induced the proliferation of 5-bromo-2'-deoxyuridine (BrdU-) positive cells in the subventricular zone. Transplantation of MSCs-BDNF enhanced the proliferation of endogenous neural stem cells more significantly, while suppressing cell death. Newborn cells differentiated into doublecortin (DCX-) positive neuroblasts and Neuronal Nuclei (NeuN-) positive mature neurons in the subventricular zone and ischemic boundary at higher rates in animals with MSCs-BDNF compared with treatment using solely phosphate buffered saline (PBS) or MSCs. Triphenyltetrazolium chloride staining and behavioral analysis revealed greater functional recovery in animals with MSCs-BDNF compared with the other groups. MSCs-BDNF exhibited effective therapeutic potential by protecting cell from apoptotic death and enhancing endogenous neurogenesis.

  1. 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

    We examined the effects of interleukin-6 (IL-6) deficiency on brain inflammation and the accompanying bone marrow (BM) leukopoiesis and spleen immune reaction after systemic administration of a niacin antagonist, 6-aminonicotinamide (6-AN), which causes both astroglial degeneration/cell death...... 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...... astrocytosis encircled gray matter areas containing astroglial degeneration/cell death, which were infiltrated by several macrophages and some T-lymphocytes. Reactive astrocytes and a few macrophages increased significantly the antioxidants metallothionein-I+II (MT-I+II) and moderately the MT-III isoform. In 6...

  2. 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

  3. Characterization of neural stem/progenitor cells expressing VEGF and its receptors in the subventricular zone of newborn piglet brain.

    Science.gov (United States)

    Ara, Jahan; Fekete, Saskia; Zhu, Anli; Frank, Melissa

    2010-09-01

    Neural stem/progenitor cell (NSP) biology and neurogenesis in adult central nervous system (CNS) are important both towards potential future therapeutic applications for CNS repair, and for the fundamental function of the CNS. In the present study, we report the characterization of NSP population from subventricular zone (SVZ) of neonatal piglet brain using in vivo and in vitro systems. We show that the nestin and vimentin-positive neural progenitor cells are present in the SVZ of the lateral ventricles of neonatal piglet brain. In vitro, piglet NSPs proliferated as neurospheres, expressed the typical protein of neural progenitors, nestin and a range of well-established neurodevelopmental markers. Upon dissociation and subculture, piglet NSPs differentiated into neurons and glial cells. Clonal analysis demonstrates that piglet NSPs are multipotent and retain the capacity to generate both glia and neurons. These cells expressed VEGF, VEGFR1, VEGFR2 and Neuropilin-1 and -2 mRNAs. Real time PCR revealed that SVZ NSPs from newborn piglet expressed total VEGF and all VEGF splice variants. These findings show that piglet NSPs may be helpful to more effectively design growth factor based strategies to enhance endogenous precursor cells for cell transplantation studies potentially leading to the application of this strategy in the nervous system disease and injury.

  4. Reduced 5-HT(1B) receptor binding in the dorsal brain stem after cognitive behavioural therapy of major depressive disorder.

    Science.gov (United States)

    Tiger, Mikael; Rück, Christian; Forsberg, Anton; Varrone, Andrea; Lindefors, Nils; Halldin, Christer; Farde, Lars; Lundberg, Johan

    2014-08-30

    Major depression is a significant contributor to the global burden of disease, and its pathophysiology is largely unknown. The serotonin hypothesis is, however, the model with most supporting data, although the details are only worked out to some extent. Recent clinical imaging measurements indeed imply a role in major depressive disorder (MDD) for the inhibitory serotonin autoreceptor 5-hydroxytryptamine1B (5-HT1B). The aim of the current study was to examine 5-HT1B receptor binding in the brain of MDD patients before and after psychotherapy. Ten patients with an ongoing untreated moderate depressive episode were examined with positron emission tomography (PET) and the 5-HT1B receptor selective radioligand [(11)C]AZ10419369, before and after treatment with internet-based cognitive behavioural therapy. All of the patients examined responded to treatment, and 70% were in remission by the time of the second PET measurement. A statistically significant 33% reduction of binding potential (BPND) was found in the dorsal brain stem (DBS) after treatment. No other significant changes in BPND were found. The DBS contains the raphe nuclei, which regulate the serotonin system. This study gives support for the importance of serotonin and the 5-HT1B receptor in the biological response to psychological treatment of MDD.

  5. Functional recovery after transplantation of neural stem cells modified by brain-derived neurotrophic factor in rats with cerebral ischaemia.

    Science.gov (United States)

    Zhu, J M; Zhao, Y Y; Chen, S D; Zhang, W H; Lou, L; Jin, X

    2011-01-01

    Functional recovery after transplantation of brain-derived neurotrophic factor (BDNF)-modified neural stem cells (NSCs) was evaluated in a rat model of cerebral ischaemia damage induced by temporary middle cerebral artery occlusion (tMCAO). Western blotting and enzyme-linked immunosorbent assay demonstrated upregulated BDNF protein expression by rat embryonic NSCs transfected with the human BDNF gene (BDNF-NSCs). BDNF-NSCs stimulated neurite outgrowth in cocultured dorsal root ganglion neurons, suggesting that BDNF increased neurogenesis in vitro. In vivo, BDNF promoted recovery of tMCAO. Phosphate-buffered saline, untransformed NSCs or BDNF-NSCs were introduced into the penumbra zone of the right striatum of tMCAO rats and neurological function deficit was assessed for up to 12 weeks using the neurological severity score (NSS). The NSS was significantly lower in the BDNF-NSC transfected transplant group than in all the other groups from week 10. BDNF-NSCs recovered 1 week after transplantation expressed BDNF protein. Transplanted NSCs had differentiated into mature neurons 12 weeks after transplantation. Transgenic NSCs have potential as a therapeutic agent for brain ischaemia.

  6. Perforating eyelid injury extending to the brain stem in a 17-year-old woman: a case report

    Directory of Open Access Journals (Sweden)

    Yoshikawa-Kobayashi Izumi

    2010-01-01

    Full Text Available Abstract Introduction This case report describes a patient who had a perforating eyelid injury that extended to the brain stem. Case presentation A 17-year-old Japanese woman complained of decreased vision in her right eye, with severe ocular pain and headaches, after the metal tip of an umbrella struck her upper right eyelid accidentally. Her vision in the right eye decreased to light perception with commotio retinae, intraretinal hemorrhage, and severe lid swelling. Magnetic resonance imaging (MRI demonstrated edema of the head of the caudate nucleus and putamen, and the edema extended to the hypothalamus. The MRI findings indicated that the umbrella tip had penetrated through the eyelid and the posterior orbital wall. Vision improved to 20/50 in the right eye, with subretinal fibrosis caused by the choroidal rupture. Conclusions We recommend that MRI be performed on the orbit and brain in patients who appear to have symptoms that are inconsistent with the observed injury and when a severe orbitocranial injury is suspected.

  7. 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...

  8. 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...

  9. Amelioration of penetrating ballistic-like brain injury induced cognitive deficits after neuronal differentiation of transplanted human neural stem cells.

    Science.gov (United States)

    Spurlock, Markus S; Ahmed, Aminul Islam; Rivera, Karla N; Yokobori, Shoji; Lee, Stephanie W; Sam, Pingdewinde N; Shear, Deborah A; Hefferan, Michael P; Hazel, Thomas G; Johe, Karl K; Gajavelli, Shyam; Tortella, Frank C; Bullock, Ross

    2017-03-01

    Penetrating traumatic brain injury (PTBI) is one of the major cause of death and disability worldwide. Previous studies in penetrating ballistic-like brain injury (PBBI), a PTBI rat model revealed widespread peri-lesional neurodegeneration, similar to that seen in humans following gunshot wound to head, which is unmitigated by any available therapies to date. Therefore, we evaluated human neural stem cell (hNSC) engraftment to putatively exploit the potential of cell therapy that has been seen in other central nervous system injury models. Towards this, green fluorescent protein (GFP) labeled hNSCs (400,000 per animal) were transplanted in immunosuppressed Sprague Dawley (SD), Fisher, and athymic (ATN) PBBI rats one week after injury. Tacrolimus (3mg/kg two days prior to transplantation, then 1mg/kg/day), Methylprednisolone (10mg/kg on day of transplant, 1mg/kg/week thereafter), and Mycophenolate mofetil (30mg/kg/day) for seven days following transplantation were used to confer immunosuppression. Engraftment in SD and ATN was comparable at 8-weeks post transplantation. Evaluation of hNSC differentiation and distribution revealed increased neuronal differentiation of transplanted cells with time. At 16-weeks post-transplantation neither cell proliferation nor glial lineage markers expression was detected. Transplanted cell morphology was similar to neighboring host neurons and there was relatively little migration of cells from the peri-transplant site. By 16 weeks, GFP positive processes extended both rostro-caudally and bilaterally into parenchyma, spreading along host white matter tracts, traversing internal capsule, extending ~13 mm caudally from transplantation site reaching into the brain stem. In a Morris water maze test at 8-weeks post-transplantation, animals with transplants had shorter latency to platform compared to vehicle treated animals. However, weak injury-induced cognitive deficits in the control group at the delayed time point confounded benefits

  10. Influence of hyperbaric oxygen on the differentiation of hypoxic/ischemic brain-derived neural stem cells

    Institute of Scientific and Technical Information of China (English)

    Zhengrong Peng; Sue Wang; Pingtian Xiao

    2009-01-01

    BACKGROUND: It has been previously shown that hyperbaric oxygen may promote proliferation of neural stem cells and reduce death of endogenous neural stem cells (NSCs).OBJECTIVE: To explore the effects of hyperbaric oxygen on the differentiation of hypoxic/ischemic brain-derived NSCs into neuron-like cells and compare with high-concentration oxygen and high pressure.DESIGN, TIME AND SETTING: An in vitro contrast study, performed at Laboratory of Neurology,Central South University between January and May 2006.MATERIALS: A hyperbaric oxygen chamber (YLC 0.5/1A) was provided by Wuhan Shipping Design Research Institute; mouse anti-rat microtubute-associated protein 2 monoclonal antibody by Jingmei Company, Beijing; mouse anti-rat glial fibrillary acidic protein monoclonal antibody by Neo Markers,USA; mouse anti-rat galactocerebroside monoclonal antibody by Santa Cruz Biotechnology Inc.,USA; and goat anti-mouse fluorescein isothiocyanate-labeled secondary antibody by Wuhan Boster Bioengineering Co., Ltd., China.METHODS: Brain-derived NSCs isolated from brain tissues of neonatal Sprague Dawiey rats werecloned and passaged, and assigned into five groups: normal control, model, high-concentration oxygen, high pressure, and hyperbaric oxygen groups. Cells in the four groups, excluding the normal control group, were incubated in serum-containing DMEM/F12 culture medium. Hypoxic/ischemic models of NSCs were established in an incubator comprising 93% N2, 5% CO2, and 2% O2.Thereafter, cells were continuously cultured as follows: compressed air (0.2 MPa, 1 hour, once a day)in the high pressure group, compressed air+a minimum of 80% O2 in the hyperbaric oxygen group,and a minimum of 80% O2 in the high-concentration oxygen group. Cells in the normal control and model groups were cultured as normal.MAIN OUTCOME MEASURES: At day 7 after culture, glial fibrillary acidic protein,microtubule-associated protein 2, and galactocerebroside immunofluorescence staining were examined to

  11. Hyperbaric oxygen treatment promotes neural stem cell proliferation in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage.

    Science.gov (United States)

    Feng, Zhichun; Liu, Jing; Ju, Rong

    2013-05-05

    Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats (7 days old) subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2'-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2'-deoxyuridine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.

  12. Hyperbaric oxygen treatment promotes neural stem cell proliferation in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Zhichun Feng; Jing Liu; Rong Ju

    2013-01-01

    Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats (7 days old) subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2′-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2′- deoxyuridine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.

  13. A novel hypothesis of blood-brain barrier (BBB development and in vitro BBB model: neural stem cell is the driver of BBB formation and maintenance

    Directory of Open Access Journals (Sweden)

    Jian Lu

    2012-02-01

    Full Text Available There is an ongoing effort to develop in vitro models for the blood-brain barrier (BBB research and the central nervous system (CNS drug screening. But the phenotypes of the existing in vitro models are still very remote from those found in vivo. The trouble in establishing in vitro BBB models comes from the unclear mechanism of the BBB formation and maintenance. The astrocytes have been found to be responsible for the maintenance of the BBB, but the studies of the CNS development have shown that the BBB formation starts largely before the gliogenesis. We hypothesize here that the neural stem cell is the real driver of the BBB formation, development and maintenance. The formation of the BBB is initiated by the neural stem cells during the earliest stage of CNS angiogenesis. The maintenance of the BBB is driven by the soluble signals produced by the neural stem cells which exist in the dentate gyrus of the hippocampus and the subventricular zone throughout the life. The brain microvascular endothelial cells (BMEC-pericyte complex is the anatomical basis of the BBB. Based on our hypothesis we suggest using the neural stem cells to induce the BMEC-pericyte complex to establish in vitro BBB models. The further research on the role of the neural stem cells in the BBB formation and maintenance may elucidate the mechanism of the BBB development. [J Exp Integr Med 2012; 2(1.000: 39-43

  14. Regulation of endogenous neural stem/progenitor cells for neural repair - factors that promote neurogenesis and gliogenesis in the normal and damaged brain

    Directory of Open Access Journals (Sweden)

    Kimberly eChristie

    2013-01-01

    Full Text Available Neural stem/precursor cells in the adult brain reside in the subventricular zone (SVZ of the lateral ventricles and the subgranular zone (SGZ of the dentate gyrus in the hippocampus. These cells primarily generate neuroblasts that normally migrate to the olfactory bulb and the dentate granule cell layer respectively. Following brain damage, such as traumatic brain injury, ischemic stroke or in degenerative disease models, neural precursor cells from the SVZ in particular, can migrate from their normal route along the rostral migratory stream to the site of neural damage. This neural precursor cell response to neural damage is mediated by release of endogenous factors, including cytokines and chemokines produced by the inflammatory response at the injury site, and by the production of growth and neurotrophic factors. Endogenous hippocampal neurogenesis is frequently also directly or indirectly affected by neural damage. Administration of a variety of factors that regulate different aspects of neural stem/precursor biology often leads to improved functional motor and/or behavioural outcomes. Such factors can target neural stem/precursor proliferation, survival, migration and differentiation into appropriate neuronal or glial lineages. Newborn cells also need to subsequently survive and functionally integrate into extant neural circuitry, which may be the major bottleneck to the current therapeutic potential of neural stem/precursor cells. This review will cover the effects of a range of intrinsic and extrinsic factors that regulate neural stem /precursor cell functions. In particular it focuses on factors that may be harnessed to enhance the endogenous neural stem/precursor cell response to neural damage, highlighting those that have already shown evidence of preclinical effectiveness and discussing others that warrant further preclinical investigation.

  15. Microcephaly disease gene Wdr62 regulates mitotic progression of embryonic neural stem cells and brain size.

    Science.gov (United States)

    Chen, Jian-Fu; Zhang, Ying; Wilde, Jonathan; Hansen, Kirk C; Lai, Fan; Niswander, Lee

    2014-05-30

    Human genetic studies have established a link between a class of centrosome proteins and microcephaly. Current studies of microcephaly focus on defective centrosome/spindle orientation. Mutations in WDR62 are associated with microcephaly and other cortical abnormalities in humans. Here we create a mouse model of Wdr62 deficiency and find that the mice exhibit reduced brain size due to decreased neural progenitor cells (NPCs). Wdr62 depleted cells show spindle instability, spindle assembly checkpoint (SAC) activation, mitotic arrest and cell death. Mechanistically, Wdr62 associates and genetically interacts with Aurora A to regulate spindle formation, mitotic progression and brain size. Our results suggest that Wdr62 interacts with Aurora A to control mitotic progression, and loss of these interactions leads to mitotic delay and cell death of NPCs, which could be a potential cause of human microcephaly.

  16. Computerized three-dimensional reconstruction reveals cerebrovascular regulatory subregions in rat brain stem.

    Science.gov (United States)

    Underwood, M D; Arango, V; Smith, R W; Bakalian, M J; Mann, J J

    1993-09-01

    Three-dimensional wireframe reconstructions were used to examine the relationship between the anatomical localization of electrode sites and the cerebrovascular response which was elicited by electrical stimulation of the dorsal raphe nucleus (DRN). Reconstructions of the rat brain and DRN were done from atlas plates and from Nissl-stained coronal sections (100-micron increments). Data points were entered and three-dimensional reconstructions were performed using commercially available software and a personal computer. Display of the entire brain yielded views which obscured visualization of the DRN. The data file was edited to reduce the number of contours without affecting the display resolution of the DRN. Selective display of the DRN and electronic rotation from the coronal to a sagittal view revealed a functional organization of the cerebral blood flow responses which was not apparent in two-dimensional coronal sections.

  17. Hydrocephalus and Pressure on Brain Stem Cause Death in Patients with Neurofibromatosis Type 2

    Directory of Open Access Journals (Sweden)

    M. Khazaei

    2014-07-01

    Full Text Available Introduction: Neurofibromatosis type 2 is an inherited autosomal dominant syndrome, charac-terized by multiple neoplasms of the central and peripheral nervous system associated with ocular abnormalities. The most common tumor associated with the disease is the vestibulo-cochlear and in later stages are meningioma and other brain tumors. Case Report: The patient was a 35 year old woman admitted to the Farshchian hospital in Hamadan due to unconciousness and respiratory distress She had sensorineural hearing loss and inability to see due to decrease visulal acuity. In addition, due to lower extremity paresis she has been unable to walk and wheelchair-dependent for many years. Brain CT scan and MRI showed multiple tumors in the posterior fossa causing obstructive hydrocephalus even-tually caused the patient's death . Conclusion: Brain tumors, especially in the posterior fossa can cause death in Neurofibroma-tosis type 2. Early surgery can be life saving. (Sci J Hamadan Univ Med Sci 2014; 21 (2:167-170

  18. Long-term survival of human neural stem cells in the ischemic rat brain upon transient immunosuppression.

    Directory of Open Access Journals (Sweden)

    Laura Rota Nodari

    Full Text Available Understanding the physiology of human neural stem cells (hNSCs in the context of cell therapy for neurodegenerative disorders is of paramount importance, yet large-scale studies are hampered by the slow-expansion rate of these cells. To overcome this issue, we previously established immortal, non-transformed, telencephalic-diencephalic hNSCs (IhNSCs from the fetal brain. Here, we investigated the fate of these IhNSC's immediate progeny (i.e. neural progenitors; IhNSC-Ps upon unilateral implantation into the corpus callosum or the hippocampal fissure of adult rat brain, 3 days after global ischemic injury. One month after grafting, approximately one fifth of the IhNSC-Ps had survived and migrated through the corpus callosum, into the cortex or throughout the dentate gyrus of the hippocampus. By the fourth month, they had reached the ipsilateral subventricular zone, CA1-3 hippocampal layers and the controlateral hemisphere. Notably, these results could be accomplished using transient immunosuppression, i.e administering cyclosporine for 15 days following the ischemic event. Furthermore, a concomitant reduction of reactive microglia (Iba1+ cells and of glial, GFAP+ cells was also observed in the ipsilateral hemisphere as compared to the controlateral one. IhNSC-Ps were not tumorigenic and, upon in vivo engraftment, underwent differentiation into GFAP+ astrocytes, and β-tubulinIII+ or MAP2+ neurons, which displayed GABAergic and GLUTAmatergic markers. Electron microscopy analysis pointed to the formation of mature synaptic contacts between host and donor-derived neurons, showing the full maturation of the IhNSC-P-derived neurons and their likely functional integration into the host tissue. Thus, IhNSC-Ps possess long-term survival and engraftment capacity upon transplantation into the globally injured ischemic brain, into which they can integrate and mature into neurons, even under mild, transient immunosuppressive conditions. Most notably

  19. Diagnostic criteria of the state of the distributed brain stem regulatory structures in cerebrovascular diseases

    Directory of Open Access Journals (Sweden)

    Pogorelov A.V.

    2014-11-01

    Full Text Available The clinical-neurophysiological study of 62 patients with history of subtentorial ischemic stroke was carried out in order to determine the criteria of dysfunction of morphologically distributed stem regulatory structures. It was revealed that these disorders are sustainable with the possibility of recourse and influence on the course of stroke. It was marked the influence of this disorders on the levels of consciousness, severity of state, recovery rate, asthenia level, sleep function. Manifestations of cerebral cardiac syndrome, impaired attention, orientation reaction, speed of sensomotoric acts are also marked. Patients with these disorders have low rates of recovery of functions. Neurophysiological criteria of these disorders are the lack of expressive reactions in electroencephalography, reduction of their overall level, instability of rhythm - generating structures and others.

  20. Comparative analysis of the frequency and distribution of stem and progenitor cells in the adult mouse brain.

    Science.gov (United States)

    Golmohammadi, Mohammad G; Blackmore, Daniel G; Large, Beatrice; Azari, Hassan; Esfandiary, Ebrahim; Paxinos, George; Franklin, Keith B J; Reynolds, Brent A; Rietze, Rodney L

    2008-04-01

    The neurosphere assay can detect and expand neural stem cells (NSCs) and progenitor cells, but it cannot discriminate between these two populations. Given two assays have purported to overcome this shortfall, we performed a comparative analysis of the distribution and frequency of NSCs and progenitor cells detected in 400 mum coronal segments along the ventricular neuraxis of the adult mouse brain using the neurosphere assay, the neural colony forming cell assay (N-CFCA), and label-retaining cell (LRC) approach. We observed a large variation in the number of progenitor/stem cells detected in serial sections along the neuraxis, with the number of neurosphere-forming cells detected in individual 400 mum sections varying from a minimum of eight to a maximum of 891 depending upon the rostral-caudal coordinate assayed. Moreover, the greatest variability occurred in the rostral portion of the lateral ventricles, thereby explaining the large variation in neurosphere frequency previously reported. Whereas the overall number of neurospheres (3730 +/- 276) or colonies (4275 +/- 124) we detected along the neuraxis did not differ significantly, LRC numbers were significantly reduced (1186 +/- 188, 7 month chase) in comparison to both total colonies and neurospheres. Moreover, approximately two orders of magnitude fewer NSC-derived colonies (50 +/- 10) were detected using the N-CFCA as compared to LRCs. Given only 5% of the LRCs are cycling (BrdU+/Ki-67+) or competent to divide (BrdU+/Mcm-2+), and proliferate upon transfer to culture, it is unclear whether this technique selectively detects endogenous NSCs. Overall, caution should be taken with the interpretation and employment of all these techniques.

  1. [Effect of sleep deprivation on visual evoked potentials and brain stem auditory evoked potentials in epileptics].

    Science.gov (United States)

    Urumova, L T; Kovalenko, G A; Tsunikov, A I; Sumskiĭ, L I

    1984-01-01

    The article reports on the first study of the evoked activity of the brain in epileptic patients (n = 20) following sleep deprivation. An analysis of the data obtained has revealed a tendency to the shortening of the peak latent intervals of visual evoked potentials in the range of 100-200 mu sec and the V component and the interpeak interval III-V of evoked auditory trunk potentials in patients with temporal epilepsy. The phenomenon may indicate the elimination of stabilizing control involving the specific conductive pathways and, possibly, an accelerated conduction of a specific sensor signal.

  2. M2 Phenotype Microglia-derived Cytokine Stimulates Proliferation and Neuronal Differentiation of Endogenous Stem Cells in Ischemic Brain

    Science.gov (United States)

    Choi, Ja Yong; Kim, Jong Youl; Kim, Jae Young; Park, Joohyun; Lee, Won Taek

    2017-01-01

    Microglia play a key role in the immune response and inflammatory reaction that occurs in response to ischemic stroke. Activated microglia promote neuronal damage or protection in injured brain tissue. Extracellular signals polarize the microglia towards the M1/M2 phenotype. The M1/M2 phenotype microglia released pro- and anti-inflammatory cytokines which induce the activation of neural stem/progenitor cells (NSPCs). In this study, we investigated how the cytokines released by microglia affect the activation of NSPCs. First, we treated BV2 cells with a lipopolysaccharide (LPS; 20 ng/ml) for M1 phenotype microglia and interleukin-4 (IL-4; 20 ng/ml) for M2 phenotype microglia in BV2 cells. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 1 h. In ex vivo, brain sections containing the subventricular zone (SVZ) were cultured in conditioned media of M1 and M2 phenotype-conditioned media for 3 d. We measured the expression of cytokines in the conditioned media by RT-PCR and ELISA. The M2 phenotype microglia-conditioned media led to the proliferation and neural differentiation of NSPCs in the ipsilateral SVZ after ischemic stroke. The RT-PCR and ELISA results showed that the expression of TGF-α mRNA was significantly higher in the M2 phenotype microglia-conditioned media. These data support that M2 phenotype microglia-derived TGF-α is one of the key factors to enhance proliferation and neural differntiation of NSPCs after ischemic stroke.

  3. Exophytic pilocytic astrocytoma of the brain stem in an adult with encasement of the caudal cranial nerve complex (IX-XII): presurgical anatomical neuroimaging using MRI

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    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.)

  4. A REPORT OF 25 CASES OF TUMORS OF BRAIN STEM%脑干占位性病变25例报告

    Institute of Scientific and Technical Information of China (English)

    刘哲; 赵勇刚; 陈红旗; 阎宏伟; 石学; 张群玲

    2001-01-01

    Objective To evaluate the methods of surgical treatment for tumors of brain stem and their curative effects. Methods: 25 cases of tumors of brain stem were analysed retrospectively. Results: There were 18 cases of astrocytomas, 2 cases of cavernous angioma, 1 cases of hemangioblastoma, 1 cases of dermoid cyst, 1 cases of syringopontia, 1 cases of inflammatory granuloma accompanied with hecrosis and 1 cases of AVM of brain stem in 25 cases. Four patients died after operation. Conclusion: Extrinsic tumors of brain stem could be resected totally or subtotally, resulting in good outcome.%目的探讨脑干占位性病变的外科手术治疗方法与疗效。方法回顾分析25例外科手术治疗脑干占位性病变病例。结果 25例病人中,星形细胞瘤18例,海绵状血管瘤2例,血管母细胞瘤1例,表皮囊肿1例,桥脑空洞症1例,炎性肉芽肿组织伴坏死1例,脑干AVM 1例。手术后死亡4例。结论外生型脑干肿瘤可做到全切除或次全切除,外科手术效果佳。

  5. Comparative transcriptome analysis in induced neural stem cells reveals defined neural cell identities in vitro and after transplantation into the adult rodent brain.

    Science.gov (United States)

    Hallmann, Anna-Lena; Araúzo-Bravo, Marcos J; Zerfass, Christina; Senner, Volker; Ehrlich, Marc; Psathaki, Olympia E; Han, Dong Wook; Tapia, Natalia; Zaehres, Holm; Schöler, Hans R; Kuhlmann, Tanja; Hargus, Gunnar

    2016-05-01

    Reprogramming technology enables the production of neural progenitor cells (NPCs) from somatic cells by direct transdifferentiation. However, little is known on how neural programs in these induced neural stem cells (iNSCs) differ from those of alternative stem cell populations in vitro and in vivo. Here, we performed transcriptome analyses on murine iNSCs in comparison to brain-derived neural stem cells (NSCs) and pluripotent stem cell-derived NPCs, which revealed distinct global, neural, metabolic and cell cycle-associated marks in these populations. iNSCs carried a hindbrain/posterior cell identity, which could be shifted towards caudal, partially to rostral but not towards ventral fates in vitro. iNSCs survived after transplantation into the rodent brain and exhibited in vivo-characteristics, neural and metabolic programs similar to transplanted NSCs. However, iNSCs vastly retained caudal identities demonstrating cell-autonomy of regional programs in vivo. These data could have significant implications for a variety of in vitro- and in vivo-applications using iNSCs.

  6. 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.

  7. Activated regulatory T cell regulates neural stem cell proliferation in the subventricular zone of normal and ischemic mouse brain through interleukin 10

    Directory of Open Access Journals (Sweden)

    Jixian eWang

    2015-09-01

    Full Text Available Recent studies have demonstrated that the depletion of Regulatory T cells (Tregs inhibits neural progenitor cell migration after brain ischemia. However, whether Tregs affect neural stem/progenitor cell proliferation is unclear. We explored the effect of Tregs on neurogenesis in the subventricular zone after ischemia. Tregs were isolated and activated in vitro. Adult male C57BL/6 mice underwent 60 minutes transient middle cerebral artery occlusion (tMCAO. Then Tregs (1x105 were injected into the left lateral ventricle of normal and ischemic mouse brain. Neurogenesis was determined by immunostaining. The mechanism was examined by inhibiting interleukin 10 (IL-10 and transforming growth factor (TGF- signaling. We found that the number of BrdU+ cells in the subventricular zone was significantly increased in the activated Tregs-treated mice. Double immunostaining showed that these BrdU+ cells expressed Mash1. Blocking IL-10 reduced the number of Mash1+/BrdU+ cells, but increased the amount of GFAP+/BrdU+ cells. Here we conclude that activated Tregs enhanced neural stem cell proliferation in the subventricular zone of normal and ischemic mice; blockage of IL-10 abolished Tregs-mediated neural stem cell proliferation in vivo and in vitro. Our results suggest that activated Tregs promoted neural stem cell proliferation via IL-10, which provides a new therapeutic approach for ischemic stroke.

  8. Human fetal brain-derived neural stem/progenitor cells grafted into the adult epileptic brain restrain seizures in rat models of temporal lobe epilepsy.

    Science.gov (United States)

    Lee, Haejin; Yun, Seokhwan; Kim, Il-Sun; Lee, Il-Shin; Shin, Jeong Eun; Park, Soo Chul; Kim, Won-Joo; Park, Kook In

    2014-01-01

    Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal

  9. 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.

  10. 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.

  11. 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.

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

    Institute of Scientific and Technical Information of China (English)

    Xue-man Lv; Yan Liu; Fei Wu; Yi Yuan; Min Luo

    2016-01-01

    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. Human neural stem cells genetically modified to overexpress brain-derived neurotrophic factor promote functional recovery and neuroprotection in a mouse stroke model.

    Science.gov (United States)

    Lee, Hong J; Lim, In J; Lee, Min C; Kim, Seung U

    2010-11-15

    Intracerebral hemorrhage (ICH) is a lethal stroke type; mortality approaches 50%, and current medical therapy against ICH shows only limited effectiveness, so an alternative approach is required, such as stem cell-based cell therapy. Previously we have shown that intravenously transplanted human neural stem cells (NSCs) selectively migrate to the brain and promote functional recovery in rat ICH model, and others have shown that intracerebral infusion of brain-derived neurotrophic factor (BDNF) results in improved structural and functional outcome from cerebral ischemia. We postulated that human NSCs overexpressing BDNF transplanted into cerebral cortex overlying ICH lesion could provide improved survival of grafted NSCs and increased angiogenesis and behavioral recovery in mouse ICH model. ICH was induced in adult mice by injection of bacterial collagenase into striatum. The HB1.F3.BDNF (F3.BDNF) human NSC line produces sixfold higher amounts of BDNFF over the parental F3 cell line in vitro, induces behavioral improvement, and produces a threefold increase in cell survival at 2 weeks and 8 weeks posttransplantation. Brain transplantation of human NSCs overexpressing BDNF provided differentiation and survival of grafted human NSCs and renewed angiogenesis of host brain and functional recovery of ICH animals. These results indicate that the F3.BDNF human NSCs should be of great value as a cellular source for experimental studies involving cellular therapy for human neurological disorders, including ICH.

  14. 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.)

  15. Bilateral cerebellar and brain stem infarction resulting from vertebral artery injury following cervical trauma without radiographic damage of the spinal column: a case report.

    Science.gov (United States)

    Mimata, Yoshikuni; Murakami, Hideki; Sato, Kotaro; Suzuki, Yoshiaki

    2014-01-01

    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.

  16. Conventional and cross-correlation brain-stem auditory evoked responses in the white leghorn chick: rate manipulations

    Science.gov (United States)

    Burkard, R.; Jones, S.; Jones, T.

    1994-01-01

    Rate-dependent changes in the chick brain-stem auditory evoked response (BAER) using conventional averaging and a cross-correlation technique were investigated. Five 15- to 19-day-old white leghorn chicks were anesthetized with Chloropent. In each chick, the left ear was acoustically stimulated. Electrical pulses of 0.1-ms duration were shaped, attenuated, and passed through a current driver to an Etymotic ER-2 which was sealed in the ear canal. Electrical activity from stainless-steel electrodes was amplified, filtered (300-3000 Hz) and digitized at 20 kHz. Click levels included 70 and 90 dB peSPL. In each animal, conventional BAERs were obtained at rates ranging from 5 to 90 Hz. BAERs were also obtained using a cross-correlation technique involving pseudorandom pulse sequences called maximum length sequences (MLSs). The minimum time between pulses, called the minimum pulse interval (MPI), ranged from 0.5 to 6 ms. Two BAERs were obtained for each condition. Dependent variables included the latency and amplitude of the cochlear microphonic (CM), wave 2 and wave 3. BAERs were observed in all chicks, for all level by rate combinations for both conventional and MLS BAERs. There was no effect of click level or rate on the latency of the CM. The latency of waves 2 and 3 increased with decreasing click level and increasing rate. CM amplitude decreased with decreasing click level, but was not influenced by click rate for the 70 dB peSPL condition. For the 90 dB peSPL click, CM amplitude was uninfluenced by click rate for conventional averaging. For MLS BAERs, CM amplitude was similar to conventional averaging for longer MPIs.(ABSTRACT TRUNCATED AT 250 WORDS).

  17. Brain tumor stem cells maintain overall phenotype and tumorigenicity after in vitro culturing in serum-free conditions

    Science.gov (United States)

    Vik-Mo, Einar Osland; Sandberg, Cecilie; Olstorn, Havard; Varghese, Mercy; Brandal, Petter; Ramm-Pettersen, Jon; Murrell, Wayne; Langmoen, Iver Arne

    2010-01-01

    Traditional in vitro culturing of tumor cells has been shown to induce changes so that cultures no longer represent the tumor of origin. Serum-free culturing conditions are used in a variety of cancers to propagate stem-like cells in vitro. Limited reports, however, exist on the effects of such propagation. We have compared cells from brain tumor biopsies cultivated under serum-free conditions at passages 2 and 10 to describe the effects of in vitro culturing. We were able to establish cell lines from 7 of 10 biopsies from patients with glioblastoma. The cell lines adapted to conditions and had 2.2 times increased population doubling rate at later passages. Karyotyping and comparative genomic hybridization analysis revealed that all examined cell lines had cytogenetic aberrations commonly found in glioblastomas, and there were only minor differences between tumor and early and late passages in the same culture. Whole-transcriptome analysis shows that tumors had interindividual differences. Changes in the overall expression patterns through passaging were modest, with a significant change in only 14 genes; the variation among cultures was, however, reduced through passages. The ability to differentiate differed among tumors but was maintained throughout passaging. The cells initiated tumors upon transplantation to immunodeficient mice with differing phenotypes, but a given cell culture maintained tumor phenotype after serial cultivation. The cultures established maintained individual characteristics specific to culture identity. Thus, each cell culture reflects an image of the tumor—or a personalized model—from which it was derived and remains representative after moderate expansion. PMID:20843775

  18. Effects of brain-stem and thalamic lesions on the corneal reflex: an electrophysiological and anatomical study.

    Science.gov (United States)

    Ongerboer de Visser, B W; Moffie, D

    1979-09-01

    In 9 patients with Wallenberg's lateral medullary syndrome, one patient with a midbrain lesion involving the right side of the tegmentum, and 2 patients with a thalamic lesion, corneal reflexes were investigated by a new electromyographic technique. The electrophysical results were compared with the results obtained by clinical observation. In the lateral medullary lesions the electrophysiologically obtained reflex responses showed four types of abnormality. Type A consisted of a bilateral delay and type B a bilateral absence of the corneal reflex response to stimulation on the affected side in combination with a normal reflex response on both sides when the cornea on the normal side was stimulated. Type C, which was present in one case, and type D which was seen in 3 cases, consisted of a bilateral absence of the corneal reflex upon stimulation on the affected side; stimulation on the unaffected side produced a normal reflex response on the intact side in combination with, respectively, a delay or absence of the corneal reflex response on the affected side. Comparison of the clinical observations with the electrophysiological findings revealed minor discrepancies in type A and B abnormalities. However, the electrophysiological type C and D abnormalities were not detected by clinical observation. These findings demonstrate that electrophysiological recording of the corneal reflex may reveal clinically undetectable abnormalities. From the electrophysiological findings it is concluded that the corneal reflex is conducted along medullary pathways running both ipsilaterally and contralaterally from the stimulated side before connecting, respectively, with the ipsilateral and contralateral facial nucleus. From the anatomical findings it is suggested that the ascending pathways from the spinal fifth nerve complex to the facial nuclei are located in the lateral reticular formation of the lower brain-stem. The normal corneal reflex responses in the presence of thalamic and

  19. A Novel Biopsy Method for Isolating Neural Stem Cells from the Subventricular Zone of the Adult Rat Brain for Autologous Transplantation in CNS Injuries.

    Science.gov (United States)

    Aligholi, Hadi; Hassanzadeh, Gholamreza; Gorji, Ali; Azari, Hassan

    2016-01-01

    Despite all attempts the problem of regeneration in damaged central nervous system (CNS) has remained challenging due to its cellular complexity and highly organized and sophisticated connections. In this regard, stem cell therapy might serve as a viable therapeutic approach aiming either to support the damaged tissue and hence to reduce the subsequent neurological dysfunctions and impairments or to replace the lost cells and re-establish damaged circuitries. Adult neural stem/progenitor cells (NS/PCs) are one of the outstanding cell sources that can be isolated from the subventricular zone (SVZ) of the lateral ventricles. These cells can differentiate into neurons, astrocytes, and oligodendrocytes. Implanting autologous NS/PCs will greatly benefit the patients by avoiding immune rejection after implantation, better survival, and integration with the host tissue. Developing safe and efficient methods in small animal models will provide us with the opportunity to optimize procedures required to achieve successful human autologous NS/PC transplantation in near future. In this chapter, a highly controlled and safe biopsy method for harvesting stem cell containing tissue from the SVZ of adult rat brain is introduced. Then, isolation and expansion of NS/PCs from harvested specimen as well as the techniques to verify proliferation and differentiation capacity of the resulting NS/PCs are discussed. Finally, a method for assessing the biopsy lesion volume in the brain is described. This safe biopsy method in rat provides a unique tool to study autologous NS/PC transplantation in different CNS injury models.

  20. 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.

  1. Activation of expression of brain-derived neurotrophic factor at the site of implantation of allogenic and xenogenic neural stem (progenitor) cells in rats with ischemic cortical stroke.

    Science.gov (United States)

    Chekhonin, V P; Lebedev, S V; Volkov, A I; Pavlov, K A; Ter-Arutyunyants, A A; Volgina, N E; Savchenko, E A; Grinenko, N F; Lazarenko, I P

    2011-02-01

    Ischemic stroke was modeled in the sensorimotor zone of the brain cortex in adult rats. Rat embryonic nervous tissue, neural stem cells from human olfactory epithelium, and rat fibroblasts (cell control) were implanted into the peri-infarction area of rats of different groups immediately after stroke modeling. Expression of BDNF mRNA was analyzed 7 days after surgery by real-time PCR. BDNF expression in cell preparation before their implantation was minimum. The expression of BDNF mRNA increased by 5-6 times in the areas of implantation of rat fibroblasts and human olfactory epithelium and by 23 times in the area of implantation of rat embryonic nervous tissue compared to periinfarction areas without cell implantation. These findings confirm the possibility of realization of the therapeutic effects of neural stem cells via expression of trophic factors.

  2. Neuron-specific enolase expression in a rat model of radiation-induced brain injury following vascular endothelial growth factor-modified neural stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    Songhua Xiao; Chaohui Duan; Qingyu Shen; Yigang Xing; Ying Peng; Enxiang Tao; Jun Liu

    2009-01-01

    BACKGROUND:Previous studies have shown that transplantation of vascular endothelial growth factor (VEGF)-modified neural stem cells (NSC) provides better outcomes,compared with neural stem cells,in the treatment of brain damage.OBJECTIVE:To compare the effects of VEGF-modified NSC transplantation and NSC transplantation on radiation-induced brain injury,and to determine neuron-specific enolase (NSE) expression in the brain.DESIGN,TIME,AND SETTING:The randomized,controlled study was performed at the Linbaixin Experimental Center,Second Affiliated Hospital,Sun Yat-sen University,China from November 2007 to October 2008.MATERIALS:VEGF-medified C17.2 NSCs were supplied by Harvard Medical School,USA.Streptavidin-biotin-peroxidase-complex kit (Boster,China) and 5,6-carboxyfluorescein diacetate succinimidyl ester (Fluka,USA) were used in this study.METHODS:A total of 84 Sprague Dawley rats were randomly assigned to a blank control group (n=20),model group (n=20),NSC group (n=20),and a VEGF-modified NSC group (n=24).Rat models of radiation-induced brain injury were established in the model,NSC,and VEGF-modified NSC groups.At 1 week following model induction,10 μL (5×10~4 cells/μL) VEGF-modified NSCs or NSCs were respectively infused into the striatum and cerebral cortex of rats from the VEGF-modified NSC and NSC groups.A total of 10 μL saline was injected into rats from the blank control and model groups.MAIN OUTCOME MEASURES:NSE expression in the brain was detected by immunohistochemistry following VEGF-modified NSC transplantation.RESULTS:NSE expression was significantly decreased in the brains of radiation-induced brain injury rats (P<0.05).The number of NSE-positive neurons significantly increased in the NSC and VEGF-modified NSC groups,compared with the model group (P<0.05).NSE expression significantly increased in the VEGF-modified NSC group,compared with the NSC group,at 6 weeks following transplantation (P<0.05).CONCLUSION:VEGF-modified NSC

  3. Inhibition of cyclophosphamide-induced oxidative stress in brain by dietary inclusion of red dye extracts from sorghum (Sorghum bicolor) stem.

    Science.gov (United States)

    Oboh, Ganiya; Akomolafe, Toyin L; Adetuyi, Abayomi O

    2010-10-01

    The stem of sorghum is used as color additives in cooking meals and taken as beverages when steeped or boiled in water as folklore for the management of anemia and some other diseases. This study sought to assess the antioxidant and neuroprotective potentials of red dye extract from sorghum stem on cyclophosphamide-induced oxidative stress in rat brain. Wistar strain albino rats were fed diet supplemented with the red dye (0.5% and 1.0% inclusion) for 14 days. There was no significant difference (P > .05) in average feed intake and weight gain of rats fed the basal diet and the red dye-supplemented diet. However, intraperitoneal administration of cyclophosphamide (75 mg/kg of body weight) 24 hours prior the termination of the experiment caused a significant (P brain malondialdehyde (MDA) content and serum activities of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in those rats fed diet without the dye supplement, whereas there was a significant decrease (P brain MDA content and serum enzyme activities in rats fed diet with the dye in a concentration-dependent manner. The protective effect of the red dye against cyclophosphamide-induced oxidative stress could be attributed to the high phenolic content (56.2%) and antioxidant activities of the red dye as typified by 2,2-diphenyl-1-picrylhydrazyl free radical scavenging ability, reducing properties, and Fe(2+) chelating ability. Therefore, dietary inclusion of the red dye from sorghum stem could be harnessed in the management of neurodegenerative diseases associated with oxidative stress.

  4. Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

    Science.gov (United States)

    2010-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:20663133

  5. Will brain cells derived from induced pluripotent stem cells or directly converted from somatic cells (iNs) be useful for schizophrenia research?

    Science.gov (United States)

    Filippich, Cheryl; Wolvetang, Ernst J; Mowry, Bryan J

    2013-09-01

    The reprogramming of nonneuronal somatic cells to induced pluripotent stem cells and their derivation to functional brain cells as well as the related methods for direct conversion of somatic cells to neurons have opened up the possibility of conducting research on cellular disease models from living schizophrenia patients. We review the published literature on schizophrenia that has used this rapidly developing technology, highlighting the need for specific aims and reproducibility. The key issues for consideration for future schizophrenia research in this field are discussed and potential investigations using this technology are put forward for critical assessment by the reader.

  6. 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 postnatal 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.

  7. Acupuncture at the San Jiao meridian affects brain stem issue G protein content in a rat migraine model

    Institute of Scientific and Technical Information of China (English)

    Sue Wang; Wei Li; Guangwei Zhong; Zhenyan Li; Lingbo Wen

    2008-01-01

    , stimulatory G protein concentration was significantly increased, while inhibitory G protein levels were significantly decreased in the model group (P 0.05). CONCLUSION: Dysfunctional G protein signal transductions in the rat brain stem may be responsible for migraine attack. Acupuncture at the San Jiao meridian ameliorates migraines by mediating the G protein signal transduction pathway.

  8. Brain-derived neurotrophic factor genes transfect rat bone marrow mesenchymal stem cells based on cationic polymer vector

    Institute of Scientific and Technical Information of China (English)

    Zunsheng Zhang; Kun Zan; Yonghai Liu; Xia Shen

    2009-01-01

    BACKGROUND: Gene therapy is an effective expression of genes within target cells after transferring exogenous target genes. Both vector selection and transfection method are important factors for gene transfection. An ideal gene vector is required for a high transfusion of target gene and an exact introduction of target gene into specific target cells so as to express gene products. OBJECTIVE: To study the expression of mRNA and protein after transfecting rat bone marrow mesenchymal stem cells (BMSCs) with brain-derived neurotrophic factor (BDNF) genes based on cationic polymer vector. DESIGN, TIME AND SETTING: A randomized, controlled in vitro study using gene engineering, performed at the Neurobiology Laboratory, Xuzhou Medical College between October 2007 and April 2008. MATERIALS: PcDNA3.1 BDNF was obtained from Youbiai Biotechnological Company, Beijing and cationic polymer vector used was the SofastTM gene transfection reagent that was made by Taiyangma Biotechnological Co., Ltd., Xiamen. METHODS: BMSCs extracted from six Sprague Dawley (SD) rats aged 1 month were isolated and cultured in vitro. Third passage BMSCs were inoculated on a 6-well culture plate at the density of 1×106 cells/L. At about 80% confluence, BMSCs were transfected with PcDNA3.1-BDNF (2 μg) combined with SofastTM gene transfection reagent (6 μg) (BDNF group) or with PcDNA3.1 (2 μg) combined with SofastTM gene transfection reagent (6 μg) (blank vector group). Cells that were not transfected with any reagents but still cultured under primary culture conditions were used as a non-transfection group.MAIN OUTCOME MEASURES: Enzyme linked immunosorbent assay was used to measure time efficiency of BMSC-secreted BDNF protein. Twenty-four hours after gene transfection, RT-PCR was used to detect expression of BDNF mRNA in the BMSCs. Immunohistochemistry was used to determine expression of BDNF protein in the BMSCs.RESULTS: BDNF protein expression was detected at day 1 after gene transfection

  9. 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

  10. PINK1 Deficiency Decreases Expression Levels of mir-326, mir-330, and mir-3099 during Brain Development and Neural Stem Cell Differentiation

    Science.gov (United States)

    Choi, Insup; Woo, Joo Hong; Jou, Ilo

    2016-01-01

    PTEN-induced putative kinase 1 (PINK1) is a Parkinson's disease (PD) gene. We examined miRNAs regulated by PINK1 during brain development and neural stem cell (NSC) differentiation, and found that lvels of miRNAs related to tumors and inflammation were different between 1-day-old-wild type (WT) and PINK1-knockout (KO) mouse brains. Notably, levels of miR-326, miR-330 and miR-3099, which are related to astroglioma, increased during brain development and NSC differentiation, and were significantly reduced in the absence of PINK1. Interestingly, in the presence of ciliary neurotrophic factor (CNTF), which pushes differentiation of NSCs into astrocytes, miR-326, miR-330, and miR-3099 levels in KO NSCs were also lower than those in WT NSCs. Furthermore, mimics of all three miRNAs increased expression of the astrocytic marker glial fibrillary acidic protein (GFAP) during differentiation of KO NSCs, but inhibitors of these miRNAs decreased GFAP expression in WT NSCs. Moreover, these miRNAs increased the translational efficacy of GFAP through the 3'-UTR of GFAP mRNA. Taken together, these results suggest that PINK1 deficiency reduce expression levels of miR-326, miR-330 and miR-3099, which may regulate GFAP expression during NSC differentiation and brain development. PMID:26924929

  11. A new method for piercing the tentorium cerebelli for implanting fragile electrodes into the brain stem in the rhesus monkey (Macaca mulatta).

    Science.gov (United States)

    Wu, Jing; Wang, Wenchao; Rizak, Joshua Dominic; Wang, Zhengbo; Wang, Jianhong; Feng, Xiaoli; Dong, Jinrun; Li, Lin; Liu, Li; Xu, Liqi; Yang, Shangchuan; Hu, Xintian

    2014-03-01

    Recent developments in neuron recording techniques include the invention of some fragile electrodes. The fragility of these electrodes impedes their successful use in deep brain recordings because it is difficult to penetrate the electrodes through the dura mater, especially the tentorium cerebelli (TC) enclosing the cerebellum and brain stem. This paper reports a new method to pierce the TC for inserting fragile electrodes into the inferior colliculus of rhesus monkeys. Briefly, a unique tool kit, consisting of needles with sharp tips, a guide tube and an "impactor," was used in a multistep protocol to pierce the TC. The impactor provided a brief force that quickly thrusts the needles through the meninges without causing significant damage to the brain tissue under the TC. Using this novel approach, tetrodes were successfully implanted into the inferior colliculus of a rhesus monkey and neuronal discharge signals were recorded. This method, which is simple, convenient and economical, allows neurophysiologists to study the electrophysiological characteristics of deep brain structures under the TC with advanced, albeit fragile, electrodes.

  12. Activated regulatory T cell regulates neural stem cell proliferation in the subventricular zone of normal and ischemic mouse brain through interleukin 10

    Science.gov (United States)

    Wang, Jixian; Xie, Luokun; Yang, Chenqi; Ren, Changhong; Zhou, Kaijing; Wang, Brian; Zhang, Zhijun; Wang, Yongting; Jin, Kunlin; Yang, Guo-Yuan

    2015-01-01

    Recent studies have demonstrated that the depletion of Regulatory T cells (Tregs) inhibits neural progenitor cell migration after brain ischemia. However, whether Tregs affect neural stem/progenitor cell proliferation is unclear. We explored the effect of Tregs on neurogenesis in the subventricular zone (SVZ) after ischemia. Tregs were isolated and activated in vitro. Adult male C57BL/6 mice underwent 60 min transient middle cerebral artery occlusion (tMCAO). Then Tregs (1 × 105) were injected into the left lateral ventricle (LV) of normal and ischemic mouse brain. Neurogenesis was determined by immunostaining. The mechanism was examined by inhibiting interleukin 10 (IL-10) and transforming growth factor (TGF-β) signaling. We found that the number of BrdU+ cells in the SVZ was significantly increased in the activated Tregs-treated mice. Double immunostaining showed that these BrdU+ cells expressed Mash1. Blocking IL-10 reduced the number of Mash1+/BrdU+ cells, but increased the amount of GFAP+/BrdU+ cells. Here, we conclude that activated Tregs enhanced neural stem cell (NSC) proliferation in the SVZ of normal and ischemic mice; blockage of IL-10 abolished Tregs-mediated NSC proliferation in vivo and in vitro. Our results suggest that activated Tregs promoted NSC proliferation via IL-10, which provides a new therapeutic approach for ischemic stroke. PMID:26441532

  13. The Anti-Tumor Effects of Adipose Tissue Mesenchymal Stem Cell Transduced with HSV-Tk Gene on U-87-Driven Brain Tumor.

    Directory of Open Access Journals (Sweden)

    Suely Maymone de Melo

    Full Text Available Glioblastoma (GBM is an infiltrative tumor that is difficult to eradicate. Treating GBM with mesenchymal stem cells (MSCs that have been modified with the HSV-Tk suicide gene has brought significant advances mainly because MSCs are chemoattracted to GBM and kill tumor cells via a bystander effect. To use this strategy, abundantly present adipose-tissue-derived mesenchymal stem cells (AT-MSCs were evaluated for the treatment of GBM in mice. AT-MSCs were prepared using a mechanical protocol to avoid contamination with animal protein and transduced with HSV-Tk via a lentiviral vector. The U-87 glioblastoma cells cultured with AT-MSC-HSV-Tk died in the presence of 25 or 50 μM ganciclovir (GCV. U-87 glioblastoma cells injected into the brains of nude mice generated tumors larger than 3.5 mm2 after 4 weeks, but the injection of AT-MSC-HSV-Tk cells one week after the U-87 injection, combined with GCV treatment, drastically reduced tumors to smaller than 0.5 mm2. Immunohistochemical analysis of the tumors showed the presence of AT-MSC-HSV-Tk cells only within the tumor and its vicinity, but not in other areas of the brain, showing chemoattraction between them. The abundance of AT-MSCs and the easier to obtain them mechanically are strong advantages when compared to using MSCs from other tissues.

  14. In vivo near-infrared imaging for the tracking of systemically delivered mesenchymal stem cells: tropism for brain tumors and biodistribution

    Directory of Open Access Journals (Sweden)

    Kim SM

    2015-12-01

    Full Text Available Seong Muk Kim,1 Chang Hyun Jeong,2 Ji Sun Woo,2 Chung Heon Ryu,1 Jeong-Hwa Lee,3 Sin-Soo Jeun1,21Postech-Catholic Biomedical Engineering Institute, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 2Department of Neurosurgery, Seoul St Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea; 3Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul, KoreaAbstract: Mesenchymal stem cell (MSC-based gene therapy is a promising tool for the treatment of various neurological diseases, including brain tumors. However, the tracking of in vivo stem cell migration, distribution, and survival need to be defined for their clinical application. The systemic routes of stem cell delivery must be determined because direct intracerebral injection as a cure for brain tumors is an invasive method. In this study, we show for the first time that near-infrared (NIR imaging can reveal the distribution and tumor tropism of intravenously injected MSCs in an intracranial xenograft glioma model. MSCs were labeled with NIR fluorescent nanoparticles, and the effects of the NIR dye on cell proliferation and migratory capacity were evaluated in vitro. We investigated the tumor-targeting properties and tissue distribution of labeled MSCs introduced by intravenous injection and followed by in vivo imaging analysis, histological analysis, and real-time quantitative polymerase chain reaction. We observed no cytotoxicity or change in the overall growth rate and characteristics of labeled MSCs compared with control MSCs. NIR fluorescent imaging showed the organ distribution and targeted tumor tropism of systemically injected human MSCs. A significant number of MSCs accumulated specifically at the tumor site in the mouse brain. These results suggest that NIR-based cell tracking is a potentially useful imaging technique to visualize cell survival, migration, and distribution for the application of MSC

  15. Transplantation of bone marrow mesenchymal stem cells decreases oxidative stress, apoptosis, and hippocampal damage in brain of a spontaneous stroke model.

    Science.gov (United States)

    Calió, Michele Longoni; Marinho, Darci Sousa; Ko, Gui Mi; Ribeiro, Renata Rodrigues; Carbonel, Adriana Ferraz; Oyama, Lila Missae; Ormanji, Milene; Guirao, Tatiana Pinoti; Calió, Pedro Luiz; Reis, Luciana Aparecida; Simões, Manuel de Jesus; Lisbôa-Nascimento, Telma; Ferreira, Alice Teixeira; Bertoncini, Clélia Rejane Antônio

    2014-05-01

    Stroke is the most common cause of motor disabilities and is a major cause of mortality worldwide. Adult stem cells have been shown to be effective against neuronal degeneration through mechanisms that include both the recovery of neurotransmitter activity and a decrease in apoptosis and oxidative stress. We chose the lineage stroke-prone spontaneously hypertensive rat (SHRSP) as a model for stem cell therapy. SHRSP rats can develop such severe hypertension that they generally suffer a stroke at approximately 1 year of age. The aim of this study was to evaluate whether mesenchymal stem cells (MSCs) decrease apoptotic death and oxidative stress in existing SHRSP brain tissue. The results of qRT-PCR assays showed higher levels of the antiapoptotic Bcl-2 gene in the MSC-treated animals, compared with untreated. Our study also showed that superoxide, apoptotic cells, and by-products of lipid peroxidation decreased in MSC-treated SHRSP to levels similar those found in the animal controls, Wistar Kyoto rats. In addition, we saw a repair of morphological damage at the hippocampal region after MSC transplantation. These data suggest that MSCs have neuroprotective and antioxidant potential in stroke-prone spontaneously hypertensive rats.

  16. Effects of lateral ventricular transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene on cognition in a rat model of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Ping Zhang; Gangyong Zhao; Xianjiang Kang; Likai Su

    2012-01-01

    In the present study, transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene into the lateral ventricle of a rat model of Alzheimer's disease, resulted in significant attenuation of nerve cell damage in the hippocampal CA1 region. Furthermore, brain-derived neurotrophic factor and tyrosine kinase B mRNA and protein levels were significantly increased, and learning and memory were significantly improved. Results indicate that transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene can significantly improve cognitive function in a rat model of Alzheimer's disease, possibly by increasing the levels of brain-derived neurotrophic factor and tyrosine kinase B in the hippocampus.

  17. 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

  18. Adipose-derived mesenchymal stem cell transplantation promotes adult neurogenesis in the brains of Alzheimer’s disease mice

    Institute of Scientific and Technical Information of China (English)

    Yufang Yan; Tuo Ma; Kai Gong; Qiang Ao; Xiufang Zhang; Yandao Gong

    2014-01-01

    In the present study, we transplanted adipose-derived mesenchymal stem cells into the hippo-campi of APP/PS1 transgenic Alzheimer’s disease model mice. Immunofluorescence staining revealed that the number of newly generated (BrdU+) cells in the subgranular zone of the dentate gyrus in the hippocampus was signiifcantly higher in Alzheimer’s disease mice after adipose-de-rived mesenchymal stem cell transplantation, and there was also a significant increase in the number of BrdU+/DCX+neuroblasts in these animals. Adipose-derived mesenchymal stem cell transplantation enhanced neurogenic activity in the subventricular zone as well. Furthermore, adipose-derived mesenchymal stem cell transplantation reduced oxidative stress and alleviated cognitive impairment in the mice. Based on these ifndings, we propose that adipose-derived mes-enchymal stem cell transplantation enhances endogenous neurogenesis in both the subgranular and subventricular zones in APP/PS1 transgenic Alzheimer’s disease mice, thereby facilitating functional recovery.

  19. Protective effect of bone marrow-derived mesenchymal stem cells on dopaminergic neurons against 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in rat brain slices

    Institute of Scientific and Technical Information of China (English)

    Lirong Jin; Zhen Hong; Chunjiu Zhong; Yang Wang

    2009-01-01

    BACKGROUND: To date, the use of bone marrow-derived mesenchymal stem cells (MSCs) for the treatment of Parkinson's disease have solely focused on in vivo animal models. Because of the number of influencing factors, it has been difficult to determine a consistent outcome. OBJECTIVE: To establish an injury model in brain slices of substantia nigra and striatum using 1-methyl-4-phenylpytidinium ion (MPP+), and to investigate the effect of MSCs on dopaminergic neurons following MPP+ induced damage.DESIGN, TIME AND SETTING: An in vitro, randomized, controlled, animal experiment using immunohistochemistry was performed at the Laboratory of the Department of Anatomy, Fudan University between January 2004 and December 2006.MATERIALS: Primary MSC cultures were obtained from femurs and tibias of adult Sprague Dawley rats. Organotypic brain slices were isolated from substantia nigra and striatum of 1-day-old Sprague Dawley rat pups. Monoclonal antibodies for tyrosine hydroxylase (TH, 1:5 000) were from Santa Cruz (USA); goat anti-rabbit IgG antibodies labeled with FITC were from Boster Company (China).METHODS: Organotypic brain slices were cultured for 5 days in whole culture medium supplemented with 50% DMEM, 25% equine serum, and 25% Tyrode's balanced salt solution. The medium was supplemented with 5 μg/mL Ara-C, and the culture was continued for an additional 5 days. The undergrowth of brain slices was discarded at day 10. Eugonic brain slices were cultured with basal media for an additional 7 days. The brain slices were divided into three groups: control, MPP+ exposure, and co-culture. For the MPP+ group, MPP+ (30 μmol/L) was added to the media at day 17 and brain slices were cultured for 4 days, followed by control media. For the co-culture group, the MPP+ injured brain slices were placed over MSCs in the well and were further cultured for 7 days.MAIN OUTCOME MEASURES: After 28 days in culture, neurite outgrowth was examined in the brain slices under phase

  20. 脑损伤修复与成体干细胞的可塑性%Plasticity of adult stem cells in the rehabilitation of brain injury

    Institute of Scientific and Technical Information of China (English)

    何念海; 赵文利; 王宇明

    2005-01-01

    目的:成体干细胞体在内外可分化为神经细胞而用于脑损伤修复,探讨成体干细胞用于脑损伤康复的可行性可为脑功能恢复的临床实践提供前瞻性依据.资料来源:应用计算机检索Medline 1998-01/2004-04和PubMed1998-01/2004-04期间的相关文章,检索词"stem cell,cerebral injury,rehabilitation",并限定文章语言种类为English.同时计算机检索杂志1997-01/2004-04期间的相关文章,限定文章语言种类为中文,检索词"干细胞、脑损伤、康复".资料选择:对资料进行初审,选取包括成体干细胞分化为神经细胞及其用于脑损伤治疗的实验和l临床研究文献,查找文献全文.资料提炼:共收集到33篇关于成体干细胞可塑性分化及其用于脑损伤的研究文献.资料综合:33篇文献证明了成体干细胞可分化为神经细胞及其可能的机制,并证明了成体干细胞移植治疗脑损伤的有效性.结论:已有研究充分证明成体干细胞在体内外可分化为神经细胞,并可用于脑损伤的修复.%OBJECTIVE: Adult stem cells(ASCs) have been applied to the rehabilitation of brain injury for its capability of differentiation into neural cells both in vitro and in vivo, thereby to explore the feasibility of application of ASCs to the rehabilitation of brain injury could provide prospective basis for clinical practice in brain functional recovery.DATA SOURCES: Relative articles were computer-searched in Medline and PubMed between January 1998 and April 2004 , with the key word of"stem cell, cerebral injury, rehabilitation" and language limited to English. Meanwhile similar articles in Chinese Journal of Clinical Rehabilitation from January 1997 to April 2004 were also searched with the same key words in Chinese.STUDY SELECTION: Literatures concerning the differentiation of ASCs into neural cells, as well as experimental and clinical studies on their application in brain injuries were adopted after first trial

  1. Effects of Choto-san and hooks and stems of Uncaria sinensis on antioxidant enzyme activities in the gerbil brain after transient forebrain ischemia.

    Science.gov (United States)

    Yokoyama, Koichi; Shimada, Yutaka; Hori, Etsuro; Nakagawa, Takako; Takagi, Shinobu; Sekiya, Nobuyasu; Kouta, Kazufumi; Nishijo, Hisao; Yokozawa, Takako; Terasawa, Katsutoshi

    2004-12-01

    Previously, we revealed that oral administrations of Choto-san, a Kampo formula, and the hooks and stems of Uncaria sinensis Haviland (Rubiaceae), a medicinal plant comprising Choto-san, enhanced superoxide anion and hydroxyl radical scavenging activities in the hippocampus, and prevented delayed neuronal death of pyramidal cells in the hippocampal CA1 region in a transient forebrain ischemia gerbil model. In the present study, for the purpose of clarifying whether the endogenous antioxidant enzymes contribute to these mechanisms, we investigated the effects of Choto-san extract (CSE) and Uncaria sinensis extract (USE) on superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities in the brain by using the same experimental model. 1.0% CSE or 3.0% USE were dissolved in water and provided to gerbils ad libitum from 7 days prior to ischemia/reperfusion (i/rp). Seven days of continuous administrations of CSE or USE without i/rp procedure enhanced CAT activity but not SOD and GSH-Px activities in both the hippocampus and cortex. CSE elevated CAT activity in the hippocampus at 7 days and in the cortex at 3h after i/rp. USE raised CAT activity in both the hippocampus and cortex at 3 h and 7 days after i/rp. These results suggest that one of the mechanisms of the protective effects of CSE and USE against transient brain ischemia-induced neuronal damage may be their enhancing effect on CAT activity in the brain.

  2. 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.

  3. Bombesin receptors and transplanted stem cells in rat brain: High-resolution scan with 99mTc BN1.1

    Science.gov (United States)

    Scopinaro, F.; Paschali, E.; Di Santo, G.; Antonellis, T.; Massari, R.; Trotta, C.; Gourni, H.; Bouziotis, P.; David, V.; Soluri, A.; Varvarigou, A. D.

    2006-12-01

    The aim of this work is to detect the presence of transplanted stem cells (TSC) in rat brain with high-resolution (HR) scintigraphy and labelled bombesin (BN). BN is a morphogen for Central Nervous System (CNS) as well as for other organs: CNS-oriented TSC over-express BN Receptors (BNR). BN is also a neurotransmitter and modulates several functions of CNS. 99mTc labelled BN-like peptide scan of CNS is the ideal method to detect growing TSC once knowing normal distribution of BNRs in CNS. HR Planar and single photon emission computerized tomography (SPECT) images of rat brain were performed with new HR detectors (Li-tech, Italy). Pertechnetate, 99mTc HMPAO and the new 99mTc BN1.1 (patented) were i.v. administered in five rats. HR SPECT of 99mTc BN1.1 detected olfactory tract, fronto-lateral cortex, cerebellum, basal ganglia and amygdale. Results of SPECT were confirmed by bio-distribution study performed after autopsy of three of the five rats. The remaining two rats underwent cerebral lesions followed by transplant of TSC. Three months later, HR scintigraphy was repeated and showed images completely different from previous basal study, with hot spot of 99mTc BN1.1 corresponding to the site of TSC transplant. Immuno-histochemistry confirmed the presence of viable TSC. Not only 99mTc BN1.1 HR scan showed viability of transplanted TSC but also the "background brain" was the still now unknown map of BNR in mammalian brain.

  4. 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).

  5. Intranasal delivery of bone marrow-derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimer's and Parkinson's disease.

    Science.gov (United States)

    Danielyan, Lusine; Beer-Hammer, Sandra; Stolzing, Alexandra; Schäfer, Richard; Siegel, Georg; Fabian, Claire; Kahle, Philipp; Biedermann, Tilo; Lourhmati, Ali; Buadze, Marine; Novakovic, Ana; Proksch, Barbara; Gleiter, Christoph H; Frey, William H; Schwab, Matthias

    2014-01-01

    In view of the rapid preclinical development of cell-based therapies for neurodegenerative disorders, traumatic brain injury, and tumors, the safe and efficient delivery and targeting of therapeutic cells to the central nervous system is critical for maintaining therapeutic efficacy and safety in the respective disease models. Our previous data demonstrated therapeutically efficacious and targeted delivery of mesenchymal stem cells (MSCs) to the brain in the rat 6-hydroxydopamine model of Parkinson's disease (PD). The present study examined delivery of bone marrow-derived MSCs, macrophages, and microglia to the brain in a transgenic model of PD [(Thy1)-h[A30P] αS] and an APP/PS1 model of Alzheimer's disease (AD) via intranasal application (INA). INA of microglia in naive BL/6 mice led to targeted and effective delivery of cells to the brain. Quantitative PCR analysis of eGFP DNA showed that the brain contained the highest amount of eGFP-microglia (up to 2.1 × 10(4)) after INA of 1 × 10(6) cells, while the total amount of cells detected in peripheral organs did not exceed 3.4 × 10(3). Seven days after INA, MSCs expressing eGFP were detected in the olfactory bulb (OB), cortex, amygdala, striatum, hippocampus, cerebellum, and brainstem of (Thy1)-h[A30P] αS transgenic mice, showing predominant distribution within the OB and brainstem. INA of eGFP-expressing macrophages in 13-month-old APP/PS1 mice led to delivery of cells to the OB, hippocampus, cortex, and cerebellum. Both MSCs and macrophages contained Iba-1-positive population of small microglia-like cells and Iba-1-negative large rounded cells showing either intracellular amyloid β (macrophages in APP/PS1 model) or α-synuclein [MSCs in (Thy1)-h[A30P] αS model] immunoreactivity. Here, we show, for the first time, intranasal delivery of cells to the brain of transgenic PD and AD mouse models. Additional work is needed to determine the optimal dosage (single treatment regimen or repeated

  6. Analysis of brain-stem auditory evoked potential and visual evoked potential in patients with Parkinson disease

    Institute of Scientific and Technical Information of China (English)

    Qiaorong Deng; Jianzhong Deng; Yanmin Zhao; Xiaohai Yan; Pin Chen

    2006-01-01

    BACKGROUND: With the development of neuroelectrophysiology, it had been identified that all kinds of evoked potentials might reflect the functional status of corresponding pathway. Evoked potentials recruited in the re search of PD, it can be known whether other functional pathway of nervous system is impaired. OBJECTIVE: To observe whether brainstem auditory and visual passageway are impaired in patients with Parkinson disease (PD), and compare with non-PD patients concurrently. DESIGN: A non-randomized concurrent controlled observation. SETTINGS: Henan Provincial Tumor Hospital; Anyang District Hospital. PARTICIPANTS: Thirty-two cases of PD outpatients and inpatients, who registered in the Department of Neurology, Anyang District Hospital from October 1997 to February 2006, were enrolled as the PD group, including 20 males and 12 females, aged 50-72 years old. Inclusive criteria: In accordance with the diagnostic criteria of PD recommended by the dyskinesia and PD group of neurology branch of Chinese Medical Association. Patients with diseases that could cause Parkinson syndrome were excluded by CT scanning or MRI examination. Meanwhile, 30 cases with non-neurological disease were selected from the Department of Internal Medicine of our hospital as the control group, including 19 males and 11 females, aged 45-70 years old. Including criteria: Without history of neurological disease or psychiatric disease; showing normal image on CT. And PD, Parkinson syndrome and Parkinsonism-plus were excluded by professional neurologist. All the patients were informed and agreed with the examination and clinical observation. METHODS: The electrophysiological examination and clinical observation of the PD patients and controls were conducted. The Reporter type 4-channel evoked potential machine (Italy) was used to check brain-stem auditory evoked potential (BAEP) and visual evoked potential (VEP). Why to be examined was explained to test taker. BAEP recording electrode was plac

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

    Science.gov (United States)

    Chung, Chiu-Yen; Lin, Martin Hsiu-Chu; Lee, I-Neng; Lee, Tsong-Hai; Lee, Ming-Hsueh; Yang, Jen-Tsung

    2017-01-01

    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. PMID:28335495

  8. Glioma Stem Cells but Not Bulk Glioma Cells Upregulate IL-6 Secretion in Microglia/Brain Macrophages via Toll-like Receptor 4 Signaling.

    Science.gov (United States)

    a Dzaye, Omar Dildar; Hu, Feng; Derkow, Katja; Haage, Verena; Euskirchen, Philipp; Harms, Christoph; Lehnardt, Seija; Synowitz, Michael; Wolf, Susanne A; Kettenmann, Helmut

    2016-05-01

    Peripheral macrophages and resident microglia constitute the dominant glioma-infiltrating cells. The tumor induces an immunosuppressive and tumor-supportive phenotype in these glioma-associated microglia/brain macrophages (GAMs). A subpopulation of glioma cells acts as glioma stem cells (GSCs). We explored the interaction between GSCs and GAMs. Using CD133 as a marker of stemness, we enriched for or deprived the mouse glioma cell line GL261 of GSCs by fluorescence-activated cell sorting (FACS). Over the same period of time, 100 CD133(+ )GSCs had the capacity to form a tumor of comparable size to the ones formed by 10,000 CD133(-) GL261 cells. In IL-6(-/-) mice, only tumors formed by CD133(+ )cells were smaller compared with wild type. After stimulation of primary cultured microglia with medium from CD133-enriched GL261 glioma cells, we observed an selective upregulation in microglial IL-6 secretion dependent on Toll-like receptor (TLR) 4. Our results show that GSCs, but not the bulk glioma cells, initiate microglial IL-6 secretion via TLR4 signaling and that IL-6 regulates glioma growth by supporting GSCs. Using human glioma tissue, we could confirm the finding that GAMs are the major source of IL-6 in the tumor context.

  9. Synergy of endothelial and neural progenitor cells from adipose-derived stem cells to preserve neurovascular structures in rat hypoxic-ischemic brain injury.

    Science.gov (United States)

    Hsueh, Yuan-Yu; Chang, Ya-Ju; Huang, Chia-Wei; Handayani, Fitri; Chiang, Yi-Lun; Fan, Shih-Chen; Ho, Chien-Jung; Kuo, Yu-Min; Yang, Shang-Hsun; Chen, Yuh-Ling; Lin, Sheng-Che; Huang, Chao-Ching; Wu, Chia-Ching

    2015-10-08

    Perinatal cerebral hypoxic-ischemic (HI) injury damages the architecture of neurovascular units (NVUs) and results in neurological disorders. Here, we differentiated adipose-derived stem cells (ASCs) toward the progenitor of endothelial progenitor cells (EPCs) and neural precursor cells (NPCs) via microenvironmental induction and investigated the protective effect by transplanting ASCs, EPCs, NPCs, or a combination of EPCs and NPCs (E+N) into neonatal HI injured rat pups. The E+N combination produced significant reduction in brain damage and cell apoptosis and the most comprehensive restoration in NVUs regarding neuron number, normal astrocytes, and vessel density. Improvements in cognitive and motor functions were also achieved in injured rats with E+N therapy. Synergistic interactions to facilitate transmigration under in vitro hypoxic microenvironment were discovered with involvement of the neuropilin-1 (NRP1) signal in EPCs and the C-X-C chemokine receptor 4 (CXCR4) and fibroblast growth factor receptor 1 (FGFR1) signals in NPCs. Therefore, ASCs exhibit great potential for cell sources in endothelial and neural lineages to prevent brain from HI damage.

  10. Generation of Brain Microvascular Endothelial-Like Cells from Human Induced Pluripotent Stem Cells by Co-Culture with C6 Glioma Cells.

    Science.gov (United States)

    Minami, Haruka; Tashiro, Katsuhisa; Okada, Atsumasa; Hirata, Nobue; Yamaguchi, Tomoko; Takayama, Kazuo; Mizuguchi, Hiroyuki; Kawabata, Kenji

    2015-01-01

    The blood brain barrier (BBB) is formed by brain microvascular endothelial cells (BMECs) and tightly regulates the transport of molecules from blood to neural tissues. In vitro BBB models from human pluripotent stem cell (PSCs)-derived BMECs would be useful not only for the research on the BBB development and function but also for drug-screening for neurological diseases. However, little is known about the differentiation of human PSCs to BMECs. In the present study, human induced PSCs (iPSCs) were differentiated into endothelial cells (ECs), and further maturated to BMECs. Interestingly, C6 rat glioma cell-conditioned medium (C6CM), in addition to C6 co-culture, induced the differentiation of human iPSC-derived ECs (iPS-ECs) to BMEC-like cells, increase in the trans-endothelial electrical resistance, decreased in the dextran transport and up-regulation of gene expression of tight junction molecules in human iPS-ECs. Moreover, Wnt inhibitors attenuated the effects of C6CM. In summary, we have established a simple protocol of the generation of BMEC-like cells from human iPSCs, and have demonstrated that differentiation of iPS-ECs to BMEC-like cells is induced by C6CM-derived signals, including canonical Wnt signals.

  11. Generation of Brain Microvascular Endothelial-Like Cells from Human Induced Pluripotent Stem Cells by Co-Culture with C6 Glioma Cells.

    Directory of Open Access Journals (Sweden)

    Haruka Minami

    Full Text Available The blood brain barrier (BBB is formed by brain microvascular endothelial cells (BMECs and tightly regulates the transport of molecules from blood to neural tissues. In vitro BBB models from human pluripotent stem cell (PSCs-derived BMECs would be useful not only for the research on the BBB development and function but also for drug-screening for neurological diseases. However, little is known about the differentiation of human PSCs to BMECs. In the present study, human induced PSCs (iPSCs were differentiated into endothelial cells (ECs, and further maturated to BMECs. Interestingly, C6 rat glioma cell-conditioned medium (C6CM, in addition to C6 co-culture, induced the differentiation of human iPSC-derived ECs (iPS-ECs to BMEC-like cells, increase in the trans-endothelial electrical resistance, decreased in the dextran transport and up-regulation of gene expression of tight junction molecules in human iPS-ECs. Moreover, Wnt inhibitors attenuated the effects of C6CM. In summary, we have established a simple protocol of the generation of BMEC-like cells from human iPSCs, and have demonstrated that differentiation of iPS-ECs to BMEC-like cells is induced by C6CM-derived signals, including canonical Wnt signals.

  12. High-Dose Chemotherapy with Autologous Hematopoietic Stem-Cell Rescue for Pediatric Brain Tumor Patients: A Single Institution Experience from UCLA

    Directory of Open Access Journals (Sweden)

    Eduard H. Panosyan

    2011-01-01

    Full Text Available Background. Dose-dependent response makes certain pediatric brain tumors appropriate targets for high-dose chemotherapy with autologous hematopoietic stem-cell rescue (HDCT-AHSCR. Methods. The clinical outcomes and toxicities were analyzed retrospectively for 18 consecutive patients ≤19 y/o treated with HDCT-AHSCR at UCLA (1999–2009. Results. Patients' median age was 2.3 years. Fourteen had primary and 4 recurrent tumors: 12 neural/embryonal (7 medulloblastomas, 4 primitive neuroectodermal tumors, and a pineoblastoma, 3 glial/mixed, and 3 germ cell tumors. Eight patients had initial gross-total and seven subtotal resections. HDCT mostly consisted of carboplatin and/or thiotepa ± etoposide (n=16. Nine patients underwent a single AHSCR and nine ≥3 tandems. Three-year progression-free and overall survival probabilities were 60.5% ± 16 and 69.3% ± 11.5. Ten patients with pre-AHSCR complete remissions were alive/disease-free, whereas 5 of 8 with measurable disease were deceased (median followup: 2.3 yrs. Nine of 13 survivors avoided radiation. Single AHSCR regimens had greater toxicity than ≥3 AHSCR (P<.01. Conclusion. HDCT-AHSCR has a definitive, though limited role for selected pediatric brain tumors with poor prognosis and pretransplant complete/partial remissions.

  13. 伴有脑干萎缩的肝豆状核变性的临床特征%Clinical features in patient with Wilson’s disease plus brain stem atrophy

    Institute of Scientific and Technical Information of China (English)

    杨颖; 吴中亮; 王康军; 刘学东; 王衡; 马磊

    2014-01-01

    Objective To investigate the incidence and clinical features of patients with Wilson’s disease (WD) plus brain stem atrophy. Methods Reviewing clinical manifestations, laboratory tests and neuroimaging data of WD patients admitted in our department and analyzing the clinical features in patient with WD plus brain stem atrophy. Results Cranial MRI or CT showed intracranial abnormal signal in 50 cases with WD, mainly involving the bilateral lenticular nucleus, caudate nucleus, thalamus, cerebel um and brain stem.12 cases with generalized brain atrophy, 6 cases associated with cerebel ar atrophy, 6 cases with brain stem atrophy (pons was more evident), and 2 case meet the imaging criterion of cerebel opontine olive atrophy. The incidence of bulbar palsy (25%), pyramidal tract signs (50%), and nystagmus (25%) in patients with brain stem atrophy has a elevated tendency. However, no significant differences in the course of the disease, ceruloplasmin, serum copper are observed WD patients in with brain stem atrophy. Conclusion Brain stem atrophy is not uncommon in WD patients. These patients are more associated with signs and symptoms of brain stem damage. Some patients maybe frequently misdiagnosed.%目的:探讨肝豆状核变性(WD)患者脑干萎缩的发生率及其临床特征。方法:回顾我科收治的WD患者的临床表现、实验室检查及神经影像学等资料,分析伴有脑干萎缩的WD患者的临床特征。结果:50例患者的头颅MRI或CT均提示颅内出现异常信号,主要累及双侧豆状核、尾状核、丘脑、小脑和脑干。12例伴有广泛大脑萎缩,6例伴有小脑萎缩,6例伴有脑干萎缩(均以桥脑为著),2例影像学符合桥脑小脑橄榄萎缩。伴有脑干萎缩的患者球麻痹(25%)、锥体束征(50%)、眼震(25%)的发生率有升高的趋势,而病程、铜蓝蛋白、血清铜与不伴有脑干萎缩的患者无明显差异(P>0.05)。结论:脑干萎缩在WD患者

  14. 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 ...

  15. Magnetic resonance imaging tracing of transplanted bone marrow mesenchymal stem cells in a rat model of cardiac arrest-induced global brain ischemia

    Institute of Scientific and Technical Information of China (English)

    Yue Fu; Xiangshao Fang; Tong Wang; Jiwen Wang; Jun Jiang; Zhigang Luo; Xiaohui Duan; Jun Shen; Zitong Huang

    2009-01-01

    BACKGROUND: Numerous studies have shown that magnetic resonance imaging (MRI) can detect survival and migration of super paramagnetic iron oxide-labeled stem cells in models of focal cerebral infarction. OBJECTIVE: To observe distribution of bone marrow mesenchymal stem cells (BMSCs) in a rat model of global brain ischemia following cardiac arrest and resuscitation, and to investigate the feasibility of tracing iron oxide-labeled BMSCs using non-invasive MRI. DESIGN, TIME AND SETTING: The randomized, controlled, molecular imaging study was performed at the Linbaixin Medical Research Center, Second Affiliated Hospital, Sun Yat-sen University, and the Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, China from October 2006 to February 2009.MATERIALS: A total of 40 clean, Sprague Dawley rats, aged 6 weeks and of either gender, were supplied by the Experimental Animal Center, Sun Yat-sen University, China, for isolation of BMSCs. Feridex (iron oxide), Gyroscan Inetra 1.5T MRI system, and cardiopulmonary resuscitation device were used in this study. METHODS: A total of 30 healthy, male Sprague Dawley rats, aged 6 months, were used to induce ventricular fibrillation using alternating current. After 8 minutes, the rats underwent 6-minute chest compression and mechanical ventilation, followed by electric defibrillation, to establish rat models of global brain ischemia due to cardiac arrest and resuscitation. A total of 24 successful models were randomly assigned to Feridex-labeled and non-labeled groups (n=12 for each group). At 2 hours after resuscitation, 5 x 10 6 Feddex-labeled BMSCs, with protamine sulfate as a carrier, and 5 × 10 6 non-labeled BMSCs were respectively transplanted into both groups of rats through the right carotid artery (cells were harvested in 1 mL phosphate buffered saline). MAIN OUTCOME MEASURES: Feridex-labeled BMSCs were observed by Prussian blue staining and electron microscopy. Signal intensity, celluar viability

  16. Brain-derived neurotrophic factor gene delivery in an animal model of multiple sclerosis using bone marrow stem cells as a vehicle.

    Science.gov (United States)

    Makar, Tapas K; Bever, Christopher T; Singh, Ishwar S; Royal, Walter; Sahu, Surasri Nandan; Sura, Tushar P; Sultana, Shireen; Sura, Karna T; Patel, Niraj; Dhib-Jalbut, Suhayl; Trisler, David

    2009-05-29

    Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is neuroprotective in animal models of neurodegenerative diseases. However, BDNF has a short half-life and its efficacy in the central nervous system (CNS), when delivered peripherally, is limited due to the blood-brain barrier (BBB). We have developed a means of delivering BDNF into the CNS using genetically engineered bone marrow stem cells (BMSCs) as a vehicle, and have explored the clinical effects of BDNF on outcomes in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). BDNF-engineered-BMSCs were transplanted (i.v.) into irradiated 2-week-old SJL/J female mice. Eight weeks after transplantation, mice were immunized with a peptide of proteolipid protein (PLP(139-151)). Mice, which had received BDNFengineered BMSCs, showed a significant delay in EAE onset and a reduction in overall clinical severity compared to mice receiving BMSC transfected with an empty vector lacking the BDNF gene. In addition, pathological examination showed that BDNF delivery reduced demyelination and increased remyelination. Inhibition of pro-inflammatory cytokines TNF-alpha and IFN-gamma and enhanced expression of the antiinflammatory cytokines IL-4, IL-10, and IL-11 were found in the CNS tissues of the BDNF transplanted group. These results support the use of BMSCs as vehicles to deliver BDNF into the CNS of EAE animals. This is a potentially novel therapeutic approach that might be used to deliver BDNF gene or genes for other therapeutic proteins into the CNS in MS or in other diseases of the CNS in which accessibility of therapeutic proteins is limited due to the BBB.

  17. Brain derived neurotrophic factor and trk B mRNA expression in the brain of a brain stem-spinal cord regenerating model, the European eel, after spinal cord injury.

    Science.gov (United States)

    Dalton, Victoria S; Roberts, Barry L; Borich, Suzanne M

    2009-09-25

    Evidence from mammalian studies suggests that brain derived neurotrophic factor (BDNF) and its receptor, trk B, are upregulated in neuronal cell bodies after injury. Although fish possess neurotrophins and display rapid functional and morphological recovery after central nervous system (CNS) injury, to date few studies have examined neurotrophin expression during CNS regeneration. In this study, RT-PCR was used to investigate the effect of complete spinal cord transection on the mRNA expression of BDNF and its receptor, trk B, in the eel brain at a range of timepoints after injury. The spatial expression pattern of BDNF mRNA in the brain was also assessed before and after injury using in situ hybridization. Marked changes in BDNF and trk B mRNA levels in the eel brain were not detected during the recovery period after cord transection. In addition, the spatial expression pattern of BDNF mRNA in the eel brain appeared unchanged after injury. Our results are in contrast with the increase reported in mammals but are in line with studies examining neurotrophin expression during CNS regeneration in other anamniotic vertebrates.

  18. 脑肿瘤干细胞来源及表面标记物研究的新进展%Progress in the source and surface markers of brain tumor stem cells

    Institute of Scientific and Technical Information of China (English)

    邱实; 谭晓华; 黄辉

    2012-01-01

    BACKGROUND: With the study of brain tumors, researchers have found that brain tumor stem cells (BTSCs) play an important role in tumor growth, development, recurrence and metastasis.OBJECTIVE: To review the source, biological characters and research progress of BCTCs.METHODS: The Wanfang database and ELSEVIER database were used to search the related articles about BTCTs published between January 1998 and January 2010 with the key words of "brain tumor stem cells" in Chinese and "brain tumor stem cells, BTCTs" in English. Totally 198 literatures were screened out, and finally 25 important articles were selected to review according to the inclusion criteria.RESULTS AND CONCLUSION: BTCTs may originate from mutation of neural stem cells, BTCTs have the character of self-renewal, multi-differentiation potency. CD133 and Nestin is the surface biomarker of BTCTs that has been widely used. Study of BTCTs is helpful to clarify the growth mechanism, biological character, clinical treatment and prognosis analysis of the brain tumor.%背景:随着对脑肿瘤研究逐步深化,肿瘤干细胞被发现在肿瘤生长、发展、复发和转移中起着不可或缺的独特作用.目的:综述脑肿瘤干细胞的来源、生物学特性以及研究进展.方法:应用计算机检索1998-01/2010-01万方数据库相关文章,检索词"脑肿瘤干细胞",并限定文章语言种类为中文.同时计算机检索1998-01/2010-01 ELSEVIER数据库相关文章,检索词"brain tumor stem cells,BTCTs",并限定文章语言种类为English.共检索到文献198篇,最终纳入符合标准的文献21篇.结果与结论:脑肿瘤干细胞可能来源于神经干细胞的突变,具有自我更新和多向分化潜能,CD133和Nestin是目前应用得最多的肿瘤干细胞表面标记物,脑肿瘤干细胞的研究对阐明脑肿瘤发生机制、生物学行为及临床治疗、预后判断都具有重要意义.

  19. TiO2-Nanowired Delivery of Mesenchymal Stem Cells Thwarts Diabetes- Induced Exacerbation of Brain Pathology in Heat Stroke: An Experimental Study in the Rat Using Morphological and Biochemical Approaches.

    Science.gov (United States)

    Sharma, Hari S; Feng, Lianyuan; Lafuente, José V; Muresanu, Dafin F; Tian, Zhenrong R; Patnaik, Ranjana; Sharma, Aruna

    2015-01-01

    We have shown previously that heat stroke produced by whole body hyperthermia (WBH) for 4 h at 38°C in diabetic rats exacerbates blood-brain barrier breakdown, brain edema formation and neuronal cell injury as compared to healthy animals after identical heat exposure. In this combination of diabetes and WBH, normal therapeutic measures do not induce sufficient neuroprotection. Thus, we investigated whether nanowired mesenchymal cells (MSCs) when delivered systemically may have better therapeutic effects on brain damage in diabetic rats after WBH. Diabetes induced by streptozotocin administration (75 mg/kg, i.p, daily for 3 days) in rats resulted in clinical symptoms of the disease within 4 to 6 weeks (blood glucose level 20 to 30 mmoles/l as compared to saline control groups (4 to 6 mmoles/l). When subjected to WBH, these diabetic rats showed a 4-to 6-fold exacerbation of blood-brain barrier breakdown to Evans blue and radioiodine, along with brain edema formation and neuronal cell injury. Intravenous administration of rat MSCs (1x10(6)) to diabetic rats one week before WBH slightly reduced brain pathology, whereas TiO2 nanowired MSCs administered in an identical manner resulted in almost complete neuroprotection. On the other hand, MSCs alone significantly reduced brain pathology in saline-treated rats after WBH. These observations indicate that nanowired delivery of stem cells has superior therapeutic potential in heat stroke with diabetes, pointing to novel clinical perspectives in the future.

  20. Spinal projections from the lower brain stem in the cat as demonstrated by the horseradish peroxidase technique. II. Projections from the dorsolateral pontine tegmentum and raphe nuclei.

    Science.gov (United States)

    Tohyama, M; Sakai, K; Touret, M; Salvert, D; Jouvet, M

    1979-11-02

    The descending projections to the spinal cord arising from the dorsolateral pontine tegmentum and brain stem raphe nuclei have been investigated by means of the horseradish peroxidase (HRP) technique. Particular attention was taken to clarify the cells of origin and the funicular trajectory of these spinal projections. After injections of HRP into the spinal cord, a significant of HRP labeled neurons were observed in the following dorsolateral pontine tegmental structures: (1) an area ventral to the nucleus cuneiformis; (2) principal locus coeruleus; (3) locus coeruleus a; (4) locuse subcoeruleus; (5) Kölliker-Fuse nucleus; and (6) nucleus parabrachialis lateralis. As a rule, the projections are ipsilateral and descendaphe-spinal projections, we have demonstrated that the nucleus raphe dorsalis also sends axons to the cervical segment of the spinal cord. Furthermore, in accord with previous reports, HRP labeled cells were also identified in the nucleus raphe magnus, pallidus and obscurus, but not in the nucleus raphe centralis superior and pontis. On the whole the present study further clarified the organization of spinal projections from the dorsolateral pons and raphe nuclei and provided some additional anatomical data for the physiology of the tegmentospinal and raphe-spinal projections.

  1. Chemo-predictive assay for targeting cancer stem-like cells in patients affected by brain tumors.

    Directory of Open Access Journals (Sweden)

    Sarah E Mathis

    Full Text Available Administration of ineffective anticancer therapy is associated with unnecessary toxicity and development of resistant clones. Cancer stem-like cells (CSLCs resist chemotherapy, thereby causing relapse of the disease. Thus, development of a test that identifies the most effective chemotherapy management offers great promise for individualized anticancer treatments. We have developed an ex vivo chemotherapy sensitivity assay (ChemoID, which measures the sensitivity of CSLCs as well as the bulk of tumor cells to a variety of chemotherapy agents. Two patients, a 21-year old male (patient 1 and a 5-month female (patient 2, affected by anaplastic WHO grade-III ependymoma were screened using the ChemoID assay. Patient 1 was found sensitive to the combination of irinotecan and bevacizumab, which resulted in a prolonged disease progression free period of 18 months. Following recurrence, the combination of various chemotherapy drugs was tested again with the ChemoID assay. We found that benzyl isothiocyanate (BITC greatly increased the chemosensitivity of the ependymoma cells to the combination of irinotecan and bevacizumab. After patient 1 was treated for two months with irinotecan, bevacizumab and supplements of cruciferous vegetable extracts containing BITC, we observed over 50% tumoral regression in comparison with pre-ChemoID scan as evidenced by MRI. Patient 2 was found resistant to all treatments tested and following 6 cycles of vincristine, carboplatin, cyclophosphamide, etoposide, and cisplatin in various combinations, the tumor of this patient rapidly progressed and proton beam therapy was recommended. As expected animal studies conducted with patient derived xenografts treated with ChemoID screened drugs recapitulated the clinical observation. This assay demonstrates that patients with the same histological stage and grade of cancer may vary considerably in their clinical response, suggesting that ChemoID testing which measures the sensitivity

  2. Neural differentiation of brain-derived neurotrophic factor-expressing human umbilical cord blood-derived mesenchymal stem cells in culture via TrkB-mediated ERK and β-catenin phosphorylation and following transplantation into the developing brain.

    Science.gov (United States)

    Lim, Jung Yeon; Park, Sang In; Kim, Seong Muk; Jun, Jin Ae; Oh, Ji Hyeon; Ryu, Chung Hun; Jeong, Chang Hyun; Park, Sun Hwa; Park, Soon A; Oh, Wonil; Chang, Jong Wook; Jeun, Sin-Soo

    2011-01-01

    The ability of mesenchymal stem cells (MSCs) to differentiate into neural cells makes them potential replacement therapeutic candidates in neurological diseases. Presently, overexpression of brain-derived neurotrophic factor (BDNF), which is crucial in the regulation of neural progenitor cell differentiation and maturation during development, was sufficient to convert the mesodermal cell fate of human umbilical cord blood-derived MSCs (hUCB-MSCs) into a neuronal fate in culture, in the absence of specialized induction chemicals. BDNF overexpressing hUCB-MSCs (MSCs-BDNF) yielded an increased number of neuron-like cells and, surprisingly, increased the expression of neuronal phenotype markers in a time-dependent manner compared with control hUCB-MSCs. In addition, MSCs-BDNF exhibited a decreased labeling for MSCs-related antigens such as CD44, CD73, and CD90, and decreased potential to differentiate into mesodermal lineages. Phosphorylation of the receptor tyrosine kinase B (TrkB), which is a receptor of BDNF, was increased significantly in MSC-BDNF. BDNF overexpression also increased the phosphorylation of β-catenin and extracellular signal-regulated kinases (ERKs). Inhibition of TrkB availability by treatment with the TrkB-specific inhibitor K252a blocked the BDNF-stimulated phosphorylation of β-catenin and ERKs, indicating the involvement of both the β-catenin and ERKs signals in the BDNF-stimulated and TrkB-mediated neural differentiation of hUCB-MSCs. Reduction of β-catenin availability using small interfering RNA-mediated gene silencing inhibited ERKs phosphorylation. However, β-catenin activation was maintained. In addition, inhibition of β-catenin and ERKs expression levels abrogated the BDNF-stimulated upregulation of neuronal phenotype markers. Furthermore, MSC-BDNF survived and migrated more extensively when grafted into the lateral ventricles of neonatal mouse brain, and differentiated significantly into neurons in the olfactory bulb and

  3. Intracerebroventricular transplanted bone marrow stem cells survive and migrate into the brain of rats with Parkinson’s disease

    Institute of Scientific and Technical Information of China (English)

    Ping Gu; Zhongxia Zhang; Dongsheng Cui; Yanyong Wang; Lin Ma; Yuan Geng; Mingwei Wang

    2012-01-01

    In this study, 6-hydroxydopamine was stereotaxically injected into the right substantia nigra compact and ventral tegmental area of rats to establish Parkinson’s disease models. The rats then received a transplantation of bone marrow stromal cells that were previously isolated, cultured and labeled with 5-bromo-2’-deoxyuridine in vitro. Transplantation of the bone marrow stromal cells significantly decreased apomorphine-induced rotation time and the escape latency in the Morris water maze test as compared with rats with untreated Parkinson’s disease. Immunohistochemical staining showed that, 5-bromo-2’-deoxyuridine-immunoreactive cells were present in the lateral ventricular wall and the choroid plexus 1 day after transplantation. These immunoreactive cells migrated to the surrounding areas of the lateral cerebral ventricle along the corpus callosum. The results indicated that bone marrow stromal cells could migrate to tissues surround the cerebral ventricle via the cerebrospinal fluid circulation and fuse with cells in the brain, thus altering the phenotype of cells or forming neuron-like cells or astrocytes capable of expressing neuron-specific proteins. Taken together, the present findings indicate that bone marrow stromal cells transplanted intracerebroventricularly could survive, migrate and significantly improve the rotational behavior and cognitive function of rats with experimentally induced Parkinson’s disease.

  4. In vivo tracing of superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells transplanted for traumatic brain injury by susceptibility weighted imaging in a rat model

    Institute of Scientific and Technical Information of China (English)

    CHENG Jing-liang; YANG Yun-jun; LI Hua-li; WANG Juan; WANG Mei-hao; ZHANG Yong

    2010-01-01

    Objective:To label rat bone marrow mesenchymal stem cells (BMSCs) with superparamagnetic iron oxide (SPIO) in vitro, and to monitor the survival and location of these labeled BMSCs in a rat model of traumatic brain injury (TBI) by susceptibility weighted imaging (SWI)sequence.Methods:BMSCs were cultured in vitro and then labeled with SPIO. Totally 24 male Sprague Dawley (SD) rats weighing 200-250 g were randomly divided into 4 groups: Groups A-D (n=6 for each group). Moderate TBI models of all the rats were developed in the left hemisphere following Feeney's method. Group A was the experimental group and stereotaxic transplantation of BMSCs labeled with SPIO into the region nearby the contusion was conducted in this group 24 hours after TBI modeling. The other three groups were control groups with transplantation of SPIO, unlabeled BMSCs and injection of nutrient solution respectively conducted in Groups B, C and D at the same time. Monitoring of these SPIO-labeled BMSCs by SWI was performed one day,one week and three weeks after implantation.Results: Numerous BMSCs were successfully labeled with SPIO. They were positive for Prussian blue staining and intracytoplasm positive blue stained particles were found under a microscope (×200). Scattered little iron particles were observed in the vesicles by electron microscopy (×5000). MRI of the transplantation sites of the left hemisphere demonstrated a low signal intensity on magnitude images,phase images and SWI images for all the test rats in Group A, and the lesion in the left parietal cortex demonstrated a semicircular low intensity on SWI images, which clearly showed the distribution and migration of BMSCs in the first and third weeks. For Group B, a low signal intensity by MRI was only observed on the first day but undetected during the following examination. No signals were observed in Groups C and D at any time points.Conclusion:SWI sequence in vivo can consecutively and noninvasively trace and demonstrate the

  5. Lead induces similar gene expression changes in brains of gestationally exposed adult mice and in neurons differentiated from mouse embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Francisco Javier Sánchez-Martín

    Full Text Available Exposure to environmental toxicants during embryonic life causes changes in the expression of developmental genes that may last for a lifetime and adversely affect the exposed individual. Developmental exposure to lead (Pb, an ubiquitous environmental contaminant, causes deficits in cognitive functions and IQ, behavioral effects, and attention deficit hyperactivity disorder (ADHD. Long-term effects observed after early life exposure to Pb include reduction of gray matter, alteration of myelin structure, and increment of criminal behavior in adults. Despite growing research interest, the molecular mechanisms responsible for the effects of lead in the central nervous system are still largely unknown. To study the molecular changes due to Pb exposure during neurodevelopment, we exposed mice to Pb in utero and examined the expression of neural markers, neurotrophins, transcription factors and glutamate-related genes in hippocampus, cortex, and thalamus at postnatal day 60. We found that hippocampus was the area where gene expression changes due to Pb exposure were more pronounced. To recapitulate gestational Pb exposure in vitro, we differentiated mouse embryonic stem cells (ESC into neurons and treated ESC-derived neurons with Pb for the length of the differentiation process. These neurons expressed the characteristic neuronal markers Tubb3, Syp, Gap43, Hud, Ngn1, Vglut1 (a marker of glutamatergic neurons, and all the glutamate receptor subunits, but not the glial marker Gafp. Importantly, several of the changes observed in Pb-exposed mouse brains in vivo were also observed in Pb-treated ESC-derived neurons, including those affecting expression of Ngn1, Bdnf exon IV, Grin1, Grin2D, Grik5, Gria4, and Grm6. We conclude that our ESC-derived model of toxicant exposure during neural differentiation promises to be a useful model to analyze mechanisms of neurotoxicity induced by Pb and other environmental agents.

  6. Association between Toll-Like Receptor 4 Expression and Neural Stem Cell Proliferation in the Hippocampus Following Traumatic Brain Injury in Mice

    Directory of Open Access Journals (Sweden)

    Yuqin Ye

    2014-07-01

    Full Text Available Whether or how neural stem cells (NSCs respond to toll-like receptor 4 (TLR4 in an inflammatory environment caused by traumatic brain injury (TBI has not been understood. In the present study, association between TLR4 expression and NSCs proliferation in the hippocampus was investigated in a mouse model of TBI using controlled cortical impact (CCI. Hippocampal proliferating cells were labeled with the thymidine analog 5-bromo-2-deoxyuridine (BrdU. In order to identify NSCs, the proliferating cells were further co-labeled with BrdU/sex determination region of Y chromosome related high mobility group box gene 2 (SOX2. Morphological observation on the expression of BrdU, SOX2, and TLR4 in the hippocampus was performed by inmmunofluorescence (IF. Relative quantification of TLR4 expression at the protein and mRNA level was performed using Western blotting and real-time polymerase chain reaction (PCR. It was observed that BrdU+/SOX2+cells accounted for 95.80% ± 7.91% among BrdU+ cells; several BrdU+ cells and SOX2+ cells in the hippocampus were also TLR4-positive post injury, and that BrdU+ cell numbers, together with TLR4 expression at either protein or mRNA level, increased significantly in TBI mice over 1, 3, 7, 14, and 21 days survivals and changed in a similar temporal pattern with a peak at 3 day post-injury. These results indicate that hippocampal proliferating cells (suggestive of NSCs expressed TLR4, and that there was a potential association between increased expression of TLR4 and the proliferation of NSCs post TBI. It is concluded that hippocampal TLR4 may play a potential role in endogenous neurogenesis after TBI.

  7. Pro-life role for c-Jun N-terminal kinase and p38 mitogen-activated protein kinase at rostral ventrolateral medulla in experimental brain stem death

    Directory of Open Access Journals (Sweden)

    Chang Alice YW

    2012-11-01

    Full Text Available Abstract Background Based on an experimental brain stem death model, we demonstrated previously that activation of the mitogen-activated protein kinase kinase 1/2 (MEK1/2/extracellular signal-regulated kinase 1/2 (ERK1/2/mitogen-activated protein kinase signal-interacting kinase 1/2 (MNK1/2 cascade plays a pro-life role in the rostral ventrolateral medulla (RVLM, the origin of a life-and-death signal detected from systemic arterial pressure, which sequentially increases (pro-life and decreases (pro-death to reflect progressive dysfunction of central cardiovascular regulation during the advancement towards brain stem death in critically ill patients. The present study assessed the hypothesis that, in addition to ERK1/2, c-Jun NH2-terminal kinase (JNK and p38 mitogen-activated protein kinase (p38MAPK, the other two mammalian members of MAPKs that are originally identified as stress-activated protein kinases, are activated specifically by MAPK kinase 4 (MAP2K4 or MAP2K6 and play a pro-life role in RVLM during experimental brain stem death. We further delineated the participation of phosphorylating activating transcriptional factor-2 (ATF-2 and c-Jun, the classical transcription factor activated by JNK or p38MAPK, in this process. Results An experimental model of brain stem death that employed microinjection of the organophosphate insecticide mevinphos (Mev; 10 nmol bilaterally into RVLM of Sprague–Dawley rats was used, alongside cardiovascular, pharmacological and biochemical evaluations. Results from ELISA showed that whereas the total JNK, p38MAPK, MAP2K4 and MAP2K6 were not affected, augmented phosphorylation of JNK at Thr183 and Tyr185 and p38MAPK at Thr180 and Tyr182, accompanied by phosphorylation of their upstream activators MAP2K4 at Ser257 and Thr261 and MAP2K6 at Ser207 and Thr211 in RVLM occurred preferentially during the pro-life phase of experimental brain stem death. Moreover, the activity of transcription factors ATF-2 at Thr71 and

  8. Reactive ability of nerve stem cell to ischemic brain injury%神经干细胞对缺血性脑损伤的反应能力

    Institute of Scientific and Technical Information of China (English)

    徐曦; 肖新莉; 罗秀成; 杨世照; 李保利; 刘勇

    2006-01-01

    BACKGROUND: When central nervous system is injured, re-expression of nestin protein may enhance the anti-injury ability of cells and be advantageous to the repair of focus of injury.OBJECTIVE: To explore the reaction of nerve stem cell (NSC) in permanent brain ischemia through NSC migration and the change of nestin protein expression.DESIGN: A randomized and controlled verification research with experimental animals as subjects.SETTING: Anatomy teaching and research offices in a training school and a university.MATERIALS: The experiment was done in the Teaching and Research Office of Humane Anatomy in Medical College of Xi'an Jiaotong University from October 1999 to January 2001. Totally 75 healthy SD rats were selected and randomly divided into normal control group, experiment group and sham-operation group. Twenty-five animals were in each group. Heads of animals were cut and brain was got out at the 1st, 3rd, 7th, 14th and 28thdays after operation, 5 animals at each time.METHODS: The model was rats with permanent cerebral ischemia. Immunohistochemical dyeing methods were used to observe NSC migration,change of marker of NSC and nestin protein at the 1st, 3rd, 7th, 14th and 28th day after cerebral ischemia.MAIN OUTCOME MEASURES: ①Results of immunohostochemicaldyeing. ②Migration length of nestin+ cells in anterior subentricular zone (SZa) region of brain tissue at normal status and at different time points after cerebral ischemia. ③Number variation of nestin+ cells at different timepoits after ischemia near the ischemic region.RESULTS: Through nestin immunohistochemical dyeing, it was found that NSC in normal brain tissue mainly existed in subependymal zone (SEZ)region. NSC of SEZ migrated in the direction of ischemic region along ventri- corpus callosum after ischemia. Among them, it reached the farthest at the 7th day after ischemia. More nestin+ cells appeared near ischemic region at the 1st day, and then reduced little by little 3 days later

  9. Cholera toxin regulates a signaling pathway critical for the expansion of neural stem cell cultures from the fetal and adult rodent brains.

    Directory of Open Access Journals (Sweden)

    Andreas Androutsellis-Theotokis

    Full Text Available BACKGROUND: New mechanisms that regulate neural stem cell (NSC expansion will contribute to improved assay systems and the emerging regenerative approach that targets endogenous stem cells. Expanding knowledge on the control of stem cell self renewal will also lead to new approaches for targeting the stem cell population of cancers. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that Cholera toxin regulates two recently characterized NSC markers, the Tie2 receptor and the transcription factor Hes3, and promotes the expansion of NSCs in culture. Cholera toxin increases immunoreactivity for the Tie2 receptor and rapidly induces the nuclear localization of Hes3. This is followed by powerful cultured NSC expansion and induction of proliferation both in the presence and absence of mitogen. CONCLUSIONS/SIGNIFICANCE: Our data suggest a new cell biological mechanism that regulates the self renewal and differentiation properties of stem cells, providing a new logic to manipulate NSCs in the context of regenerative disease and cancer.

  10. Distribution of somatostatin immunoreactive products in the brain stem auditory center of guinea pigs%豚鼠脑干听觉中枢生长抑素免疫反应产物的分布

    Institute of Scientific and Technical Information of China (English)

    王唯析; 赵明光; 胡海涛; 许珉; 马惠芳; 任惠民

    2000-01-01

    Objective To research the distribution and significance of somatostatin(SS) in the brain stem auditory centre of guinea pigs. Methods The distribution of SS positive products in the cochlear nucleus(CN), superior olivary complex(SOC) and the inferior colliculus(IC) of the brain stem auditory centre of guinea pigs was investigated with immunohistochemical ABC method.Results The SS positive neurons, fibers and terminals were widely distributed in the brain stem auditory center. The SS positive neurons were mainly distributed in the ventral cochlear nucleus (VCN), nucleus of the trapezoid body(NTB), medial superior olive(MSO) and paraolivary nucleus (PON). The high density of SS-immunoreactive fibers and terminals was observed in the nucleus of IC, lateral superior olive(LSO) and dorsal cochlear nucleus(DCN). Conclusion The SS may participate in transmitting and regulating sound messages in brain stem auditory center of guinea pigs.%目的研究生长抑素(SS)在豚鼠脑干听觉中枢的分布及意义。方法采用免疫组化ABC法观察了豚鼠脑干听觉中枢的耳蜗核(CN)、上橄榄核簇(SOC)及下丘(IC)内SS免疫反应阳性产物的分布。结果在脑干听觉中枢广泛分布着SS阳性神经元、纤维及终末。SS阳性神经元主要分布在蜗神经腹核(VCN)、斜方体核(NTB)、内侧上橄榄核(MSO)及橄榄周核(PON),而SS阳性纤维及终末主要分布在下丘、外侧上橄榄核(LSO)及蜗神经背核(DCN)。结论脑干听觉中枢内的SS参与声信号的传递与调控。

  11. Selection of reference genes for normalisation of real-time RT-PCR in brain-stem death injury in Ovis aries

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    Fraser John F

    2009-07-01

    Full Text Available Abstract Background Heart and lung transplantation is frequently the only therapeutic option for patients with end stage cardio respiratory disease. Organ donation post brain stem death (BSD is a pre-requisite, yet BSD itself causes such severe damage that many organs offered for donation are unusable, with lung being the organ most affected by BSD. In Australia and New Zealand, less than 50% of lungs offered for donation post BSD are suitable for transplantation, as compared with over 90% of kidneys, resulting in patients dying for lack of suitable lungs. Our group has developed a novel 24 h sheep BSD model to mimic the physiological milieu of the typical human organ donor. Characterisation of the gene expression changes associated with BSD is critical and will assist in determining the aetiology of lung damage post BSD. Real-time PCR is a highly sensitive method involving multiple steps from extraction to processing RNA so the choice of housekeeping genes is important in obtaining reliable results. Little information however, is available on the expression stability of reference genes in the sheep pulmonary artery and lung. We aimed to establish a set of stably expressed reference genes for use as a standard for analysis of gene expression changes in BSD. Results We evaluated the expression stability of 6 candidate normalisation genes (ACTB, GAPDH, HGPRT, PGK1, PPIA and RPLP0 using real time quantitative PCR. There was a wide range of Ct-values within each tissue for pulmonary artery (15–24 and lung (16–25 but the expression pattern for each gene was similar across the two tissues. After geNorm analysis, ACTB and PPIA were shown to be the most stably expressed in the pulmonary artery and ACTB and PGK1 in the lung tissue of BSD sheep. Conclusion Accurate normalisation is critical in obtaining reliable and reproducible results in gene expression studies. This study demonstrates tissue associated variability in the selection of these

  12. Childhood Brain Stem Glioma Treatment

    Science.gov (United States)

    ... and trouble walking. Vision and hearing problems. Morning headache or headache that goes away after vomiting . Nausea and vomiting. ... Cancer Late Effects of Treatment for Childhood Cancer Adolescents and Young Adults with Cancer Children with Cancer: ...

  13. Human insulin-like growth factor 1-transfected umbilical cord blood neural stem cell transplantation improves hypoxic-ischemic brain injury

    Institute of Scientific and Technical Information of China (English)

    Dengna Zhu; Yanjie Jia; Jun Wang; Boai Zhang; Guohui Niu; Yazhen Fan

    2011-01-01

    Human insulin-like growth factor 1-transfected umbilical cord blood neural stem cells were transplanted into a hypoxic-ischemic neonatal rat model via the tail vein.BrdU-positive cells at day 7post-transplantation,as well as nestin-and neuron specific enolase-positive cells at day 14 wereincreased compared with those of the single neural stem cell transplantation group.In addition,theproportion of neuronal differentiation was enhanced.The genetically modified cell-transplanted ratsexhibited enhanced performance in correctly crossing a Y-maze and climbing an angled slope compared with those of the single neural stem cell transplantation group.These results showed that human insulin-like growth factor 1-transfected neural stem cell transplantation promotes therecovery of the learning,memory and motor functions in hypoxic-ischemic rats.

  14. Culture of Mouse Neural Stem Cell Precursors

    OpenAIRE

    Currle, D. Spencer; Hu, Jia Sheng; Kolski-Andreaco, Aaron; Monuki, Edwin S

    2007-01-01

    Primary neural stem cell cultures are useful for studying the mechanisms underlying central nervous system development. Stem cell research will increase our understanding of the nervous system and may allow us to develop treatments for currently incurable brain diseases and injuries. In addition, stem cells should be used for stem cell research aimed at the detailed study of mechanisms of neural differentiation and transdifferentiation and the genetic and environmental signals that direct the...

  15. 脑干起源肌阵挛模型的建立%Developing an animal model of the brain stem myoclonus

    Institute of Scientific and Technical Information of China (English)

    何志江; 曹洁; 蔡方成; 冯成功; 陈恒胜

    2010-01-01

    Objective To develop experimental animal model of the brain stem myoclonus,which more closely replicate clinic features of mechanism, behavior, neuroelectrophysiology and pharmacodynamics.Methods L-5-HTP (the precursor of L-5-HT)was microinjected into the dorsal pons of young guinea pig to induce myoclonus (electromyogram burst of myoclonus≤400 ms by synchronous recording).Some animals were pretreated with anticonvulsant VPA,CZP or CBZ at effective dose 50 (EC_(50)).Myoclonus was induced when the drug level was within their effective anticonvulsion concentration.The neuroelectrophysiological characteristics of myoclonus including latency,time of reaching its peak,duration of seizure peak,the maximum seizure frequency and total duration were detected.EMG and ictal electroencephalogram(EEG)were recorded synchronously.The origin of myoclonus and its correlation with epileptic discharges were further confirmed by jerk-locked back averaging(JLA).Results (1)L-5-HTP induced pure myoclonus from the dorsal pons of guinea pig permanently(8/every site,the rate of producing myoclonus is 100%).(2)The myoclonus presented bilaterally or as general myoclonus,which was sensitive to tactile and sound sensation.(3)The EMG duration of the myoclonus wag longer((208.75 ± 81.42)ms),and ictal EEG showed scattered and irregular spikes and sharp waves without time-locked correlation with EMG activities.(4)The synchronous ictal EEG of the myoclonus showed spike and sharp waves,but there was no time-locked EEG activity in JLA.(5)In the animals treated with anticonvulsant at EC_(50) concentrations:VPA and CZP decreased the maximum seizure frequency(there are 28.13±3.79 per minutes in VPA group and 37.17±4.67 perminutes in CZP group)and shortened the duration of peak time ((55.00±14.14)minutes in VPA group and(50.00±11.73)minutes in CZP group respectively)and total time(VPA group was(124.17±40.04)minutes and CZP group was(156.88±30.71)minutes)of myoclonus(F value were between 23.41 and

  16. The effect of gender on bone-conduct auditory brain stem response%性别对骨导听性脑干反应的影响

    Institute of Scientific and Technical Information of China (English)

    窦晓宁; 徐荣华; 任雪莲; 王爱婷; 杨燕燕; 张敏敏

    2014-01-01

    Objective To study the difference of bone‐conduct auditory brain stem response (ABR) results between different genders and to provide reference for clinical practice .Methods Bone‐oscillatory is placed on the mastoid portion ,back of the ear and the frontal placement in a group of normal hearing adults .The results of air and bone‐conduct ABR were recorded and analyzed .Results There were no differences for the threshold of air‐conduct and bone‐conduct ABR testing in different placements ( P>0 .05) .Under 30 dBnHL above the threshold , there were no differences forⅠ ,Ⅲ peak latency (PL) of air‐conduct and bone‐conduct ABR between gender( P>0 .05) .There were differences forⅤPL ( P0 .05) .There were differences forⅠ‐ⅤIPL( P<0 .05) . Conclusion There were differences forⅤPL ,Ⅰ‐ⅤIPL of air‐conduct and bone‐conduct ABR between genders .So we should consider the difference of the gender and have normal reference value of different genders.%目的:研究不同性别间骨导听性脑干反应(ABR)结果间的差异性。方法选择听力正常成年人60名(120耳),男性及女性各30名(60耳),将骨导 ABR的振荡器分别放置乳突、耳后、额部,进行骨、气导ABR检测,对检测结果进行性别间比较分析。结果气导及各部位骨导ABR阈值性别间比较,差异无统计学意义( P>0.05)。在阈上30 dBnHL刺激强度下,各部位骨导与气导ABRⅠ、Ⅲ波峰潜伏期(PL)性别间比较,差异均无统计学意义( P >0.05)。各部位骨导与气导ABRⅤ波PL性别间比较,差异均有统计学意义( P <0.05)。气导与各部位骨导Ⅰ~Ⅲ波峰间期(IPL )性别间比较,差异均无统计学意义( P >0.05)。气导与各部位骨导Ⅰ~ⅤIPL性别间比较,差异均有统计学意义( P <0.05)。结论不同性别间骨、气导ABRⅤ波PL及Ⅰ ~ⅤIPL存在差异性,检测时应充分考虑到性别间

  17. 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

    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...... treatment. The overall aim of the present PhD project has been to study the functional role of EGFR and Notch activity in bCSCs stem cell-like features and tumorigenic potential with the purpose of deepen our knowledge about the significance of these pathways in the bCSC population in GBM. By establishing...... and culturing human derived GBM xenograft cells under NSC conditions we obtained neurosphere cultures that contained cells with stem cell-like and tumorigenic properties. We moreover characterized the different cultures based on their expression level of the EGFR and Notch receptor as well as the expression...

  18. Brain-derived neurotrophic factors increase the proliferation and differentiation of endogenous neural stem cells in mouse models of cerebral infarction

    Institute of Scientific and Technical Information of China (English)

    Dawei Zang; Juan Liu; Xianhua Zuo; Surindar Cheema

    2007-01-01

    BACKGROUND: It has been confirmed that brain-derived neurotrophic factor (BDNF) can promote the proliferation of neural stem cells (NSCs) and protect neuron-like cells in vitro. However, its effect on endogenous NSCs in vivo is still unclear.OBJECTIVE: To evaluate whether BDNF can induce the endogenous NSCs to proliferate and differentiate into the neurons in the mice model of cerebral infarction.DESIGN: A synchronal controlled observation.SETTINGS: Department of Neurology, Microbiology Division of the Department of Laboratory, Tianjin First Central Hospital; Howard Florey Institute, Medical College, the University of Melbourne.MATERIALS: Twenty-four pure breed C57BL/6J mice at the age of 10 weeks old (12 males and 12 females)were divided into saline control group and BDNF-treated group, 6 males and 6 females in each group.METHODS: The experiments were performed at the University of Melbourne from July 2004 to February 2005. ① The left middle cerebral artery (MCA) was ligated in both groups to establish models of cerebral infarction and the Matsushita measuring method was used to monitor the blood flow of the lesioned region supplied by MCA. 75% reduction of blood flow should be reached in the lesioned region. ② At 24 hours after infarction, mice in the BDNF-treated group were administrated with BDNF, which was slowly delivered using an ALZET osmium pump design. BDNF was dissolved in saline at the dosage of 500 mg/kg and injected into the pump, which could release the solution consistently in the following 28 days. The mice in the saline control group accepted the same volume of saline at 24 hours after infarction. ③ The Rotarod function test began at 1 week preoperatively, the time stayed on Rotarod was recorded. The mice were tested once a day till the end of the experiment. At 4 weeks post cerebral infarction, double labeling of Nestin and GFAP, BⅢ tubulin and CNPase immunostaining was performed to observe the differentiation directions of the re

  19. Road for understanding cancer stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Erzik, Can

    2007-01-01

    There is increasing evidence suggesting that stem cells are susceptive to carcinogenesis and, consequently, can be the origin of many cancers. Recently, the neoplastic potential of stem cells has been supported by many groups showing the existence of subpopulations with stem cell characteristics...... in tumor biopsies such as brain and breast. Evidence supporting the cancer stem cell hypothesis has gained impact due to progress in stem cell biology and development of new models to validate the self-renewal potential of stem cells. Recent evidence on the possible identification of cancer stem cells may...... offer an opportunity to use these cells as future therapeutic targets. Therefore, model systems in this field have become very important and useful. This review will focus on the state of knowledge on cancer stem cell research, including cell line models for cancer stem cells. The latter will, as models...

  20. Immunomagenetic indirect positive sorting of neural stem cells from fetal rat brain%免疫磁珠法分选胚胎大鼠脑神经干细胞的初步研究

    Institute of Scientific and Technical Information of China (English)

    高国一; 李莉

    2000-01-01

    目的:探索应用免疫磁珠间接阳性法分选神经上皮干细胞蛋白(nestin)阳性的神经干细胞群的实验条件.为研究神经干细胞的特性与神经干细胞的培养和移植研究创造有利条件。方法:制取胎鼠大脑组织细胞悬液,免疫磁珠法分选胎鼠脑神经干细胞,以流式细胞术检测阳性细胞纯度,以锥虫蓝染色法检测细胞活性。结果:该法分选的nestin阳性细胞纯度为93.0%~99.7%,其中活性细胞为92%~97%。结论:免疫磁珠法分离胎鼠脑神经干细胞群落简便、有效,可以为神经干细胞细胞培养和移植提供细胞来源,也为研究高纯度神经干细胞的特性提供了实验基础。%Objective:To study the sorting high-purity neural stem cells fromfetal rat brain cells.Methods:Fetal rat brain cell suspensions were incubated with monoclone antibody of nestin,and the labelled cells were separated from the suspension in the magnetic field by immunobeads coated with the second antibody.Purity of the sorted cells was determined with flow cytometry.Results:Purity of the sorted neural stem cells were determined as 93.0%-99.7%,active cells acount for 92 %-97 %.Conclusion:The magnetic cell sorting system can effectively separate neural stem cell from brain cell suspension.

  1. Types of Stem Cells

    Science.gov (United States)

    ... Stem Cell Glossary Search Toggle Nav Types of Stem Cells Stem cells are the foundation from which all ... Learn About Stem Cells > Types of Stem Cells Stem cells Stem cells are the foundation for every organ ...

  2. A Bio-Acoustic Levitational (BAL) Assembly Method for Engineering of Multilayered, 3D Brain-Like Constructs, Using Human Embryonic Stem Cell Derived Neuro-Progenitors.

    Science.gov (United States)

    Bouyer, Charlène; Chen, Pu; Güven, Sinan; Demirtaş, Tuğrul Tolga; Nieland, Thomas J F; Padilla, Frédéric; Demirci, Utkan

    2016-01-06

    A bio-acoustic levitational assembly method for engineering of multilayered, 3D brainlike constructs is presented. Acoustic radiation forces are used to levitate neuroprogenitors derived from human embryonic stem cells in 3D multilayered fibrin tissue constructs. The neuro-progenitor cells are subsequently differentiated in neural cells, resulting in a 3D neuronal construct with inter and intralayer neurite elongations.

  3. [Cyclothymia and the brain stem. The question of symptomatic cyclothymia on the basis of observations in insufficiency of the basilar arterial system].

    Science.gov (United States)

    Marneros, A; Philipp, M

    1978-01-01

    Seven patients with an insufficiency in the basilar arterial system showed a typical endogenous depression. We assumed that the temporal coincidence of neurological and psychial syndromes was not accidental but both were caused by a circulation disturbance in the cerebral stem structures.

  4. Mechanisms underlying attenuation of apoptosis of cortical neurons in the hypoxic brain by lfavonoids from the stems and leaves of Scutellaria baicalensis Georgi

    Institute of Scientific and Technical Information of China (English)

    Guangxin Miao; Hongxiang Zhao; Ke Guo; Jianjun Cheng; Shufeng Zhang; Xiaofeng Zhang; Zhenling Cai; Hong Miao; Yazhen Shang

    2014-01-01

    Flavonoids from the stems and leaves of Scutellaria baicalensis Georgi, an antioxidant, marked-ly improve memory impairments and neuronal injuries. In the present study, primary cortical neurons of rats were exposed to potassium cyanide to establish a model of in vitro neural cell apoptosis. Inhibition of apoptosis by lfavonoids from the stems and leaves of Scutellaria baical-ensis Georgi at concentrations of 18.98, 37.36, and 75.92μg/mL was detected using this model. These lfavonoids dramatically increased cell survival, inhibited cell apoptosis and excessive pro-duction of malondialdehyde, and increased the activities of superoxide dismutase, glutathione peroxidase, and Na+-K+-ATPase in primary cortical neurons exposed to potassium cyanide. The lfavonoids from the stems and leaves of Scutellaria baicalensis Georgi were originally found to have a polyhydric structure and to protect against cerebral hypoxia in in vitro and in vivo models, including hypoxia induced by potassium cyanide or cerebral ischemia. The present study suggests that lfavonoids from the stems and leaves of Scutellaria baicalensis Georgi exert neuroprotective effects via modulation of oxidative stress, such as malondialdehyde, superoxide dismutase, gluta-thione peroxidase and Na+-K+-ATPase disorders induced by potassium cyanide.

  5. Study on developmental laws of neural stem cells in corpus striatum from the different human fetal brain%不同胎龄脑纹状体神经干细胞的发育规律研究

    Institute of Scientific and Technical Information of China (English)

    尹晓娟; 杜江; 封志纯

    2004-01-01

    BACKGROUND: Therapeutic effect of neural stem cells receives increasingly confirmation in retrogressive diseases of nervous system: however, the develoopmental laws of neural stem cells of different fetal age have not been fully evaluated.OBJECTIVE: To investigate the developmental laws of neural stem cells in corpus striatum from different human fetal brains for expanding clinical applications of neural sten cells in pediatrics fields.DESIGN: A prospective experimental study with non-random inter-control.SETTING and PARTICIPANTS: This study was completed in the Laboratory of Pediatric Center of Military. 30 embryos from induced labor by water bags were obtained from Department of Obstetrics in a certain tertiary hospital in Goangzhou City with the consents from family members or mothers of the fetals. 30 embryos were divided into five groups according to gestational age of 24,26, 28, 30 and 32 weeks with six fetals in each group.INTERVENTIONS: Immunohistochemical technique and optical microscope were adopted in the study by the author.MAIN OUTCOME MEASURES: Shapes and growth modes of neural stem cells in corpus striatum from different human fetal brains were assessed with immunohistochemical techniques.RESULTS: Neural stem cells existed in corpus striatum in different fetal age including round, oval and triangle cells. Theound and oval cells were more than triangle cells that merely presented in corpus striatum of fetal brains aged at 30 and 32 weeks. Every type of cells had big or small ones with up to three enations. Nuclei were in round and oval shapes having 1 to 4 nucleoli. Most of the cells had rarefaction chromatin and few cells had compact chromatin. Most of neural sten cells in five groups grew in a single growth mode. Neural stem cells at the age of 30 weeks were found in corpus striatum and of occasionally with symmetric cleavage growth mode. Neural stem cells at the age 28 weeks were found in corpus striatum and with symmetric cleavage and multi

  6. NOTCH Signal Regulating Role in Human Brain Glioma Stem Cells Proliferation%人脑胶质瘤干细胞增殖中NOTCH信号的调控作用

    Institute of Scientific and Technical Information of China (English)

    徐菲; 陈东; 胡继良

    2016-01-01

    目的:探讨人脑胶质瘤干细胞增殖中NOTCH信号的调控作用。方法:采用免疫磁珠法从人脑胶质瘤组织及胶质瘤细胞株中提取、分离人脑胶质瘤干细胞,对细胞进行体外培养,采用荧光定量PCR、免疫组化等方法检测相关指标,观察人脑胶质瘤干细胞增殖中NOTCH信号通路的调控作用。结果:正常脑组织的NOTCH-1蛋白累积光密度值为(294.9±29.5),低度及高度恶性胶质瘤患者的NOTCH-1蛋白累积光密度值分别为(5046.0±120.9)和(11026.2±169.1)。低度及高度恶性胶质瘤患者的NOTCH-1蛋白表达水平较正常脑组织患者明显提高,且高度恶性胶质瘤患者的NOTCH-1蛋白表达水平较低度恶性胶质瘤患者明显提高,比较差异均有统计学意义(P<0.05)。在CD133+胶质瘤细胞中,NOTCH-1、HES-1及CBF-1基因的表达水平较CD133-胶质瘤细胞明显提高,比较差异均有统计学意义(P<0.05)。结论:NOTCH-1基因在人脑胶质瘤中呈高水平表达;在人胶质瘤干细胞增殖过程中, NOTCH-1、CBF-1和HES-1等关键基因呈高表达,NOTCH信号通路在人脑胶质瘤干细胞增殖过程中起着重要调控作用,值得深入研究。%Objective:To study the NOTCH signal regulating role in human brain glioma stem cell proliferation.Method:Using magnetic beads immune method extracted from the organization for human brain glioma and glioma cell line,separated the brain glioma stem cells,cells for in vitro culture,used the fluorescent quantitative PCR and immunohistochemical method to detect the related indicators,observed the NOTCH signal pathway in the brain glioma stem cells proliferation regulation function.Result:Patients with normal brain tissue protein accumulation NOTCH-1 optical density value was (294.9±29.5),low and highly malignant gliomas NOTCH-1 protein accumulation optical density value was respectively (5046.0±120.9) and (11 026.2±169.1). Low and

  7. 神经干细胞移植治疗创伤性脑损伤的研究进展%The Research Progress of Neural Stem Cells in the Traumatic Brain Injury (TBI)

    Institute of Scientific and Technical Information of China (English)

    马明; 杨华林

    2013-01-01

    创伤性脑损伤目前仍然是全世界死亡和致残的最主要原因之一,伤后的功能恢复仍是治疗面临的难题,神经干细胞移植为促进伤后神经功能恢复带来了光明的前景。%Traumatic brain injury (TBI) represents a major cause of neurological mortality and morbidity throughout the world. After the injury the functional recovery is still the dififcult problems in treatment. Neural stem cells therapy is a burgeoning ifeld of experimental treatment that has shown promise in the management of TBI.

  8. Expression of the EGF receptor family members ErbB2, ErbB3, and ErbB4 in germinal zones of the developing brain and in neurosphere cultures containing CNS stem cells.

    Science.gov (United States)

    Kornblum, H I; Yanni, D S; Easterday, M C; Seroogy, K B

    2000-01-01

    The epidermal growth factor receptor family consists of four related tyrosine kinases: the epidermal growth factor receptor (EGF-R or ErbB), ErbB2, ErbB3, and ErbB4. These receptors are capable of extensive cross-activation upon the binding of their ligands - the EGF family of peptides for EGF-R and the neuregulins for ErbB3 and ErbB4. Since EGF-R is expressed by proliferating cells in the central nervous system (CNS), including multipotent CNS stem cells, we examined the expression of ErbB2, ErbB3 and ErbB4 in the germinal epithelia of the developing rat brain using in situ hybridization. ErbB2 and ErbB4 mRNAs were widely distributed within the germinal zones as early as E12. However, as development proceeded, ErbB2 mRNA was mainly present within the layers of cells immediately adjacent to the ventricular surface - the ventricular zone, while ErbB4 mRNA was predominantly expressed by subventricular zone cells, in the regions where these specialized germinal epithelia were present. ErbB3 mRNA distribution within germinal epithelia was more restricted, primarily confined to the diencephalon and rostral midbrain. Cultured neurospheres, which contain CNS stem cells, expressed ErbB2, ErbB4 and, to a lesser extent, ErbB3 protein as demonstrated by Western blot analysis. This expression declined during following differentiation. Heregulin-beta1, a neuregulin, had no effect on the proliferative capacity of neurospheres. Overall, our results indicate that ErbB2, ErbB3 and ErbB4 may play important and distinct roles in the genesis of the CNS. However, our in vitro data do not support a role for neuregulins in proliferation, per se, of CNS stem cells.

  9. Roles of PINK1, mTORC2, and mitochondria in preserving brain tumor-forming stem cells in a noncanonical Notch signaling pathway.

    Science.gov (United States)

    Lee, Kyu-Sun; Wu, Zhihao; Song, Yan; Mitra, Siddhartha S; Feroze, Abdullah H; Cheshier, Samuel H; Lu, Bingwei

    2013-12-15

    The self-renewal versus differentiation choice of Drosophila and mammalian neural stem cells (NSCs) requires Notch (N) signaling. How N regulates NSC behavior is not well understood. Here we show that canonical N signaling cooperates with a noncanonical N signaling pathway to mediate N-directed NSC regulation. In the noncanonical pathway, N interacts with PTEN-induced kinase 1 (PINK1) to influence mitochondrial function, activating mechanistic target of rapamycin complex 2 (mTORC2)/AKT signaling. Importantly, attenuating noncanonical N signaling preferentially impaired the maintenance of Drosophila and human cancer stem cell-like tumor-forming cells. Our results emphasize the importance of mitochondria to N and NSC biology, with important implications for diseases associated with aberrant N signaling.

  10. Neural stem cell transplantation in the hippocampus of rats with cerebral ischemia/reperfusion injury Activation of the phosphatidylinositol-3 kinase/Akt pathway and increased brain-derived neurotrophic factor expression

    Institute of Scientific and Technical Information of China (English)

    Yu Zhao; Shengtao Yao; Shijun Wang

    2010-01-01

    The phosphatidylinositol-3 kinase (PI3K)/Akt pathway and brain-derived neurotrophic factor (BDNF) are involved in neurological functional recovery following cerebral ischemia. Therefore, we hypothesized that mechanisms of neuroprotection by transplantation of neural stem cells (NSCs) on cerebral ischemia contributed to activation of the PI3K/Akt pathway and enhanced BDNF expression. In the present study, Wortmannin (a specific, covalent inhibitor of PI3K) was administered adjacent to ischemic hippocampus by stereotactic transplantation to further confirm the neuroprotective mechanisms of NSC transplantation following cerebral ischemia. Results showed that focal infarct volume was significantly smaller in the NSCs group, but the neurological behavior score in the NSC group was significantly greater than the middle cerebral artery occlusion model group, Wortmannin treatment group, and NSCs + Wortmannin treatment group. Protein expression of RDNF was significantly greater in the NSC group compared with the Wortmannin treatment group and NSCs + Wortmannin treatment group. These results suggest that the neuroprotective role of NSC transplantation in the cerebral ischemia activated the PI3K/Akt pathway and upregulated BDNF expression in lesioned brains.

  11. [Determination of brain death in organ donation: is EEG required?].

    Science.gov (United States)

    Kompanje, Erwin J O; Epker, Jelle L; de Groot, Yorick J; Wijdicks, Eelco F M; van der Jagt, Mathieu

    2013-01-01

    The determination of brain death is a prerequisite of multiple organ donation in ventilated patients in the ICU. The criteria for brain death differ internationally. In some countries, brain stem death is equivalent to brain death. In others, including the Netherlands, in addition to the determination of brain stem death, an EEG must also be carried out to rule out cortex activity according to the criteria of "whole brain death". However, this does not prove that there is complete failure of all brain functions; indeed, EEG does not examine the subcortical brain. The Dutch Health Board has established that brain death is ruled out by rest activity in the cortex, but not by persistent subcortical activity. This is conceptually incorrect. The criteria for brain stem death fit better in practice than the criteria for whole brain death. Taking an EEG should therefore no longer be an obligation in establishing brain death, as is the case in many other countries.

  12. Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior

    DEFF Research Database (Denmark)

    Baek, Jean-Ha; Schmidt, Eva; Viceconte, Nikenza

    2015-01-01

    , the HGPS mutation results in organ-specific defects. For example, bone and skin are strongly affected by HGPS, while the brain appears to be unaffected. There are no definite explanations as to the variable sensitivity to progeria disease among different organs. In addition, low levels of progerin have...

  13. What are Stem Cells?

    Directory of Open Access Journals (Sweden)

    Ahmadshah Farhat

    2014-05-01

    Full Text Available   Stem cells are undifferentiated self regenerating multi potential cells. There are three types of stem cells categories by the ability to form after cells and correlated with the body’s development process. Totipotent: these stem cells can form an entire organism such as fertilized egg. Ploripotent: ploripotent cells are those that can form any cell in the body but cannot form an entire organism such as developing embryo’s totipotent cells become ploripotent  Multipotent: Multi potent stem cells are those that can only form specific cells in the body such as blood cells based. Based on the sources of stem cells we have three types of these cells: Autologous: Sources of the patient own cells are (Autologous either the cells from patient own body or his or her cord blood. For this type of transplant the physician now usually collects the periphery rather than morrow because the procedure is easier on like a bane morrow harvest it take place outside of an operating room, and the patient does not to be under general unsetting . Allogenic: Sources of stem cells from another donore are primarily relatives (familial allogenic or completely unrelated donors. Xenogenic: In these stem cells from different species are transplanted e .g striatal porcine fetal mesan cephalic (FVM xenotransplants for Parkinson’s disease. On sites of isolation such as embryo, umbilical cord and other body tissues stem cells are named embnyonic, cord blood, and adult stem cells. The scope of results and clinical application of stem cells are such as: Neurodegenerative conditions (MS,ALS, Parkinson’s, Stroke, Ocular disorders- Glaucoma, retinitis Pigmentosa (RP, Auto Immune Conditions (Lupus, MS,R. arthritis, Diabetes, etc, Viral Conditions (Hepatitis C and AIDS, Heart Disease, Adrenal Disorders, Injury(Nerve, Brain, etc, Anti aging (hair, skin, weight control, overall well being/preventive, Emotional disorders, Organ / Tissue Cancers, Blood cancers, Blood diseases

  14. Neuroprotection of the leaf and stem of Vitis amurensis and their active compounds against ischemic brain damage in rats and excitotoxicity in cultured neurons.

    Science.gov (United States)

    Kim, Joo Youn; Jeong, Ha Yeon; Lee, Hong Kyu; Kim, SeungHwan; Hwang, Bang Yeon; Bae, KiHwan; Seong, Yeon Hee

    2012-01-15

    Vitis amurensis (Vitaceae) has been reported to have anti-oxidant and anti-inflammatory activities. The present study investigated a methanol extract from the leaf and stem of V. amurensis for neuroprotective effects on cerebral ischemic damage in rats and on excitotoxicity induced by glutamate in cultured rat cortical neurons. Transient focal cerebral ischemia was induced by 2h middle cerebral artery occlusion followed by 24h reperfusion (MCAO/reperfusion) in rats. Orally administered V. amurensis (25-100 mg/kg) reduced MCAO/reperfusion-induced infarct and edema formation, neurological deficits, and neuronal death. Depletion of glutathione (GSH) level and lipid peroxidation induced by MCAO/reperfusion was inhibited by administration of V. amurensis. The increase of phosphorylated mitogen-activated protein kinases (MAPKs), cyclooxygenase-2 (COX-2), and pro-apoptotic proteins and the decrease of anti-apoptotic protein in MCAO/reperfusion rats were significantly inhibited by treatment with V. amurensis. Exposure of cultured cortical neurons to 500 μM glutamate for 12h induced neuronal cell death. V. amurensis (1-50 μg/ml) and (+)-ampelopsin A, γ-2-viniferin, and trans-ε-viniferin isolated from the leaf and stem of V. amurensis inhibited glutamate-induced neuronal death, the elevation of intracellular calcium ([Ca(2+)](i)), the generation of reactive oxygen species (ROS), and changes of apoptosis-related proteins in cultured cortical neurons, suggesting that the neuroprotective effect of V. amurensis may be partially attributed to these compounds. These results suggest that the neuroprotective effect of V. amurensis against focal cerebral ischemic injury might be due to its anti-apoptotic effect, resulting from anti-excitotoxic, anti-oxidative, and anti-inflammatory effects and that the leaf and stem of V. amurensis have possible therapeutic roles for preventing neurodegeneration in stroke.

  15. Stem cells as promising therapeutic options for neurological disorders.

    Science.gov (United States)

    Yoo, Jongman; Kim, Han-Soo; Hwang, Dong-Youn

    2013-04-01

    Due to the limitations of pharmacological and other current therapeutic strategies, stem cell therapies have emerged as promising options for treating many incurable neurologic diseases. A variety of stem cells including pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells) and multipotent adult stem cells (i.e., fetal brain tissue, neural stem cells, and mesenchymal stem cells from various sources) have been explored as therapeutic options for treating many neurologic diseases, and it is becoming obvious that each type of stem cell has pros and cons as a source for cell therapy. Wise selection of stem cells with regard to the nature and status of neurologic dysfunctions is required to achieve optimal therapeutic efficacy. To this aim, the stem cell-mediated therapeutic efforts on four major neurological diseases, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke, will be introduced, and current problems and future directions will be discussed.

  16. Advances in stem cell research

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@In 1998, biologists Thomson and Gearhart successfully derived stem cells from human embryos. One year later, several researchers discovered that adult stem cells still retain the ability to be differentiated into unrelated types of cells. Advances in stem cell research open a promising direction for applied medical science. Moreover, it may also force scientists to reconsider the fundamental theory about how cells grow up. Stem cell research was considered by Science as the top of the ten breakthroughs of science of the year[1]. This paper gives a survey of recent advances in stem cell research. 1 Overview In the 1980s, embryonic stem cell and/or embryonic germ cell line (ES cell line, EG cell line) of multifarious mammalian animals, especially those of non-human pri-mates, had been established. In 1998, Thomson and Shamblott obtained ES, EG cell lines from human blasto-cysts and gonad ridges of early human embryos, respec-tively. Their research brought up an ethical debate about whether human embryos can be used as experimental materials. It was not appeased until 1999 when research-ers discovered that stem cells from adults still retain the ability to become different kinds of tissue cells. For in-stance, brain cells can become blood cells[2], and cells from bone marrow can become cells in liver. Scientists believe, for a long time, that cells can only be developed from early pluripotent embryo cells; the differentiation potential of stem cells from mature tissues is restricted to only one of the cell types of the tissue where stem cells are obtained. Recent stem cell researches, however, sub-verted the traditional view of stem cells. These discoveries made scientists speed ahead with the work on adult stem cells, hoping to discover whether their promise will rival that of ES cells.

  17. Stem Cells

    Directory of Open Access Journals (Sweden)

    Madhukar Thakur

    2015-02-01

    Full Text Available Objective: The objective of this presentation is to create awareness of stem cell applications in the ISORBE community and to foster a strategy of how the ISORBE community can disseminate information and promote the use of radiolabeled stem cells in biomedical applications. Methods: The continued excitement in Stem Cells, in many branches of basic and applied biomedical science, stems from the remarkable ability of stem cells to divide and develop into different types of cells in the body. Often called as Magic Seeds, stem cells are produced in bone marrow and circulate in blood, albeit at a relatively low concentration. These virtues together with the ability of stem cells to grow in tissue culture have paved the way for their applications to generate new and healthy tissues and to replace diseased or injured human organs. Although possibilities of stem cell applications are many, much remains yet to be understood of these remarkable magic seeds. Conclusion: This presentation shall briefly cover the origin of stem cells, the pros and cons of their growth and division, their potential application, and shall outline some examples of the contributions of radiolabeled stem cells, in this rapidly growing branch of biomedical science

  18. Stem cells in the nervous system.

    Science.gov (United States)

    Maldonado-Soto, Angel R; Oakley, Derek H; Wichterle, Hynek; Stein, Joel; Doetsch, Fiona K; Henderson, Christopher E

    2014-11-01

    Given their capacity to regenerate cells lost through injury or disease, stem cells offer new vistas into possible treatments for degenerative diseases and their underlying causes. As such, stem cell biology is emerging as a driving force behind many studies in regenerative medicine. This review focuses on the current understanding of the applications of stem cells in treating ailments of the human brain, with an emphasis on neurodegenerative diseases. Two types of neural stem cells are discussed: endogenous neural stem cells residing within the adult brain and pluripotent stem cells capable of forming neural cells in culture. Endogenous neural stem cells give rise to neurons throughout life, but they are restricted to specialized regions in the brain. Elucidating the molecular mechanisms regulating these cells is key in determining their therapeutic potential as well as finding mechanisms to activate dormant stem cells outside these specialized microdomains. In parallel, patient-derived stem cells can be used to generate neural cells in culture, providing new tools for disease modeling, drug testing, and cell-based therapies. Turning these technologies into viable treatments will require the integration of basic science with clinical skills in rehabilitation.

  19. Two Domains of Vimentin Are Expressed on the Surface of Lymph Node, Bone and Brain Metastatic Prostate Cancer Lines along with the Putative Stem Cell Marker Proteins CD44 and CD133

    Energy Technology Data Exchange (ETDEWEB)

    Steinmetz, Nicole F. [Case Western Reserve University, Department of Biomedical Engineering, 10900 Euclid Ave, Cleveland, OH 44106 (United States); Maurer, Jochen [Sanford-Burnham, Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037 (United States); Sheng, Huiming [Torrey Pines Institute for Molecular Studies, Division of Immune Regulation, 3550 General Atomics Court, San Diego, CA 92121 (United States); Bensussan, Armand [INSERM U976, Hôpital Saint Louis, F-75475 Paris (France); Department of Immunology, Dermatology and Oncology, Univ Paris Diderot, Sorbonne Paris Cité, UMRS976 F-75475 Paris (France); Maricic, Igor; Kumar, Vipin [Torrey Pines Institute for Molecular Studies, Laboratory of Autoimmunity, 3550 General Atomics Court, San Diego, CA 92121 (United States); Braciak, Todd A., E-mail: tbraciak@tpims.org [Torrey Pines Institute for Molecular Studies, Division of Immune Regulation, 3550 General Atomics Court, San Diego, CA 92121 (United States)

    2011-07-13

    Vimentin was originally identified as an intermediate filament protein present only as an intracellular component in many cell types. However, this protein has now been detected on the surface of a number of different cancer cell types in a punctate distribution pattern. Increased vimentin expression has been indicated as an important step in epithelial-mesenchymal transition (EMT) required for the metastasis of prostate cancer. Here, using two vimentin-specific monoclonal antibodies (SC5 and V9 directed against the coil one rod domain and the C-terminus of the vimentin protein, respectively), we examined whether either of these domains would be displayed on the surface of three commonly studied prostate cancer cell lines isolated from different sites of metastases. Confocal analysis of LNCaP, PC3 and DU145 prostate cancer cell lines (derived from lymph node, bone or brain prostate metastases, respectively) demonstrated that both domains of vimentin are present on the surface of these metastatic cancer cell types. In addition, flow cytometric analysis revealed that vimentin expression was readily detected along with CD44 expression but only a small subpopulation of prostate cancer cells expressed vimentin and the putative stem cell marker CD133 along with CD44. Finally, Cowpea mosaic virus (CPMV) nanoparticles that target vimentin could bind and internalize into tested prostate cancer cell lines. These results demonstrate that at least two domains of vimentin are present on the surface of metastatic prostate cancer cells and suggest that vimentin could provide a useful target for nanoparticle- or antibody- cancer therapeutic agents directed against highly invasive cancer and/or stem cells.

  20. Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior

    DEFF Research Database (Denmark)

    Baek, Jean-Ha; Schmidt, Eva; Viceconte, Nikenza;

    2015-01-01

    Hutchinson–Gilford progeria syndrome (HGPS) is a segmental progeroid syndrome with multiple features suggestive of premature accelerated aging. Accumulation of progerin is thought to underlie the pathophysiology of HGPS. However, despite ubiquitous expression of lamin A in all differentiated cells......, the HGPS mutation results in organ-specific defects. For example, bone and skin are strongly affected by HGPS, while the brain appears to be unaffected. There are no definite explanations as to the variable sensitivity to progeria disease among different organs. In addition, low levels of progerin have...

  1. M-CSF deficiency leads to reduced metallothioneins I and II expression and increased tissue damage in the brain stem after 6-aminonicotinamide treatment

    DEFF Research Database (Denmark)

    Penkowa, Milena; Poulsen, Christian; Carrasco, Javier

    2002-01-01

    -CSF in neurodegeneration and brain cell death, we have examined the effect of 6-AN on osteopetrotic mice with genetic M-CSF deficiency (op/op mice). The 6-AN-induced degeneration of gray-matter areas was comparable in control and op/op mice, but the numbers of reactive astrocytes, macrophages, and lymphocytes...... in the damaged areas were significantly decreased in op/op mice relative to controls. The levels of oxidative stress (as determined by using immunoreactivity for inducible nitric oxide synthase, nitrotyrosine, and malondialdehyde) and apoptotic cell death (as determined by using TUNEL and immunoreactivity...

  2. 脑创伤程度对大鼠伤后胚胎神经干细胞移植的影响%Impact of injury severity on transplantation of embryonic neural stem cells following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    洪军; 崔建忠; 黎洁; 刘兴宇; 周云涛

    2011-01-01

    Objective To explore the influence of injury severity on transplantation of embryonic neural stem cells (NSCs) after traumatic brain injury (TBI).Methods The NSCs were isolated from the hippocampus of fetal rats aged at from 12-14 days.The cells were cultured and proliferated in the serum-free medium and identified in vitro.The animals received transplants in the bilateral hippocampal areas at day 3 following mild or moderate TBI separately.Conventional histology,TUNEL and immunohistology were examined to detect BrdU,NSE,GFAP,GalC,NGF and BDNF at day 14 post-implantation.Results BrdU-labeled positive cells in the bilateral hippocampus in the mild TBI group were more than those in the moderate TBI group at day 14 post-implantation.Significant differentiation of the astrocytes recognized as GFAP positive cells in the bilateral hippocampus was found at day 14 post-implantation.The expression of NGF and BDNF proteins was increased following TBI,the most evident in the mild TBI group.Conclusion The influence of injury severity on transplantation may be associated with the change of the microenvironment after TBI.%目的 探讨不同程度创伤性脑损伤(traumatic brain injury,TBI)对伤后胚胎神经干细胞(neural stem cells,NSCs)移植的影响. 方法 从孕12~ 14 d胚胎大鼠海马组织中分离NSCs,采用无血清培养法,进行体外培养、扩增和鉴定.大鼠分别于轻型、中型TBI后3d行胚胎NSCs双侧海马区移植;细胞移植14 d后行组织学和TUNEL检测,并对BrdU、NSE、GFAP、GalC、NGF、BDNF蛋白行免疫组化检测. 结果 移植治疗后14 d,轻型TBI组双侧海马区Brdu阳性细胞数明显多于中型TBI组.移植胚胎NSCs脑内分化以GFAP阳性胶质细胞为主.轻、中型TBI后NGF和BDNF蛋白阳性表达增加,其中以轻型TBI组表达最为显著. 结论 轻型和中型TBI对NSCs移植的影响与伤后脑组织局部微环境因素的改变密切相关.

  3. The Comparative Study on the Proliferation and Differentiation of Neural Stem Cells from the Gut and Brain of Rats%肠与脑来源神经干细胞的增殖和分化特性比较

    Institute of Scientific and Technical Information of China (English)

    王永飚; 朱利斌; 刘征吉; 夏立广; 李仲荣

    2011-01-01

    目的 探索肠神经干细胞(ENSCs)的增殖和分化特性,寻找神经干细胞移植治疗肠道神经元缺陷性疾病的合适干细胞源.方法 采用神经干细胞培养和分离技术,对来自同一大鼠肠道及大脑的神经干细胞(CNS-NSCs)进行体外培养,通过神经球生长直接观察法、CCK-8细胞增殖测定法、流式细胞仪测定,比较研究两者的生长和增殖情况及成熟分化特性.结果 与CNS-NSCs相比,ENSCs神经球增殖速度较慢;ENSCs神经球表面常有长突起,并相互连接成网络状,显示早期成熟分化的迹象;CCK-8法测得ENSCs的吸光度明显低于CNS-NSCs(P0.05)、GFAP阳性细胞比例分别为21.7%和22.5%(P>0.05)、Nestin阳性细胞比例分别为10.8%和10.8%(P>0.05). 结论 ENSCs与CNS-NSCs具有类似的增殖、分化特性,但ENSCs增殖速度较慢,易于成熟分化.%Objective To explore the characteristics of proliferation and differentiation of enteric neural stem cells ( ENSCs ), and look for the suitable source of neural stem cells for transplantation treatment of developmental defects of enteric neuron. Methods We used the culture medium and isolation technique adopted in our laboratory to culture in vitro enteric neural stem cells ( ENSCs ) from gut and central nervous system - derived neural stem cells( CNS - NSCs ) from brain obtained from the same embryonic rat. The state of growth, the characteristics of proliferation and differentiation of hoth neural stem cells were compared by direct observation of neurosphere growth, CCK - 8 method and flow cytometry. Results Compared to the CNS - NSCs, the proliferation of ENSCs neurosphere was much slower. Some long dendrites often grew from the surface of the ENSCs neurosphere, and connected each other and formed a network,which seemed to differentiation in early stage. The growth rate of the ENSCs was much lower than that of CNS - NSCs( P <0. 05 ) by CCK -8 method. The percentage of TUJ -1 positive cells of ENSCs and CNS

  4. 经鼻内途径移植骨髓间充质干细胞治疗脑损伤:还有多少问题待验证?%Intranasal delivery of bone marrow mesenchymal stem cells for brain injuries:how many questions to be verified?

    Institute of Scientific and Technical Information of China (English)

    阎雪晶; 王欣玲; 杨咪咪; 侯伟健

    2014-01-01

    BACKGROUND:Transplantation of bone marrow mesenchymal stem cells can promote repair of brain injuries in animals. OBJECTIVE:To summarize the research progress in intranasal delivery of bone marrow mesenchymal stem cells to the brain. METHODS:A computer-based online retrieval of PubMed and Wanfang databases was performed to search papers published during January 1999 to January 2014 with the key words of“bone marrow mesenchymal stem cells, brain injury, transplantation”in English and Chinese. Thirty-eight papers were included in the final analysis. RESULTS AND CONCLUSION:Nowadays, many studies have been certified that the transplantation of bone marrow mesenchymal stem cells can significantly ameliorate the function of cranial nerve in animal models of brain injury. Many researchers have searched for the transplantation methods and approaches and have made progresses in many aspects. In this article, we compare the different transplantation ways of bone marrow mesenchymal stem cells to the brain. We focus on the intranasal transplantation route in the fol owing aspects:processing of the nasal mucosa;delivery route to the brain;labeling and intracranial observation of stem cells;animal experiments. We conclude that the intranasal delivery of bone marrow mesenchymal stem cells to the brain has a wide clinical application as a noninvasive transplantation.%背景:动物实验发现骨髓间充质干细胞移植后可促进脑损伤的修复。目的:综述经鼻内途径移植骨髓间充质干细胞到颅内的现状。方法:应用计算机检索1999年1月至2014年1月PubMed相关文章,检索词为“bone marrow mesenchymal stem cel ,brain injury,transplantation”,并限定文章语言种类为English。同时计算机检索1999年1月至2014年1月万方数据库相关文章,检索词为“骨髓间充质干细胞、脑损伤、移植”,并限定文章语言种类为中文,最终纳入符合标准的文献38篇。结果与结论:近年

  5. Stem Cells

    DEFF Research Database (Denmark)

    Sommerlund, Julie

    2004-01-01

    '. This paper is about tech-noscience, and about the proliferation of connections and interdependencies created by it.More specifically, the paper is about stem cells. Biotechnology in general has the power to capture the imagination. Within the field of biotechnology nothing seems more provocative...... and tantalizing than stem cells, in research, in medicine, or as products....

  6. Generalized Potential of Adult Neural Stem Cells

    Science.gov (United States)

    Clarke, Diana L.; Johansson, Clas B.; Wilbertz, Johannes; Veress, Biborka; Nilsson, Erik; Karlström, Helena; Lendahl, Urban; Frisén, Jonas

    2000-06-01

    The differentiation potential of stem cells in tissues of the adult has been thought to be limited to cell lineages present in the organ from which they were derived, but there is evidence that some stem cells may have a broader differentiation repertoire. We show here that neural stem cells from the adult mouse brain can contribute to the formation of chimeric chick and mouse embryos and give rise to cells of all germ layers. This demonstrates that an adult neural stem cell has a very broad developmental capacity and may potentially be used to generate a variety of cell types for transplantation in different diseases.

  7. Learn About Stem Cells

    Science.gov (United States)

    ... Patient Handbook Stem Cell Glossary Search Toggle Nav Stem Cell Basics Stem cells are the foundation from which ... original cell’s DNA, cytoplasm and cell membrane. About stem cells Stem cells are the foundation of development in ...

  8. 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.

  9. Brain Basics

    Medline Plus

    Full Text Available ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  10. Brain Basics

    Science.gov (United States)

    ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  11. Neural stem cells could serve as a therapeutic material for age-related neurodegenerative diseases.

    Science.gov (United States)

    Suksuphew, Sarawut; Noisa, Parinya

    2015-03-26

    Progressively loss of neural and glial cells is the key event that leads to nervous system dysfunctions and diseases. Several neurodegenerative diseases, for instance Alzheimer's disease, Parkinson's disease, and Huntington's disease, are associated to aging and suggested to be a consequence of deficiency of neural stem cell pool in the affected brain regions. Endogenous neural stem cells exist throughout life and are found in specific niches of human brain. These neural stem cells are responsible for the regeneration of new neurons to restore, in the normal circumstance, the functions of the brain. Endogenous neural stem cells can be isolated, propagated, and, notably, differentiated to most cell types of the brain. On the other hand, other types of stem cells, such as mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells can also serve as a source for neural stem cell production, that hold a great promise for regeneration of the brain. The replacement of neural stem cells, either endogenous or stem cell-derived neural stem cells, into impaired brain is highly expected as a possible therapeutic mean for neurodegenerative diseases. In this review, clinical features and current routinely treatments of age-related neurodegenerative diseases are documented. Noteworthy, we presented the promising evidence of neural stem cells and their derivatives in curing such diseases, together with the remaining challenges to achieve the best outcome for patients.

  12. MeCP2 regulates the synaptic expression of a Dysbindin-BLOC-1 network component in mouse brain and human induced pluripotent stem cell-derived neurons.

    Directory of Open Access Journals (Sweden)

    Jennifer Larimore

    Full Text Available Clinical, epidemiological, and genetic evidence suggest overlapping pathogenic mechanisms between autism spectrum disorder (ASD and schizophrenia. We tested this hypothesis by asking if mutations in the ASD gene MECP2 which cause Rett syndrome affect the expression of genes encoding the schizophrenia risk factor dysbindin, a subunit of the biogenesis of lysosome-related organelles complex-1 (BLOC-1, and associated interacting proteins. We measured mRNA and protein levels of key components of a dysbindin interaction network by, quantitative real time PCR and quantitative immunohistochemistry in hippocampal samples of wild-type and Mecp2 mutant mice. In addition, we confirmed results by performing immunohistochemistry of normal human hippocampus and quantitative qRT-PCR of human inducible pluripotent stem cells (iPSCs-derived human neurons from Rett syndrome patients. We defined the distribution of the BLOC-1 subunit pallidin in human and mouse hippocampus and contrasted this distribution with that of symptomatic Mecp2 mutant mice. Neurons from mutant mice and Rett syndrome patients displayed selectively reduced levels of pallidin transcript. Pallidin immunoreactivity decreased in the hippocampus of symptomatic Mecp2 mutant mice, a feature most prominent at asymmetric synapses as determined by immunoelectron microcopy. Pallidin immunoreactivity decreased concomitantly with reduced BDNF content in the hippocampus of Mecp2 mice. Similarly, BDNF content was reduced in the hippocampus of BLOC-1 deficient mice suggesting that genetic defects in BLOC-1 are upstream of the BDNF phenotype in Mecp2 deficient mice. Our results demonstrate that the ASD-related gene Mecp2 regulates the expression of components belonging to the dysbindin interactome and these molecular differences may contribute to synaptic phenotypes that characterize Mecp2 deficiencies and ASD.

  13. Neural stem cells intravenous implantation improves the neurological function of mice after traumatic brain injury%神经干细胞移植显著改善脑外伤小鼠的神经功能

    Institute of Scientific and Technical Information of China (English)

    仇波; 王勇; 吴鹏飞; 秦晓飞; 王运杰

    2012-01-01

    目的 探讨鼠源性神经干细胞( neural stem cells,NSCs)静脉移植对脑外伤小鼠海马的治疗作用.方法 30只BALB/c小鼠随机分为3组,假手术组(10只)、脑外伤组(10只)和NSCs移植组(10只).NSCs移植7d后,根据小鼠脑损伤NSS(Neurological Severity Score)评分系统进行评分.TUNEL法检测各组小鼠海马细胞凋亡情况.免疫组化和Western blot检测各组小鼠海马半胱氨酸蛋白酶-3(cysteinyl aspirate specificproteinase3,caspase-3)蛋白的表达.结果 NSCs移植7d后,NSS评分显示NSCs移植组的神经功能明显改善(P<0.001).TUNEL法检测结果发现,脑外伤组小鼠海马凋亡细胞百分数明显高于假手术组(P<0.05),但经过NSCs移植后,凋亡率显著下降.免疫组化和Western blot结果显示,脑外伤组小鼠海马caspase-3蛋白表达量明显高于假手术组(P<0.05),但NSCs移植组小鼠海马caspase-3表达明显降低(P<0.05).结论 静脉NSCs移植能够显著改善脑外伤小鼠的神经功能,其机制可能与降低caspase-3的表达有关.%Objective To study the effect of neural stem cells(NSCs)intravenous implantation on neurological function of mice after traumatic brain injury. Methods 30 BALB/c mice were randomly divided into the sham group(10, S group), traumatic brain injury group(10, T group)and NSCs implantation group (10, N group). The neurufuiiclion of mice was scored by NSS scoring system. The apoptotic hippocampus cells of all groups were stained using TUNEL assay, and expression levels of caspase-3 in hippocampus of all groups were examined by immunohistochemistry and Western blot. Results After NSCs implantation, neurological function of N group mice evaluated by Neurological Severity Score(NSS)was significantly improved compared to T group (P<0.00l). The percentages of apoptotic hippocampal cells increased significantly in T group compared to S group, and decreased after NSCs implantation (P<0.05). The expression levels of caspase-3 in hippocampus

  14. U251胶质瘤细胞系中脑肿瘤干细胞的分离、培养及鉴定%Isolation,Culture and Identification of Brain Tumor Stem Cellswithin U251 Glioma Cell Line In Vitro

    Institute of Scientific and Technical Information of China (English)

    陈成; 芦明; 李茗初; 方加胜

    2012-01-01

      Objective This study was to isolate, culture and identificate brain tumor stem cel s from U251 Gliome cel line in vitro and observe their growth pattern.To establish a fundation for further reseach of brain tumor stem cel . Methods U251cel s were seeded in serum-free DMEM-F12 medium supplemented with B27, EGF and bFGF in 6-wel plates, after U251 brain tumor spheres formed, they were dissociated and passaged in fresh medium periodical y. U251 brain tumor spheres and the single cel s of them were induced to differentiate in the medium with 10%FBS supplemented. U251cel s cultivate in serum-supplemented medium and serum-free medium alternately. At last we performed immunocytochemistry of U251 brain tumor spheres for CD133 and Nestin. Results Some U251 glioma cel have the capacity to self-renew, proliferate and generate free-floating neurosphere-like brain tumor spheres in serum-free medium in vitro. U251 glioma spheres and the single cel s of them can be induced to differentiate and adherent to the bottom of the culture plates. The growing patterns of U251 glioma cel line can be converted by changing the culture mediums. The brain tumor stem cel are CD133+Nestin+cel s. Conclusion The U251 glioma cel line contain brain tumor stem cel s which can be isolated, proliferated and differentiated in vitro. The research of brain tumor stem cel s may provide a new platform for brain tumor study.%  目的本研究旨在从U251胶质瘤细胞系中分离、培养和鉴定脑肿瘤干细胞,观察其的生长特征,为脑肿瘤干细胞的进一步研究打下基础。方法应用简化的无血清培养基和悬浮培养法培养U251细胞,并将获得的脑肿瘤干细胞接种于含血清培养基中观察其分化;交替用含血清培基和无血清培基培养U251细胞,观察其生长特性;用免疫荧光法检测脑肿瘤干细胞中CD133和Nestin的表达。结果 U251细胞接种至无血清培养基后,部分细胞能够存活并增殖为悬浮

  15. Brain herniation

    Science.gov (United States)

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

  16. The diagnosis of brain death

    Directory of Open Access Journals (Sweden)

    Goila Ajay

    2009-01-01

    Full Text Available Physicians, health care workers, members of the clergy, and laypeople throughout the world have accepted fully that a person is dead when his or her brain is dead. Although the widespread use of mechanical ventilators and other advanced critical care services have transformed the course of terminal neurologic disorders. Vital functions can now be maintained artificially for a long period of time after the brain has ceased to function. There is a need to diagnose brain death with utmost accuracy and urgency because of an increased awareness amongst the masses for an early diagnosis of brain death and the requirements of organ retrieval for transplantation. Physicians need not be, or consult with, a neurologist or neurosurgeon in order to determine brain death. The purpose of this review article is to provide health care providers in India with requirements for determining brain death, increase knowledge amongst health care practitioners about the clinical evaluation of brain death, and reduce the potential for variations in brain death determination policies and practices amongst facilities and practitioners. Process for brain death certification has been discussed under the following: 1. Identification of history or physical examination findings that provide a clear etiology of brain dysfunction. 2. Exclusion of any condition that might confound the subsequent examination of cortical or brain stem function. 3. Performance of a complete neurological examination including the standard apnea test and 10 minute apnea test. 4. Assessment of brainstem reflexes. 5. Clinical observations compatible with the diagnosis of brain death. 6. Responsibilities of physicians. 7. Notify next of kin. 8. Interval observation period. 9. Repeat clinical assessment of brain stem reflexes. 10. Confirmatory testing as indicated. 11. Certification and brain death documentation.

  17. 小剂量尿激酶联合胞磷胆碱钠治疗脑干梗死的疗效观察%Effect of low dose urokinase and citicolin in treating brain stem infarction

    Institute of Scientific and Technical Information of China (English)

    张守娟; 韩延昭; 李绵; 毕青松

    2015-01-01

    目的:探讨小剂量尿激酶联合胞磷胆碱钠治疗脑干梗死的疗效。方法选取2010年1月—2013年6月于乐亭县中医医院神经内科住院的急性脑干梗死患者30例,结合患者及家属意愿将患者分为治疗组与对照组,各15例。治疗组予以尿激酶联合胞磷胆碱钠治疗治疗,对照组予以奥扎格雷钠治疗。观察两组患者脑卒中临床神经功能缺损程度评分( NIHSS)、临床疗效及不良反应发生情况。结果治疗前两组患者NIHSS评分比较,差异无统计学意义(P>0.05),治疗后24h、14d治疗组患者NIHSS评分低于对照组,差异有统计学意义(P0. 05),24 hours after treatment and 14 days after treatment,NIHSS scores of the treatment group was lower than that of control group(P<0. 05);the total effective rate of treatment group was higher than that of control group(P<0. 05);no one of the two groups occurred serious adverse reactions. Conclusion Low dose urokinase and citicolin has notable curative effect in the treatment of brain stem infarction,can improve the prognosis of patients and is with less adverse reactions.

  18. 脑创伤骨髓间充质干细胞修复及MR活体示踪的研究进展%Progress of traumatic brain injury treated by bone marrow-derived mesenchymal stem cells and its magnetic resonance imaging tracing in vivo

    Institute of Scientific and Technical Information of China (English)

    彭德新

    2011-01-01

    Traumatic brain injury ( TBI) is comnmn and acute , with severe injury and poor prognosis. Bone marrow-derived mesenchymal stem cells (BMSCs) are non-hematopoietic adult stem cells. BMSCs are widely available, easy to cultivate, potent to multi-differentiate, and regarded as the best seed cells in transplantation. BMSCs have been applied to research on therapy. This paper reviews the progress on the treatment of TBI by BMSCs and its MRI tracing in vivo.%脑创伤(traumatic brain injury,TBI)是常见的急重症,其损伤严重、预后差.骨髓间充质干细胞(bone marrow mesenchymal stem cells BMSC)是一种非造血系统的成体干细胞,具有来源广泛、易于培养、多向分化的生物学特性,是细胞移植的首选种子细胞.目前,BMSC已进入临床疾病治疗的研究.文中就BMSC治疗TBI及其MR活体示踪进展作一综述.

  19. Hippocampal stem cells: so they are multipotent!

    Institute of Scientific and Technical Information of China (English)

    Verdon Taylor

    2011-01-01

    Although neurogenesis continues throughout life in the mammalian brain, the issue of whether the stem cells that drive the process in vivo are self-renewing and multipotent remains unclear. In a recent landmark paper by Bonaguidi et al. (2011) published in Cell, the authors provide clonal evidence that neural stem cells in the dentate gyrus of the adult hippocampus are indeed multipotent and undergo symmetric cell divisions.%Although neurogenesis continues throughout life in the mammalian brain,the issue of whether the stem cells that drive the process in vivo are self-renewing and multipotent remains unclear.In a recent landmark paper by Bonaguidi et al.(2011) pubiished in Cell,the authors provide cional evidence that neural stem cells in the dentate gyrus of the adult hippocampus are indeed multipotent and undergo symmetric cell divisions.

  20. Stem Cell Basics

    Science.gov (United States)

    ... Tips Info Center Research Topics Federal Policy Glossary Stem Cell Information General Information Clinical Trials Funding Information Current ... Basics » Stem Cell Basics I. Back to top Stem Cell Basics I. Introduction: What are stem cells, and ...

  1. Cortical network from human embryonic stem cells

    OpenAIRE

    2010-01-01

    Abstract The connection of embryonic stem cell technology and developmental biology provides valuable tools to decipher the mechanisms underlying human brain development and diseases, especially among neuronal populations, that are not readily available in primary cultures. It is obviously the case of neurons forming the human cerebral cortex. In the images that are presented, the neurons were generated in vitro from human embryonic stem cells via forebrain-like progenitors. Maintained in cul...

  2. Invitro differentiation of embryonic neural stem cells from rabbit retina and brain%体外培养及诱导胚兔视网膜及脑神经干细胞分化的研究

    Institute of Scientific and Technical Information of China (English)

    吴婵; 董方田; 陈连凤; 许卓再

    2009-01-01

    Objective To isolate neural stem cells (NSCs) from rabbit retina and brain,and induce differentiation of those NSCs using different culture media.Methods Single-cell suspensions of retina and cerebral cortex were prepared from rabbit embryo,cultured in 5 types of different media to isolate the NSCs by continual passages.After 3 passages,NSCs were induced to differentiation in 2 types of different media for 8 to 10 days.NSCs and induced-retinal ceils were examined by immunofluorescence and flow cytometry for the expression pattern of some specific antigens.Results Immunofluorescence showed that NSCs from retina and brain,cultured in serum-free media,both expressed Nestin partially.Flow cytometry showed that Nestin positive cells were significantly decreased while the Rhodopsin and Thy1.1 positive cells were increased after induction.Compared with the combined induction of all-trans retinoid acid (ATRA) and serum,5 % FBS (fetal bovine serum) led to higher expression of Rhodopsin (P<0.01),but lower expression of Thy1.1 (P=0.01).Conclusion Serum-free media with N2,EGF,bFGF,LIF is the best for NSCs purification.Both induciton media can induce NSCs to differentiate.Retina NSCs have higher potentials to differentiate into retinal neuro-epithelial cells than brain NSCs.%目的 比较体外不同培养条件对视网膜及脑神经干细胞(NSCs)视紫红质的纯化能力及不同诱导条件对NSCs的诱导分化能力.方法 取胚兔视网膜及大脑皮质制备单细胞悬液,分别在5种不同培养基中进行体外培养并纯化.选取无血清条件下传3代的NSCs,分别在2种培养基中诱导8~10 d.采用免疫荧光法及流式细胞仪检测所获得细胞的神经干细胞和视网膜神经上皮细胞抗原的表达.结果 免疫荧光法显示无血清培养条件下2种组织来源的NSCs均部分表达巢蛋白.流式细胞术显示2种诱导方式均部分细胞表达巢蛋白,较诱导前明显降低,而视紫红质及Thy1.1的表达

  3. Stem cells.

    Science.gov (United States)

    Redi, Carlo Alberto; Monti, Manuela; Merico, Valeria; Neri, Tui; Zanoni, Mario; Zuccotti, Maurizio; Garagna, Silvia

    2007-01-01

    The application of stem cells to regenerative medicine is one of the actual hot topics in biomedicine. This research could help the cure of a number of diseases that are affecting a large share of the population. Some good results in cell replacement have already been obtained (infarcted heart, diabetes, Parkinson disease), apart from those of more traditional applications like severe burns and blood tumors. We are now facing crucial questions in stem cell biology. One of the key questions is how a cell begins to proliferate or differentiate. Genome reprogramming, both following nuclear transfer and cytoplast action, will likely highlight some of the molecular mechanisms of cell differentiation and dedifferentiation. In turn, these clues should be useful to the production of populations of reprogrammed cells that could develop into tissues or, in the future, into proper organs. We will overview what stem cells are, what roles they play in normal developmental processes and how stem cells could have the potential to treat diseases.

  4. Why STEM?

    Science.gov (United States)

    Mitts, Charles R.

    2016-01-01

    The International Technology and Engineering Educators Association (ITEEA) defines STEM as a new transdisciplinary subject in schools that integrates the disciplines of science, technology, engineering, and mathematics into a single course of study. There are three major problems with this definition: There is no consensus in support of the ITEEA…

  5. Adult neural stem cells-Functional potential and therapeutic applications

    Institute of Scientific and Technical Information of China (English)

    YANG Lin; ZHU Jianhong

    2004-01-01

    The adult brain has been thought traditionally as a structure with a very limited regenerative capacity. It is now evident that neurogenesis in adult mammalian brain is a prevailing phenomenon. Neural stem cells with the ability to self-renew, differentiate into neurons, astrocytes and oligodendrocytes reside in some regions of the adult brain. Adult neurogenesis can be stimulated by many physiological factors including pregnancy. More strikingly, newborn neurons in hippocampus integrally function with local neurons, thus neural stem cells might play important roles in memory and learning function. It seems that neural stem cells could transdifferentiate into other tissues, such as blood cells and muscles. Although there are some impediments in this field, some attempts have been made to employ adult neural stem cells in the cell replacement therapy for traumatic and ischemic brain injuries.

  6. Stem cells in neurology - current perspectives

    Directory of Open Access Journals (Sweden)

    Chary Ely Marquez Batista

    2014-06-01

    Full Text Available Central nervous system (CNS restoration is an important clinical challenge and stem cell transplantation has been considered a promising therapeutic option for many neurological diseases. Objective : The present review aims to briefly describe stem cell biology, as well as to outline the clinical application of stem cells in the treatment of diseases of the CNS. Method : Literature review of animal and human clinical experimental trials, using the following key words: “stem cell”, “neurogenesis”, “Parkinson”, “Huntington”, “amyotrophic lateral sclerosis”, “traumatic brain injury”, “spinal cord injury”, “ischemic stroke”, and “demyelinating diseases”. Conclusion : Major recent advances in stem cell research have brought us several steps closer to their effective clinical application, which aims to develop efficient ways of regenerating the damaged CNS.

  7. Zika virus impairs growth in human neurospheres and brain organoids.

    Science.gov (United States)

    Garcez, Patricia P; Loiola, Erick Correia; Madeiro da Costa, Rodrigo; Higa, Luiza M; Trindade, Pablo; Delvecchio, Rodrigo; Nascimento, Juliana Minardi; Brindeiro, Rodrigo; Tanuri, Amilcar; Rehen, Stevens K

    2016-05-13

    Since the emergence of Zika virus (ZIKV), reports of microcephaly have increased considerably in Brazil; however, causality between the viral epidemic and malformations in fetal brains needs further confirmation. We examined the effects of ZIKV infection in human neural stem cells growing as neurospheres and brain organoids. Using immunocytochemistry and electron microscopy, we showed that ZIKV targets human brain cells, reducing their viability and growth as neurospheres and brain organoids. These results suggest that ZIKV abrogates neurogenesis during human brain development.

  8. Brain Basics

    Medline Plus

    Full Text Available ... Basics will introduce you to some of this science, such as: How the brain develops How genes and the environment affect the brain The basic structure of the brain How different parts of the brain communicate and work with each other How changes in the brain ...

  9. Brain Fingerprinting

    Directory of Open Access Journals (Sweden)

    Ravi Kumar

    2012-12-01

    Full Text Available Brain Fingerprinting is a scientific technique to determine whether or not specific information is stored in an individual's brain by measuring a electrical brain wave response to Word, phrases, or picture that are presented on computer screen. Brain Fingerprinting is a controversial forensic science technique that uses electroencephalography (EEG to determine whether specific information is stored in a subject's brain.

  10. Brain Fingerprinting

    Directory of Open Access Journals (Sweden)

    ravi kumar

    2012-12-01

    Full Text Available Brain Fingerprinting is a scientific technique to determine whether or not specific information is stored in an individual's brain by measuring a electrical brain wave response to Word, phrases, or picture that are presented on computer screen. Brain Fingerprinting is a controversial forensic science technique that uses electroencephalograph y (EEG to determine whether specific information is stored in a subject's brain

  11. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  12. Combined effects of brain-derived neurotrophic factor immobilized poly-lactic-co-glycolic acid membrane with human adipose-derived stem cells and basic fibroblast growth factor hydrogel on recovery of erectile dysfunction.

    Science.gov (United States)

    Lee, Seung Hwan; Kim, In Gul; Jung, Ae Ryang; Shrestha, Kshitiz Raj; Lee, Jin Ho; Park, Ki Dong; Chung, Byung Ha; Kim, Sae Woong; Kim, Ki Hean; Lee, Ji Youl

    2014-09-01

    Erectile dysfunction (ED) is the most frequent long-term problem after radical prostatectomy. We aimed to evaluate whether the use of combination therapy with basic fibroblast growth factor (bFGF)-hydrogel on corpus cavernosum and with adipose-derived stem cells (ADSCs) and brain-derived neurotrophic factor (BDNF)-immobilized poly-lactic-co-glycolic acid (PLGA) membrane on the cavernous nerve (CN) could improve erectile function in a rat model of bilateral cavernous nerve crush injury (BCNI). Rats were randomly divided into five groups (n=15 per group): a normal group (N group), a group receiving saline application after bilateral cavernous nerve crush injury (BCNI), a group undergoing bFGF-hydrogel injection in the corpus cavernosum after BCNI (bFGF), a group receiving ADSC application covered with BDNF-membrane after BCNI (ADSC/BDNF), and a group undergoing coadministration of bFGF-hydrogel injection and BDNF-membrane with ADSCs after BDNF (bFGF+ADSC/BDNF). Four weeks postoperatively, the erectile function was assessed by detecting the ratio of intracavernous pressure (ICP) to mean arterial pressure (MAP). Smooth muscle and collagen contents were measured using Masson's trichrome staining. Neuronal nitric oxide synthase (nNOS) expression in the dorsal penile nerve was detected by immunostaining. The protein expression of the α-smooth muscle actin (α-SMA) and the cyclic guanosine monophosphate (cGMP) level of the corpus cavernosum were quantified by western blot and cGMP assay, respectively. In the bFGF+ADSC/BDNF group, the erectile function was significantly elevated compared with the BCNI and other treated groups and showed a significantly increased smooth muscle/collagen ratio, nNOS content, α-SMA expression, and cGMP level. In particular, there were no statistical differences in the ICP/MAP ratio, smooth muscle/collagen ratio, and α-SMA and cGMP levels between the bFGF+ADSC/BDNF group and normal group. Application of the BDNF-immobilized PLGA membrane with

  13. BDNF对BMSCs向脑出血灶周围组织迁移的保护作用%Protective effect of brain derived neurotrophic factor on mesenchymal stem cells when transplanting to the surrounding issue of intracerebral hemorrhage stove

    Institute of Scientific and Technical Information of China (English)

    任瑞芳; 黄良国; 黄名璐; 蒋国红; 白洁

    2014-01-01

    目的 观察脑源性神经营养因子(BDNE)基因重组慢病毒转染骨髓间质干细胞(BMSCs)后,被移植入大鼠侧脑室内,向对侧脑出血灶周围组织的迁移情况. 方法 将60只脑出血模型大鼠按随机数字表法分为磷酸盐缓冲液(PBS)组、骨髓间质干细胞(BMSCs)组、骨髓间质干细胞-绿色荧光蛋白组(BMSCs-EGFP)、脑源性神经营养因子(BMSCs-EGFP-BDNF)组,每组15只.分别向侧脑室注射PBS,BMSCs,慢病毒(LV)转染的EGFP,LV转染的BDNF-EGFP,在术后7d、14d、21d采用Westen blotting检测各组BDNF在BMSCs中的蛋白表达,免疫荧光检测Brdu标记的BMSCs,EGFP及BDNF. 结果 Western blotting检测BMSCs-EGFP-BDNF组BDNF蛋白表达明显多于BMSCs组及BMSCs-EGFP组(P<0.05);细胞爬片BMSCs-EGFP-BDNF组BDNF荧光表达明显高于BMSCs组及BMSCs-EGFP组;脑组织切片免疫荧光单标显示BMSCs-EGFP-BDNF组迁移至脑出血灶周围组织的BMSCs阳性细胞数明显多于BMSCs组及BMSCs-EGFP组(P<0.05),BMSCs组与BMSCs-EGFP组除7d外,其余比较差异无统计学意义(P>0.05). 结论 基因重组慢病毒修饰的BMSCs中BDNF表达增高,提示BDNF对BMSCs向脑出血灶周围组织迁移具有保护作用.%Objective To observe the migration ofmesenchymal stem cells (MSCs) transfected with recombinant lentiviral vectors carried brain derived neurotrophic factor (BDNF) gene from lateral ventricle to intracerebral hemorrhage stove in rats and to discuss the protective effect of BDNF on MSCs.Methods Intracerebral hemorrhagic models were constructed in 60 SD rats and randomly divided into 4 groups:phosphate buffer solution (PBS) group,BMSCs group,BMSCs-enhanced green fluorescent protein (EGFP) group and BMSCs-EGFP-BDNF group (n=15); PBS,BMSCs,lentiviral vector (LV)carried EGFP and LV carried BDNF-EGFP were,respectively,injected into the lateral cerebral ventricle of each group; 7,14 and 21 d after the injection,BDNF protein expression in the BMSCs of each group was detected by

  14. Brain Development

    Science.gov (United States)

    ... Out More! New! Critical Competencies for Educators - Buy eBook Magic of Everyday Moments - Now with STEM View ... Out More! New! Critical Competencies for Educators - Buy eBook Magic of Everyday Moments - Now with STEM Support ...

  15. Brain surgery

    Science.gov (United States)

    Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... cut depends on where the problem in the brain is located. The surgeon creates a hole in ...

  16. Brain Malformations

    Science.gov (United States)

    Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, ...

  17. Brain Basics

    Medline Plus

    Full Text Available ... science, such as: How the brain develops How genes and the environment affect the brain The basic ... that with brain development in people mental disorders. Genes and environmental cues both help to direct this ...

  18. Brain Basics

    Medline Plus

    Full Text Available ... can lead to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits ... tailored treatments, and possibly prevention of such illnesses. The Working Brain Neurotransmitters Everything we do relies on ...

  19. The Impact of Neural Stem Cell Biology on CNS Carcinogenesis and Tumor Types

    Directory of Open Access Journals (Sweden)

    K. M. Kurian

    2011-01-01

    Full Text Available The incidence of gliomas is on the increase, according to epidemiological data. This increase is a conundrum because the brain is in a privileged protected site behind the blood-brain barrier, and therefore partially buffered from environmental factors. In addition the brain also has a very low proliferative potential compared with other parts of the body. Recent advances in neural stem cell biology have impacted on our understanding of CNS carcinogenesis and tumor types. This article considers the cancer stem cell theory with regard to CNS cancers, whether CNS tumors arise from human neural stem cells and whether glioma stem cells can be reprogrammed.

  20. Effect of brain-derived neurotrophic factor and green fluorescent protein gene-transfected neural stem cells transplantation on brain-derived neurotrophic factor expression in rats with spinal cord injury%BDNF-GFP转染神经干细胞对脊髓损伤大鼠BDNF表达的影响

    Institute of Scientific and Technical Information of China (English)

    王岩松; 梅晰凡; 吕刚

    2011-01-01

    Objective To study the effect of brain-derived neurotrophic factor (BDNF) and green fluorescent protein (GFP)transfected neural stem cells (NSCs) transplantation on expression of BDNF in rats with spinal cord injury. Methods NSCs were transfected with adenovirus vector bearing BDNF and GFP. Expression of BDNF in BDNF and GFP-transfected NSCs was detected by immunohistochemistry and Western blot, respectively. Of the 40 healthy Wistar rats, 8 were selected as a sham-operation group, 32 served as a T9 left hemisection model. Then, the 32 rats were randomly divided into BDNF and GFP-transfected NSCs transplantation group, GFP-transfected NSCs transplantation group, single NSCs transplantation group and model groups, 8 rats in each group. Gene-transfected NSCs or non gene-transfected NSCs were microinjected into each side of the transection site in the 3 NSCs transplantation groups after spinal cord injury (SCI) was induced. An equal volume of PBS was injected into the model group through the same injection sites. Expression of BDNF was detected in each group after SCI by real-time PCR. Results Immunohistochemistry showed that BDNF and GFP-transfected NSCs could express BDNF (yellow fluorescence). Western blot demonstrated that BDNF and GFP-transfected NSCs could express immunoreactive bands with a relative molecular mass of 41kU. NSCs transplantation could significantly increase the expression level of BDNF (P<0.01). The expression level of BDNF was the highest in BDNF and GFPtransfected NSCs transplantation group (P<0.01). Conclusion BDNF and GFP-transfected NSCs can survive and highly express BDNF in hemisected spinal cord model of rats.%目的 探讨脑源性神经营养因子(Brain-Derived Neurotrophic Factor,BDNF)和绿色荧光蛋白(Green Fluorescent Protein,GFP)转染后神经干细胞(Neural Stem Cells,NSCs)移植对脊髓损伤大鼠BDNF表达的影响.方法 以携带BDNF-GFP基因的腺病毒转染NSCs,免疫组化及Western blot检测转染后NSCs BDNF

  1. 不同胎龄人胎脑皮质额叶神经干细胞发育规律%Developmental features of neural stem cells in frontal cortex of embryonic human brain at various ages

    Institute of Scientific and Technical Information of China (English)

    尹晓娟; 封志纯

    2005-01-01

    BACKGROUND: Neural stem cells(NSCs) have been used to treat brain injury or some degenerating diseases of nervous system. Since in vitro culture conditions for NSCs differ from normal physiological conditions, whether the properties of the cultured cells are consistent with those of cells under physiological conditions? Therefore, inducing endogenous NSCs to proliferate and differentiate may be more promising for practise of NSCs.OBJECTIVE: This study was designed to investigate the developmental properties of NSCs in frontal cortex of embryonic human brain at various ages.DESIGN: It was a randomized experimental study.SETTING: This study was conducted at Department of Pediatrics, Zhujiang Hospital, Southern Medical University.PARTICIPANTS: Totally 90 16-to-36-week-old fetuses underwent inducing abortion by water bag were selected at the Obstetrics & Gynecology Department of Zhujiang Hospital Affiliated to Southern Medical University from October 2003 to March 2004. Brain tissue was taken from the frontal cortex of the aborted fetuses. All the mothers had normal physical examination findings. The informed consents on inducing abortion by water bag had been obtained from relatives and the mothers. The study was conducted with a prior permission from the competent department of the First Military Medical University. According to their ages, the fetuses were divided into 6 groups,16-week group, 20-week group, 24-week group, 28-week group and 36-week group, each group containing 15 cases.METHODS: After inducing abortion by water bag, under axenic conditions, the aborted fetus was dissected, with the scalp excisd, the skull opened and the membrane covering brain pull apart. Then the frontal cerebral cortex was taken out, fixed and sliced. Employing immunohistochemical staining and light microscope, distribution, morphological features, phenotypes, growth patterns and quantity of NSCs in the frontal cortex were observed. Morphological features of the cells and

  2. DI-3-butylphthalide-enhanced hematopoietic stem cell transplantation and endogenous stem cell mobilization for the treatment of cerebral infarcts

    Institute of Scientific and Technical Information of China (English)

    Baoquan Lu; Xiaoming Shang; Yongqiu Li; Hongying Ma; Chunqin Liu; Jianmin Li; Yingqi Zhang; Shaoxin Yao

    2011-01-01

    Exogenous stem cell transplantation and endogenous stem cell mobilization are both effective for the treatment of acute cerebral infarction. The compound dl-3-butylphthalide is known to improve microcirculation and help brain cells at the infarct loci. This experiment aimed to investigate the effects of dl-3-butylphthalide intervention based on the transplantation of hematopoietic stem cells and mobilization of endogenous stem cells in a rat model of cerebral infarction, following middle cerebral artery occlusion. Results showed that neurological function was greatly improved and infarct volume was reduced in rats with cerebral infarction. Data also showed that dl-3-butylphthalide can promote hematopoietic stem cells to transform into vascular endothelial cells and neuronal-like cells, and also enhance the therapeutic effect on cerebral infarction by hematopoietic stem cell transplantation and endogenous stem cell mobilization.

  3. Anatomy of the Brain

    Science.gov (United States)

    ... Menu Brain Tumor Information Brain Anatomy Brain Structure Neuron Anatomy Brain Tumor Symptoms Diagnosis Types of Tumors Risk Factors ... form Brain Tumor Information Brain Anatomy Brain Structure Neuron Anatomy Brain Tumor Symptoms Diagnosis Types of Tumors Risk Factors ...

  4. 三维可视化图像引导立体定位脑干及松果体区病灶活检术的研究%The technical report of three-dimension visualized image-guided stereotactic biopsy for lesions in pineal region and brain stem

    Institute of Scientific and Technical Information of China (English)

    王亚明; 于新; 李志超; 惠瑞; 刘锐; 尹丰; 张雷鸣; 程岗; 张剑宁

    2015-01-01

    Objective To investigate the methodology,technical essential and significance of threedimension visualized image-guided stereotactic biopsy (SB) for lesions in pineal region and brain stem.Methods A total of 88 cases of lesions in pineal region and brain stem underwent image-guided SB in our department were retrospectively studied.Frame-based and CAS-2 type frameless SBs were performed in 57 and 31 cases respectively.Pre-biopsy three-dimension visualized image reconstruction was performed by SB planning software and the structure related to possible trajectory in each image slice was confirmed.The most suitable trajectory was selected accordingly.For lesions in pineal region,anterior-frontal trans-tentorium cerebella hiatus trajectory for avoiding tentorial margin was used.For lesions in mesencephalon,posteriorfrontal trans-lateral ventrical-thalamus trajectory via the vertical axis of brain stem was used.For pontal lesions,supra-occipital trans-pedunculus cerebellaris medius trajectory was used.Results Histological diagnosis was established in all 88 cases,which gave a high diagnostic yield (100%).Fifty-six lesions (64%) located in brain stem (middle brain and pons) and 32 (36%) in pineal region.In 56 brain stem lesions,there were 38 cases (68%) of glioma,3(5%) lymphoma,2(4%) neurodegenerative disease,6 (11%) multiple sclerosis and tumefactive demyelinating lesion,2 (4%) non-specific inflammation,2 (4%)brain infarct,2(4%) brain metastases,and 1 (2%) radiation necrosis.For lesions in pineal region,there were 18 cases (56%) of germ cell tumor,4(13%) glioma,9 (28%) pineal cell tumor,and 1 (3%) Wemicke encephalopathy.One case (1%) died of biopsy-related hemorrhage.The neurological deficits became severe because of hemorrhage in 5 cases,the medical treatment was adopted in 3 cases (3%)and drainage in 2 (2%).Conclusions Stereotactic biopsy for lesions in pineal region and brain stem was a safe and effective procedure that could help

  5. Stem cell therapy for Alzheimer's disease.

    Science.gov (United States)

    Abdel-Salam, Omar M E

    2011-06-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder which impairs the memory and intellectual abilities of the affected individuals. Loss of episodic as well as semantic memory is an early and principal feature. The basal forebrain cholinergic system is the population of neurons most affected by the neurodegenerative process. Extracellular as well as intracellular deposition of beta-amyloid or Abeta (Abeta) protein, intracellular formation of neurofibrillary tangles and neuronal loss are the neuropathological hallmarks of AD. In the last few years, hopes were raised that cell replacement therapy would provide cure by compensating the lost neuronal systems. Stem cells obtained from embryonic as well as adult tissue and grafted into the intact brain of mice or rats were mostly followed by their incorporation into the host parenchyma and differentiation into functional neural lineages. In the lesioned brain, stem cells exhibited targeted migration towards the damaged regions of the brain, where they engrafted, proliferated and matured into functional neurones. Neural precursor cells can be intravenously administered and yet migrate into brain damaged areas and induce functional recovery. Observations in animal models of AD have provided evidence that transplanted stem cells or neural precursor cells (NPCs) survive, migrate, and differentiate into cholinergic neurons, astrocytes, and oligodendrocytes with amelioration of the learning/memory deficits. Besides replacement of lost or damaged cells, stem cells stimulate endogenous neural precursors, enhance structural neuroplasticity, and down regulate proinflammatory cytokines and neuronal apoptotic death. Stem cells could also be genetically modified to express growth factors into the brain. In the last years, evidence indicated that the adult brain of mammals preserves the capacity to generate new neurons from neural stem/progenitor cells. Inefficient adult neurogenesis may contribute to the

  6. 叶酸联合成体神经干细胞治疗创伤性脑损伤大鼠的实验%Study on Folic Acid Combined with Adult Neural Stem Cells in the Treatment of Traumatic Brain Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    刁波; 刘琴; 王丽萍; 张宜

    2012-01-01

    Objective To explore the folic acid and adult neural stem cells' joint influencing mechanism on the rat with Traumatic Brain Injury, and to find out its possible mechanism. Methods Divide 120 rats to 6 groups randomly—normal group, mode group, sham operation group, folacin injection group, adult stem cells transplant group, and folacin injection plus adult stem cells transplant group. Observe the morphological change under the microscope, then, do flow cytometry test and detect the expression of the neural stem cells' facial notation—CD105 、 CD45、CD44、 CD29. Examine the expression of neuron special enolase( NSE) and the expression of gelatinous fibre acidic protein (GFAP) with imimmofluorescenee. Examine the rats' ability to motor-coordinate and conform with balance beam. Test each group' s learning and memorizing ability by conducting the Morris water maze experiment. Then, conduct the HE chromosome and Brdu immunohistochemistry experiment to detect morphological change of the brain tissue. After this, do the enzyme-linked immunosorbent assay (ELISA) to detect the expression of brain-derived neurotrophic factor( BDNF) and the expression of nerve growth factor. The last but not least, use western blotting to examine the expression of related dead protein in the brain tissue;BCL-2、Bax、Caspase-3. Results The separated cells can be vitro subcultured, by doing flow cytometry test, we find that positive cells express CD44 and CD29 while negative express CD105, CD45. Cells induced by fetal bovine serum can produce NSE or GFAP positive cells. Experiments suggest that traumatic brain injured rats can significantly improve their behavior after jointly influenced by the folie acid and adult neural stem cells. Besides , they can also reduce brain tissue inflammation, restore damaged nerve cells, increase brain tissue of BDNF and NGFs content, increase BCL 2 expression, and lower the expression of Bax, caspase-3. Conclusion The folic acid combined with adull

  7. 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

    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......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...... 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...

  8. Scans Show Range of Zika-Linked Infant Brain Defects

    Science.gov (United States)

    ... brain stem abnormalities, calcifications, and a condition called ventriculomegaly, where the ventricles (fluid filled spaces in the ... the confirmed or suspected Zika infection groups had ventriculomegaly, the researchers said. Most fetuses also had at ...

  9. Brain Basics

    Medline Plus

    Full Text Available ... have been linked to many mental disorders, including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain ... studies show that brain growth in children with autism appears to peak early. And as they grow ...

  10. Brain Basics

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    Full Text Available ... depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of ... but sometimes give rise to disabilities or diseases. neural circuit —A network of neurons and their interconnections. ...

  11. Brain Basics

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    Full Text Available ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ... depression experience when starting treatment. Gene Studies Advanced technologies are also making it faster, easier, and more ...

  12. Brain Basics

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    Full Text Available ... Real Life Brain Basics in Real Life—How Depression affects the Brain Meet Sarah Sarah is a ... blues" from time to time. In contrast, major depression is a serious disorder that lasts for weeks. ...

  13. Brain Basics

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    Full Text Available ... the brain cannot effectively coordinate the billions of cells in the body, the results can affect many ... unit of the brain and nervous system. These cells are highly specialized for the function of conducting ...

  14. Brain Diseases

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    The brain is the control center of the body. It controls thoughts, memory, speech, and movement. It regulates the function of many organs. When the brain is healthy, it works quickly and automatically. However, ...

  15. Brain Basics

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    Full Text Available ... related to changes in the anatomy, physiology, and chemistry of the nervous system. When the brain cannot ... their final destination. Chemical signals from other cells guide neurons in forming various brain structures. Neighboring neurons ...

  16. Brain Basics

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    Full Text Available ... in the anatomy, physiology, and chemistry of the nervous system. When the brain cannot effectively coordinate the billions ... the basic working unit of the brain and nervous system. These cells are highly specialized for the function ...

  17. Brain Basics

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    Full Text Available ... affect many aspects of life. Scientists are continually learning more about how the brain grows and works ... early brain development. It may also assist in learning and memory. Problems in making or using glutamate ...

  18. Stem Cells for the Treatment of Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Ning Zhang

    2010-09-01

    Full Text Available Neurodegenerative diseases are characterized by neurodegenerative changes or apoptosis of neurons involved in networks, leading to permanent paralysis and loss of sensation below the site of the injury. Cell replacement therapy has provided the basis for the development of potentially powerful new therapeutic strategies for a broad spectrum of human neurological diseases. In recent years, neurons and glial cells have successfully been generated from stem cells, and extensive efforts by investigators to develop stem cell-based brain transplantation therapies have been carried out. We review here notable previously published experimental and preclinical studies involving stem cell-based cell for neurodegenerative diseases and discuss the future prospects for stem cell therapy of neurological disorders in the clinical setting. Steady and solid progress in stem cell research in both basic and preclinical settings should support the hope for development of stem cell-based cell therapies for neurological diseases.

  19. Induced pluripotent stem cells and Parkinson's disease: modelling and treatment.

    Science.gov (United States)

    Xu, Xiaoyun; Huang, Jinsha; Li, Jie; Liu, Ling; Han, Chao; Shen, Yan; Zhang, Guoxin; Jiang, Haiyang; Lin, Zhicheng; Xiong, Nian; Wang, Tao

    2016-02-01

    Many neurodegenerative disorders, such as Parkinson's disease (PD), are characterized by progressive neuronal loss in different regions of the central nervous system, contributing to brain dysfunction in the relevant patients. Stem cell therapy holds great promise for PD patients, including with foetal ventral mesencephalic cells, human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). Moreover, stem cells can be used to model neurodegenerative diseases in order to screen potential medication and explore their mechanisms of disease. However, related ethical issues, immunological rejection and lack of canonical grafting protocols limit common clinical use of stem cells. iPSCs, derived from reprogrammed somatic cells, provide new hope for cell replacement therapy. In this review, recent development in stem cell treatment for PD, using hiPSCs, as well as the potential value of hiPSCs in modelling for PD, have been summarized for application of iPSCs technology to clinical translation for PD treatment.

  20. Neural stem cells could serve as a therapeutic material forage-related neurodegenerative diseases

    Institute of Scientific and Technical Information of China (English)

    Sarawut Suksuphew; Parinya Noisa

    2015-01-01

    Progressively loss of neural and glial cells is the keyevent that leads to nervous system dysfunctions anddiseases. Several neurodegenerative diseases, forinstance Alzheimer's disease, Parkinson's disease, andHuntington's disease, are associated to aging andsuggested to be a consequence of deficiency of neuralstem cell pool in the affected brain regions. Endogenousneural stem cells exist throughout life and are found inspecific niches of human brain. These neural stem cellsare responsible for the regeneration of new neurons torestore, in the normal circumstance, the functions of thebrain. Endogenous neural stem cells can be isolated,propagated, and, notably, differentiated to most celltypes of the brain. On the other hand, other types ofstem cells, such as mesenchymal stem cells, embryonicstem cells, and induced pluripotent stem cells can alsoserve as a source for neural stem cell production, thathold a great promise for regeneration of the brain. Thereplacement of neural stem cells, either endogenousor stem cell-derived neural stem cells, into impairedbrain is highly expected as a possible therapeutic meanfor neurodegenerative diseases. In this review, clinicalfeatures and current routinely treatments of agerelatedneurodegenerative diseases are documented.Noteworthy, we presented the promising evidence ofneural stem cells and their derivatives in curing suchdiseases, together with the remaining challenges toachieve the best outcome for patients.

  1. Brain Basics

    Medline Plus

    Full Text Available ... such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit ... final destination. Chemical signals from other cells guide neurons in forming various brain structures. Neighboring neurons make connections with each other ...

  2. Brain Aneurysm

    Science.gov (United States)

    A brain aneurysm is an abnormal bulge or "ballooning" in the wall of an artery in the brain. They are sometimes called berry aneurysms because they ... often the size of a small berry. Most brain aneurysms produce no symptoms until they become large, ...

  3. The Brain.

    Science.gov (United States)

    Hubel, David H.

    1979-01-01

    This article on the brain is part of an entire issue about neurobiology and the question of how the human brain works. The brain as an intricate tissue composed of cells is discussed based on the current knowledge and understanding of its composition and structure. (SA)

  4. Effect of acupuncture liver channel of points on content of G protein alpha subunits in the rat brain stem after nitroglycerin infusion%针刺肝经腧穴对偏头痛大鼠脑干组织G蛋白含量的影响

    Institute of Scientific and Technical Information of China (English)

    钟广伟; 李炜; 王素娥; 李臻琰; 文玲波

    2004-01-01

    目的研究针刺肝经腧穴对实验性偏头痛大鼠肝干组织G蛋白亚基(Gsa和Gia)含量的影响.方法通过皮下注射硝酸甘油(10mg/kg)建立实验性偏头痛大鼠模型,将动物随机分成正常对照组、生理盐水组、模型对照组和针刺治疗组,运用免疫印迹法(Western b1ot)检测脑干组织Gia和Gsa的含量.结果皮下注射硝酸甘油4h后脑干组织Gsa蛋白含量明显升高(P<0.01),Gia蛋白含量明显降低(P<0.01),Gsa/Gia蛋白比值升高;针刺治疗组与模型组比较,脑干组织中Gsa蛋白含量明显降低(P<0.01),Gia蛋白含量明显升高(P<0.01),Gsa/Gia蛋白比值降低.结论偏头痛发作可能与大鼠脑干组织G蛋白信号传导系统功能障碍有关,针刺介导的G蛋白信号通路可能是其防治偏头痛的重要机制之一.%Objective: In order to explore the effect of acupuncture the liver channel of points on the content of G protein alpha subunits in the rat brain stem after nitroglycerin infusion. Methods: The model of migraine rats were reproduced in accordance with Knynihar-tassorelli methods by infusing the NO lonor nitroglycerin [glyceryl trintrate (GTN)] i.h, then the rats were divided randomly into four groups: Normal control group, Saline control group, Model control group and Acupuncture treatment group. The content of Giα and Gsα protein in the rat brain stem was analysed by western blot method. Results: The model control group of the content of Gsα protein in the rat brain stem was significantly raised (P <0.01), the Giα protein was significantly reduced (P <0.01), and the ration of Gsα/Giα was increased by comparison with the normal control group. The acupuncture group of Gsα protein in the rat brain stem went up apparently than the model group (P <0.01), and Giα protein was slightly higher than the model group (P <0.01), resulting in reducing of Gsα/Giα rations. Conclusion: Our results provided important information for understanding how

  5. 神经干细胞治疗甲基丙二酸血症继发脑损伤4例临床观察%Clinical observation of neural stem cells in treatment of 4 patients with methylmalonic acidemia secondary to brain injury

    Institute of Scientific and Technical Information of China (English)

    杨辉; 屈素清; 刘卫鹏; 杜侃; 杨印祥; 栾佐

    2014-01-01

    Objective To observe the neural stem cell therapeutic effect with methylmalonic acidemia(MMA) secondary to brain injury.Methods From April 2008 to October 2010, 4 patients with methylmalonic acidemia secondary to brain injury admitted to our hospital .All the patients re-ceived the neural stem cell transplantation via ventricle puncture positioned by MRI , and all the pa-tients were given a follow-up at 1 month and 6 month after the transplantation with Gesell scales assessment .Results Three of the four patients got improvements in motor and fine skills , visual and intellectual reactions after the transplantation within 1 month.In the following 6 months the conti-nuing improvements could be observed after the transplantation among the 3 patients.Cell therapy did not appear irreversible adverse events .Conclusion Neural stem cell therapy is safe and reliable , it can improve the clinical manifestations in children with methylmalonic academia secondary to brain injury in a short time .The efficacy can sustain to 6 months after the transplantation .On the basis of the treatment for the cause , the neural stem cell transplantation provides a new method of treatment for methylmalonic acidemia secondary to brain injury .But the long-term effect needs a further follow-up observation .%目的:观察神经干细胞治疗甲基丙二酸血症继发脑损伤儿童的临床疗效。方法2008年4月-2010年10月在我院治疗的甲基丙二酸血症继发脑损伤儿童4例,所有患儿均在磁共振头皮定位下行侧脑室穿刺神经干细胞移植。移植后1个月对患儿综合评估,并随访至移植后6个月,对患儿行Gesell发育量表评估。结果4例中,3例在移植后1个月内出现大运动、精细动作、视听反应及智力反应等方面的进步;跟踪随访至移植后6个月,3例均持续出现不同程度进步。细胞治疗均未出现不可逆不良事件。结论神经干细胞治疗安全可靠,能在短时间改善

  6. Neural stem cell-based treatment for neurodegenerative diseases.

    Science.gov (United States)

    Kim, Seung U; Lee, Hong J; Kim, Yun B

    2013-10-01

    Human neurodegenerative diseases such as Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) are caused by a loss of neurons and glia in the brain or spinal cord. Neurons and glial cells have successfully been generated from stem cells such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs) and neural stem cells (NSCs), and stem cell-based cell therapies for neurodegenerative diseases have been developed. A recent advance in generation of a new class of pluripotent stem cells, induced pluripotent stem cells (iPSCs), derived from patients' own skin fibroblasts, opens doors for a totally new field of personalized medicine. Transplantation of NSCs, neurons or glia generated from stem cells in animal models of neurodegenerative diseases, including PD, HD, ALS and AD, demonstrates clinical improvement and also life extension of these animals. Additional therapeutic benefits in these animals can be provided by stem cell-mediated gene transfer of therapeutic genes such as neurotrophic factors and enzymes. Although further research is still needed, cell and gene therapy based on stem cells, particularly using neurons and glia derived from iPSCs, ESCs or NSCs, will become a routine treatment for patients suffering from neurodegenerative diseases and also stroke and spinal cord injury.

  7. Adult stem cell transplantation in stroke: its limitations and prospects.

    Science.gov (United States)

    Roh, Jae-Kyu; Jung, Keun-Hwa; Chu, Kon

    2008-09-01

    A growing number of studies have demonstrated stem cell-based therapy provides a feasible, realistic approach to the restoration of lost brain function after stroke. Moreover, adult stem cells may provide more appropriate clinical strategies. Leading candidate sources include bone marrow, peripheral blood, adipose tissue, skeletal muscle, and olfactory mucosa, which act as central repositories for multipotent stem cells that can repopulate neural tissues. The medical society is currently enthusiastic concerning the clinical applications of autologous adult stem cells in stroke, based on promising results obtained during experimental studies and initial clinical trials. However, before embracing clinical applications, several essential precautions must be properly addressed. For example, the regenerative potentials of adult stem cells decline with age, and stem cells isolated from aged patients may retain dysfunctional characteristics. Are the natures and amounts of available autologous cells appropriate for therapeutic application in stroke? Do transplanted cells remain functional in the diseased brain, and if so what are the optimal injection routes, cell doses, and timings? Thus, we believe that success in future clinical trials will depend on careful investigation at the experimental level, to allow us to understand not only the practicalities of stem cell use, but also the underlying biological principles involved. Here, we review the advantages and disadvantages of the different adult stem cell sources and discuss the challenges that must be negotiated to achieve transplantation success.

  8. Recent advances in stem cell neurobiology.

    Science.gov (United States)

    Ostenfeld, T; Svendsen, C N

    2003-01-01

    1. Neural stem cells can be cultured from the CNS of different mammalian species at many stages of development. They have an extensive capacity for self-renewal and will proliferate ex vivo in response to mitogenic growth factors or following genetic modification with immortalising oncogenes. Neural stem cells are multipotent since their differentiating progeny will give rise to the principal cellular phenotypes comprising the mature CNS: neurons, astrocytes and oligodendrocytes. 2. Neural stem cells can also be derived from more primitive embryonic stem (ES) cells cultured from the blastocyst. ES cells are considered to be pluripotent since they can give rise to the full cellular spectrum and will, therefore, contribute to all three of the embryonic germ layers: endoderm, mesoderm and ectoderm. However, pluripotent cells have also been derived from germ cells and teratocarcinomas (embryonal carcinomas) and their progeny may also give rise to the multiple cellular phenotypes contributing to the CNS. In a recent development, ES cells have also been isolated and grown from human blastocysts, thus raising the possibility of growing autologous stem cells when combined with nuclear transfer technology. 3. There is now an emerging recognition that the adult mammalian brain, including that of primates and humans, harbours stem cell populations suggesting the existence of a previously unrecognised neural plasticity to the mature CNS, and thereby raising the possibility of promoting endogenous neural reconstruction. 4. Such reports have fuelled expectations for the clinical exploitation of neural stem cells in cell replacement or recruitment strategies for the treatment of a variety of human neurological conditions including Parkinson's disease (PD), Huntington's disease, multiple sclerosis and ischaemic brain injury. Owing to their migratory capacity within the CNS, neural stem cells may also find potential clinical application as cellular vectors for widespread gene

  9. 移植的神经干细胞在MPTP诱导的帕金森病小鼠脑内的存活与分化%Survival and differentiation of transplanted neural stem cells in mice brain with MPTP-induced Parkinson disease

    Institute of Scientific and Technical Information of China (English)

    李学坤; 郭安臣; 左萍萍

    2003-01-01

    AIM: To determine survival and differentiation of cultured neural stem cells (NSCs) into viable and functional neurons upon transplantation into mice brain of MPTP-induced Parkinson disease (PD). METHODS: Mouse model of PD was established with two subcutaneous (sc) injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 40 mg/kg) twice, 16 h apart. NSCs isolated from rat embryo midbrain were cultured in clonal density.After labeled with 5-bromo-2'-deoxyuridine (BrdU), the NSCs were transplanted into the uni- or bi-lateral striatum of PD mouse. Tyrosine hydroxylase (TH) immunofluorescence was used to evaluate the toxicity of MPTP on theneural cells in the substantia nigra. Immunohistology and laser confocal microscope were used to detect the survival and differentiation of transplanted NSCs. RESULTS: The cultured NSCs generated neurospheres and differentiated into neuron and astrocyte. It indicated that the cultured NSCs were multipotent and self-renewal in vitro.TH-positive neural cells were significantly reduced in the substantia nigra. Immunohistology showed that the uni- or bi-lateral transplanted NSCs survived in the brain of PD model mouse. Laser confocal microscope indicated that some transplanted NSCs could properly differentiate into targeted TH-positive neural cells in vivo. CONCLUSION:The transplanted multipotent NSCs could survive and differentiate into functional dopamine neurons.

  10. Stem Cell Transplant

    Science.gov (United States)

    ... transplant is a procedure that infuses healthy blood stem cells into your body to replace your damaged or ... A bone marrow transplant is also called a stem cell transplant. A bone marrow transplant may be necessary ...

  11. Tracking adult stem cells.

    Science.gov (United States)

    Snippert, Hugo J; Clevers, Hans

    2011-02-01

    The maintenance of stem-cell-driven tissue homeostasis requires a balance between the generation and loss of cell mass. Adult stem cells have a close relationship with the surrounding tissue--known as their niche--and thus, stem-cell studies should preferably be performed in a physiological context, rather than outside their natural environment. The mouse is an attractive model in which to study adult mammalian stem cells, as numerous experimental systems and genetic tools are available. In this review, we describe strategies commonly used to identify and functionally characterize adult stem cells in mice and discuss their potential, limitations and interpretations, as well as how they have informed our understanding of adult stem-cell biology. An accurate interpretation of physiologically relevant stem-cell assays is crucial to identify adult stem cells and elucidate how they self-renew and give rise to differentiated progeny.

  12. Neurotrophin signaling in cancer stem cells.

    Science.gov (United States)

    Chopin, Valérie; Lagadec, Chann; Toillon, Robert-Alain; Le Bourhis, Xuefen

    2016-05-01

    Cancer stem cells (CSCs), are thought to be at the origin of tumor development and resistance to therapies. Thus, a better understanding of the molecular mechanisms involved in the control of CSC stemness is essential to the design of more effective therapies for cancer patients. Cancer cell stemness and the subsequent expansion of CSCs are regulated by micro-environmental signals including neurotrophins. Over the years, the roles of neurotrophins in tumor development have been well established and regularly reviewed. Especially, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are reported to stimulate tumor cell proliferation, survival, migration and/or invasion, and favors tumor angiogenesis. More recently, neurotrophins have been reported to regulate CSCs. This review briefly presents neurotrophins and their receptors, summarizes their roles in different cancers, and discusses the emerging evidence of neurotrophins-induced enrichment of CSCs as well as the involved signaling pathways.

  13. Targeting the osteosarcoma cancer stem cell

    Directory of Open Access Journals (Sweden)

    Qin Ling

    2010-10-01

    Full Text Available Abstract Osteosarcoma is the most common type of solid bone cancer and the second leading cause of cancer-related death in pediatric patients. Many patients are not cured by the current osteosarcoma therapy consisting of combination chemotherapy along with surgery and thus new treatments are urgently needed. In the last decade, cancer stem cells have been identified in many tumors such as leukemia, brain, breast, head and neck, colon, skin, pancreatic, and prostate cancers and these cells are proposed to play major roles in drug resistance, tumor recurrence, and metastasis. Recent studies have shown evidence that osteosarcoma also possesses cancer stem cells. This review summarizes the current knowledge about the osteosarcoma cancer stem cell including the methods used for its isolation, its properties, and its potential as a new target for osteosarcoma treatment.

  14. 自体骨髓间充质干细胞移植治疗颅脑损伤后痉挛性瘫痪%S pastic paralysis after traumatic brain injury treated by autologous bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    伊西才; 魏礼洲; 黑悦; 龙乾发; 王博晨; 田沁涛; 周跃飞; 刘卫平

    2016-01-01

    目的:探讨应用自体骨髓间充质干细胞治疗颅脑损伤后痉挛性瘫痪的临床疗效。方法回顾性分析第四军医大学西京医院神经外科自2009年5月至2014年4月治疗的33例颅脑损伤后痉挛性瘫痪患者,完成4次自体骨髓间充质干细胞移植,每周1次,每次经腰椎穿刺蛛网膜下腔注射,细胞数为2×107,移植前、移植后1个月、3个月、6个月通过改良Ashworth分级、Brunnstrom分级评估患侧上下肢肌张力、运动功能,并行脑PET/CT、脑电图、偏瘫肢体肌电图检查。结果移植后1个月开始Brunnstrom分级较移植前改善。移植后3个月开始Ashworth分级较移植前改善。5例移植后3个月头颅PET/CT见脑葡萄糖代谢减低较前改善。临床观察未发现明显不良反应,脑电图、偏瘫肢体肌电图检查未见明显变化。结论自体骨髓间充质干细胞移植对颅脑损伤后痉挛性瘫痪的肢体肌张力增高和运动障碍均有改善,移植后6个月内通过临床观察及影像学检查未发现不良反应,为临床治疗颅脑损伤后遗症提供了新方法。%Objective To investigate the clinical efficacy of autologous bone marrow mesenchymal stem cells transplantation on spastic paralysis after traumatic brain injury. Methods During May 2009 to April 2014, the clinical data about 33 patients with spastic paralysis after traumatic brain injury were retrospectively analyzed. Bone marrow puncture was performed under general anesthesia. Bone marrow mesenchymal stem cells (2 ×107) were intrathecally transplanted once a week for four weeks. The measurement points contain before treatment, one month, three months and six months after treatment. Muscular tension and movement disorders were evaluated using modified Ashworth scale and Brunnstrom stage classification respectively. Besides that, brain PET/CT, electroencephalo-graphy and electromyography were recorded. Results Muscular tone was improved one

  15. Tracking adult stem cells

    NARCIS (Netherlands)

    Snippert, H.J.G.; Clevers, H.

    2011-01-01

    The maintenance of stem-cell-driven tissue homeostasis requires a balance between the generation and loss of cell mass. Adult stem cells have a close relationship with the surrounding tissue--known as their niche--and thus, stem-cell studies should preferably be performed in a physiological context,

  16. Stereotactic Radiosurgery in Treating Patients With Brain Tumors

    Science.gov (United States)

    2012-03-21

    Adult Central Nervous System Germ Cell Tumor; Adult Malignant Meningioma; Adult Medulloblastoma; Adult Noninfiltrating Astrocytoma; Adult Oligodendroglioma; Adult Craniopharyngioma; Adult Meningioma; Brain Metastases; Adult Ependymoma; Adult Pineal Parenchymal Tumor; Adult Brain Stem Glioma; Adult Infiltrating Astrocytoma; Mixed Gliomas; Stage IV Peripheral Primitive Neuroectodermal Tumor

  17. Mind, Brain and Education: A Decade of Evolution

    Science.gov (United States)

    Schwartz, Marc

    2015-01-01

    This article examines the evolution of Mind, Brain, and Education (MBE), the field, alongside that of the International Mind, Brain and Education Society (IMBES). The reflections stem mostly from my observations while serving as vice president, president-elect, and president of IMBES during the past 10 years. The article highlights the evolution…

  18. 小鼠胚胎干细胞移植入成体大鼠脑内的区域特异性存活与分化%Regionspecific survival and differentiation of mouse embryonic stem cell-derived implants in the adult rat brain

    Institute of Scientific and Technical Information of China (English)

    鲁文果; 陈红; 王东; 黎逢光; 张苏明

    2007-01-01

    Totipotent and regionally non-specified embryonic stem (ES) cells provide a powerful tool to understand mechanisms controlling stem cell differentiation in different regions of the adult brain. As the development capacity of ES cells in the adult brain is still largely unknown, we grafted small amounts of mouse ES (mES) cells into adult rat brains to explore the survival and differentiation of implanted mES cells in different rat brain regions. We transplanted the green fluorescent protein (GFP)-positive mES cells into the hippocampus, septal area, cortex and caudate nucleus in rat brains. Then the rats were sacrificed 5,14 and 28 d later. Of all the brain regions, the survival rate of the transplanted cells and their progeny were the highest in the hippocampus and the lowest in the septal area (P<0.01). The grafted ES cells could differentiate into nestin-positive neural stem cells. Nestin-positive/GFP-positive cells were observed in all brain regions with the highest frequency of nestin-positive cells in the hippocampus and the lowest in the medial septal area (P<0.01). mES cells differentiated into end cells such as neurons and glial cells in all transplantation sites in recipient brains. In the hippocampus, the ES cells differentiated into neurons in large amounts. These results demonstrate that only some brain regions permit survival of mES cells and their progeny, and form instructive environments for neuronal differentiation of mES cells. Thus, because of regionspecific presence of microenvironmental cues and their environmental fields, the characteristics of the recipient tissue were considerably important in formulating cell replacement strategies for neural disorders.%全能区域非特异性的胚胎干细胞是研究成体不同脑区控制干细胞分化能力的十分有力的工具.胚胎干细胞源性神经前体细胞移植入成体脑后可分化为功能性神经元,但是未分化的胚胎干细胞在成体脑内各个部位的存活、生

  19. TOPICAL REVIEW: Stem cells engineering for cell-based therapy

    Science.gov (United States)

    Taupin, Philippe

    2007-09-01

    Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.

  20. Brain Autopsy

    Science.gov (United States)

    ... why a family should consider arranging for a brain autopsy upon the death of their loved one. To get a definitive ... study of tissue removed from the body after death. Examination of the whole brain is important in understanding FTD because the patterns ...

  1. Brain Basics

    Medline Plus

    Full Text Available ... Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of ... to slow or stop them from progressing. Functional magnetic resonance imaging (fMRI) is another important research tool in understanding ...

  2. Brain Basics

    Medline Plus

    Full Text Available ... and are working to compare that with brain development in people mental disorders. Genes and environmental cues both help to direct ... comparing such children to those with normal brain development may help scientists to pinpoint when and where mental disorders begin and perhaps how to slow or stop ...

  3. Neural Induction, Neural Fate Stabilization, and Neural Stem Cells

    Directory of Open Access Journals (Sweden)

    Sally A. Moody

    2002-01-01

    Full Text Available The promise of stem cell therapy is expected to greatly benefit the treatment of neurodegenerative diseases. An underlying biological reason for the progressive functional losses associated with these diseases is the extremely low natural rate of self-repair in the nervous system. Although the mature CNS harbors a limited number of self-renewing stem cells, these make a significant contribution to only a few areas of brain. Therefore, it is particularly important to understand how to manipulate embryonic stem cells and adult neural stem cells so their descendants can repopulate and functionally repair damaged brain regions. A large knowledge base has been gathered about the normal processes of neural development. The time has come for this information to be applied to the problems of obtaining sufficient, neurally committed stem cells for clinical use. In this article we review the process of neural induction, by which the embryonic ectodermal cells are directed to form the neural plate, and the process of neural�fate stabilization, by which neural plate cells expand in number and consolidate their neural fate. We will present the current knowledge of the transcription factors and signaling molecules that are known to be involved in these processes. We will discuss how these factors may be relevant to manipulating embryonic stem cells to express a neural fate and to produce large numbers of neurally committed, yet undifferentiated, stem cells for transplantation therapies.

  4. Brain peroxisomes.

    Science.gov (United States)

    Trompier, D; Vejux, A; Zarrouk, A; Gondcaille, C; Geillon, F; Nury, T; Savary, S; Lizard, G

    2014-03-01

    Peroxisomes are essential organelles in higher eukaryotes as they play a major role in numerous metabolic pathways and redox homeostasis. Some peroxisomal abnormalities, which are often not compatible with life or normal development, were identified in severe demyelinating and neurodegenerative brain diseases. The metabolic roles of peroxisomes, especially in the brain, are described and human brain peroxisomal disorders resulting from a peroxisome biogenesis or a single peroxisomal enzyme defect are listed. The brain abnormalities encountered in these disorders (demyelination, oxidative stress, inflammation, cell death, neuronal migration, differentiation) are described and their pathogenesis are discussed. Finally, the contribution of peroxisomal dysfunctions to the alterations of brain functions during aging and to the development of Alzheimer's disease is considered.

  5. Plant stem cell niches.

    Science.gov (United States)

    Aichinger, Ernst; Kornet, Noortje; Friedrich, Thomas; Laux, Thomas

    2012-01-01

    Multicellular organisms possess pluripotent stem cells to form new organs, replenish the daily loss of cells, or regenerate organs after injury. Stem cells are maintained in specific environments, the stem cell niches, that provide signals to block differentiation. In plants, stem cell niches are situated in the shoot, root, and vascular meristems-self-perpetuating units of organ formation. Plants' lifelong activity-which, as in the case of trees, can extend over more than a thousand years-requires that a robust regulatory network keep the balance between pluripotent stem cells and differentiating descendants. In this review, we focus on current models in plant stem cell research elaborated during the past two decades, mainly in the model plant Arabidopsis thaliana. We address the roles of mobile signals on transcriptional modules involved in balancing cell fates. In addition, we discuss shared features of and differences between the distinct stem cell niches of Arabidopsis.

  6. Lung Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Sharon R. Pine

    2008-01-01

    Full Text Available Lung cancer remains a major cause of cancer-related lethality because of high incidence and recurrence in spite of significant advances in staging and therapies. Recent data indicates that stem cells situated throughout the airways may initiate cancer formation. These putative stem cells maintain protumorigenic characteristics including high proliferative capacity, multipotent differentiation, drug resistance and long lifespan relative to other cells. Stem cell signaling and differentiation pathways are maintained within distinct cancer types, and destabilization of this machinery may participate in maintenance of cancer stem cells. Characterization of lung cancer stem cells is an area of active research and is critical for developing novel therapies. This review summarizes the current knowledge on stem cell signaling pathways and cell markers used to identify the lung cancer stem cells.

  7. Hypoxic preconditioning enhances neural stem cell transplantation therapy after intracerebral hemorrhage in mice.

    Science.gov (United States)

    Wakai, Takuma; Narasimhan, Purnima; Sakata, Hiroyuki; Wang, Eric; Yoshioka, Hideyuki; Kinouchi, Hiroyuki; Chan, Pak H

    2016-12-01

    Previous studies have shown that intraparenchymal transplantation of neural stem cells ameliorates neurological deficits in animals with intracerebral hemorrhage. However, hemoglobin in the host brain environment causes massive grafted cell death and reduces the effectiveness of this approach. Several studies have shown that preconditioning induced by sublethal hypoxia can markedly improve the tolerance of treated subjects to more severe insults. Therefore, we investigated whether hypoxic preconditioning enhances neural stem cell resilience to the hemorrhagic stroke environment and improves therapeutic effects in mice. To assess whether hypoxic preconditioning enhances neural stem cell survival when exposed to hemoglobin, neural stem cells were exposed to 5% hypoxia for 24 hours before exposure to hemoglobin. To study the effectiveness of hypoxic preconditioning on grafted-neural stem cell recovery, neural stem cells subjected to hypoxic preconditioning were grafted into the parenchyma 3 days after intracerebral hemorrhage. Hypoxic preconditioning significantly enhanced viability of the neural stem cells exposed to hemoglobin and increased grafted-cell survival in the intracerebral hemorrhage brain. Hypoxic preconditioning also increased neural stem cell secretion of vascular endothelial growth factor. Finally, transplanted neural stem cells with hypoxic preconditioning exhibited enhanced tissue-protective capability that accelerated behavioral recovery. Our results suggest that hypoxic preconditioning in neural stem cells improves efficacy of stem cell therapy for intracerebral hemorrhage.

  8. An in vivo-like tumor stem cell-related glioblastoma in vitro model for drug discovery

    DEFF Research Database (Denmark)

    Jensen, Stine Skov; Aaberg-Jessen, Charlotte; Nørregaard, Annette

    the effects of new drugs on tumor cells including tumor stem cells. Implantation of glioblastoma cells into organotypic brain slice cultures has previously been published as a model system, but not using a stem cell favourable environment. Organotypic corticostriatal rat brain slice cultures were prepared......The discovery of tumor stem cells being highly resistant against therapy makes new demands to model systems suitable for evaluation of the effects of new drugs on tumor stem cells. The aim of the present study was therefore to develop an in vivo-like in vitro glioblastoma model for testing...... and cultured in a serum containing medium replaced after three days with a serum-free stem cell medium. Thereafter fluorescent DiI labelled glioblastoma spheroids from the cell line U87 and the tumor stem cell line SJ-1 established in our laboratory were implanted into the brain slices between cortex...

  9. CD133 Immunohistochemisty in Glioblastoma – Identification of Tumor Stem Cells or a Matter of Coincidence?

    DEFF Research Database (Denmark)

    Hermansen, Simon Kjær; Christensen, Karina Garnier; Jensen, Stine Skov;

    The putative stem cell marker CD133 is the marker of choice for identifying brain tumor stem cells in gliomas, but the use of different antibody clones recognizing different epitopes with different glycosylation status, confuses the field. In this study, we sat out to highlight if current...... suggest that CD133 immunohistochemical studies take this in to consideration by using different CD133 antibody clones together with other stem cell markers and e.g. PCR techniques before too firm conclusions are drawn....

  10. YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Han, Dasol; Byun, Sung-Hyun; Park, Soojeong; Kim, Juwan; Kim, Inhee; Ha, Soobong; Kwon, Mookwang; Yoon, Keejung, E-mail: keejung@skku.edu

    2015-02-27

    Mammalian brain development is regulated by multiple signaling pathways controlling cell proliferation, migration and differentiation. Here we show that YAP/TAZ enhance embryonic neural stem cell characteristics in a cell autonomous fashion using diverse experimental approaches. Introduction of retroviral vectors expressing YAP or TAZ into the mouse embryonic brain induced cell localization in the ventricular zone (VZ), which is the embryonic neural stem cell niche. This change in cell distribution in the cortical layer is due to the increased stemness of infected cells; YAP-expressing cells were colabeled with Sox2, a neural stem cell marker, and YAP/TAZ increased the frequency and size of neurospheres, indicating enhanced self-renewal- and proliferative ability of neural stem cells. These effects appear to be TEA domain family transcription factor (Tead)–dependent; a Tead binding-defective YAP mutant lost the ability to promote neural stem cell characteristics. Consistently, in utero gene transfer of a constitutively active form of Tead2 (Tead2-VP16) recapitulated all the features of YAP/TAZ overexpression, and dominant negative Tead2-EnR resulted in marked cell exit from the VZ toward outer cortical layers. Taken together, these results indicate that the Tead-dependent YAP/TAZ signaling pathway plays important roles in neural stem cell maintenance by enhancing stemness of neural stem cells during mammalian brain development. - Highlights: • Roles of YAP and Tead in vivo during mammalian brain development are clarified. • Expression of YAP promotes embryonic neural stem cell characteristics in vivo in a cell autonomous fashion. • Enhancement of neural stem cell characteristics by YAP depends on Tead. • Transcriptionally active form of Tead alone can recapitulate the effects of YAP. • Transcriptionally repressive form of Tead severely reduces stem cell characteristics.

  11. Stem Cells in Large Animal Models of Retinal and Neurological Disease

    Science.gov (United States)

    2012-01-01

    papers that focus on stem and progenitor cells from the central nervous system (both brain and retina ) of nonrodent mammals, or cells modified to resemble...FEB 2012 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Stem cells in large animal models of retinal and neurological disease...Prescribed by ANSI Std Z39-18 Hindawi Publishing Corporation Stem Cells International Volume 2012, Article ID 460504, 2 pages doi:10.1155/2012/460504

  12. DIFFERENTIATION OF NON-MESENCEPHALIC NEURAL STEM CELLS TOWARDS DOPAMINERGIC NEURONS

    NARCIS (Netherlands)

    Rossler, R.; Boddeke, E.; Copray, S.

    2010-01-01

    Neural stem cells (NSCs), either isolated from fetal or adult human brain or derived from induced pluripotent stem cells, are now considered major candidates for in vitro generation of transplantable dopaminergic (DA) neurons and modeling of Parkinson's disease. It is generally thought that in vitro

  13. Differentiation of mouse embryonic stem cells after transplantation into the adult rat brain%小鼠胚胎干细胞植入大鼠脑内分化的研究

    Institute of Scientific and Technical Information of China (English)

    刘述; 谢瑶; 陈系古; 姚志彬

    2003-01-01

    目的观察小鼠胚胎干 (ES)细胞植人大鼠隔区和海马内后的分化情况 , 并对其作研究和分析.方法成年 SD大鼠 35只,体质量 200~ 250 g,雌雄不限.以 SD大鼠为宿主,将 ES细胞移植入宿主隔区和海马内,移植后 l,2,3,4和 8周后取脑,冷冻切片,进行 Nissl,M6,NSE,GFAP免疫组织化学染色.结果 ES细胞移植入大鼠隔区和海马内后,从第 2周开始表达 M6、 GFAP、 NSE等抗原,持续至第 4周,主要位于移植区内,较少迁移.结论小鼠 ES细胞移植入大鼠隔区和海马内后,分化为神经元,神经胶质细胞.%Aim To observe differentiation of ES cells of mice in adult rat brain after transplantation into septum and hippocampus.Methods 35 adult SD rats weighed 200- 250 g without limitation of sex were used.ES- BALB/C cells were implanted into hippocampus and septum of adult rat,brain was taken at 1st,2nd,3th,4th,8th week.Sections were frozen and Nissl's staining,M6,NSE,GFAP immunohistochemical staining were performed.Results ES grafts expressed M6,GFAP,NSE antigen from second week after implantation into septum and hippocampus which were mainly located in implantation region.Conclusion Transplanted mice ES cells can differentiate into neurons, glia in the septum and hippocampus of rat brain.

  14. Brain radiation - discharge

    Science.gov (United States)

    Radiation - brain - discharge; Cancer-brain radiation; Lymphoma - brain radiation; Leukemia - brain radiation ... Decadron) while you are getting radiation to the brain. It may make you hungrier, cause leg swelling ...

  15. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  16. Brain Basics

    Medline Plus

    Full Text Available ... highly developed area at the front of the brain that, in humans, plays a role in executive functions such as ... Higher Death Rate Among Youth with Psychosis Delayed Walking Link ...

  17. Brain Basics

    Medline Plus

    Full Text Available ... the brain, which is linked to thought and emotion. It is also linked to reward systems in ... or-flight response and is also involved in emotions and memory. anterior cingulate cortex —Is involved in ...

  18. Brain Basics

    Medline Plus

    Full Text Available ... Some people who develop a mental illness may recover completely; others may have repeated episodes of illness ... in early detection, more tailored treatments, and possibly prevention of such illnesses. The Working Brain Neurotransmitters Everything ...

  19. Brain Basics

    Medline Plus

    Full Text Available ... that contains codes to make proteins and other important body chemicals. DNA also includes information to control ... cells required for normal function and plays an important role during early brain development. It may also ...

  20. Brain Basics

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    Full Text Available ... of the cell from its surrounding environment and controls what enters and leaves the cell, and responds ... via axons) to form brain circuits. These circuits control specific body functions such as sleep and speech. ...

  1. Brain Basics

    Medline Plus

    Full Text Available ... in early detection, more tailored treatments, and possibly prevention of such illnesses. The Working Brain Neurotransmitters Everything ... can cause tremors or symptoms found in Parkinson's disease. Serotonin —helps control many functions, such as mood, ...

  2. Brain Basics

    Medline Plus

    Full Text Available ... Offices and Divisions Careers@NIMH Advisory Boards and Groups Staff Directories Getting to NIMH National Institutes of ... electrical signals. The brain begins as a small group of cells in the outer layer of a ...

  3. Brain Basics

    Medline Plus

    Full Text Available ... These circuits control specific body functions such as sleep and speech. The brain continues maturing well into ... factors that can affect our bodies, such as sleep, diet, or stress. These factors may act alone ...

  4. Many facets of stem cells

    Institute of Scientific and Technical Information of China (English)

    Jiarui Wu

    2011-01-01

    @@ Research area on stem cells is one of frontiers in biology.The collection of five research articles in this issue aims to cover timely developments in stem cell biology, ranging from generating and identifying stem cell line to manipulating stem cells, and from basic mechanism analysis to applied medical potential.These papers reflect the various research tasks in stem cell biology.

  5. Global Collaborative STEM Education

    Science.gov (United States)

    Meabh Kelly, Susan; Smith, Walter

    2016-04-01

    Global Collaborative STEM Education, as the name suggests, simultaneously supports two sets of knowledge and skills. The first set is STEM -- science, technology, engineering and math. The other set of content knowledge and skills is that of global collaboration. Successful global partnerships require awareness of one's own culture, the biases embedded within that culture, as well as developing awareness of the collaborators' culture. Workforce skills fostered include open-mindedness, perseverance when faced with obstacles, and resourceful use of technological "bridges" to facilitate and sustain communication. In respect for the 2016 GIFT Workshop focus, Global Collaborative STEM Education projects dedicated to astronomy research will be presented. The projects represent different benchmarks within the Global Collaborative STEM Education continuum, culminating in an astronomy research experience that fully reflects how the global STEM workforce collaborates. To facilitate wider engagement in Global Collaborative STEM Education, project summaries, classroom resources and contact information for established international collaborative astronomy research projects will be disseminated.

  6. Evoked brain potentials and disability in brain-damaged patients.

    Science.gov (United States)

    Rappaport, M; Hall, K; Hopkins, K; Belleza, T; Berrol, S; Reynolds, G

    1977-08-01

    Various measures of evoked brain potential abnormality (EPA) were correlated with disability ratings (DR) for 35 brain-damaged patients. EPA data consisted of judgements of abnormality of ipsilateral, contralateral and bilateral responses to auditory and visual stimuli reflecting activity in the brain stem, subcortex and cortex. DR data were obtained from a scale developed for this study to quantize and categorize patients with a wide range of disabilities from coma to normal functioning. EPA scores based on visual and auditory cortical responses showed significantly positive correlations with degree of disability. Visual response correlation was .49, auditory .38 and combined visual and auditory .51. It was concluded that EPA measures can reflect disability independently of clinical information. They are useful in assessing brain function in general and, specifically, in assessing impairment of sensory function. The evoked potential technique was particularly useful in patients who were not able to participate fully in their own examination. There were indications that the technique may also be valuable in monitoring progress and in predicting clinical outcome in brain-damaged patients.

  7. Reprogramming of adult human neural stem cells into induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    XIE Li-qian; SUN Hua-ping; WANG Tian; TANG Hai-liang; WANG Pu; ZHU Jian-hong; YAO Zheng-wei

    2013-01-01

    Background Since an effective method for generating induced pluripotent stem cells (iPSCs) from human neural stem cells (hNSCs) can offer us a promising tool for studying brain diseases,here we reported direct reprogramming of adult hNSCs into iPSCs by retroviral transduction of four defined factors.Methods NSCs were successfully isolated and cultured from the hippocampus tissue of epilepsy patients.When combined with four factors (OCT3/4,SOX2,KLF4,and c-MYC),iPSCs colonies were successfully obtained.Results Morphological characterization and specific genetic expression confirmed that these hNSCs-derived iPSCs showed embryonic stem cells-like properties,which include the ability to differentiate into all three germ layers both in vitro and in vivo.Conclusion Our method would be useful for generating human iPSCs from NSCs and provide an important tool for studying neurological diseases.

  8. 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.

  9. STEM CELLS AND PROTEOMICS

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yong-ming; GUO Tian-nan; HUANG Shi-ang

    2006-01-01

    The distinctive features of proteomics are large-scale and high throughput. The key techniques of proteomics are two-dimensional gel electrophoresis, mass spectrometry and bioinformatics. Stem cell can differentiate into all kinds of cells, tissues and organs. There are many proteins and cytokines involved in the process of differentiation. Applying proteomics techniques to the research of the complex process of stem cell differentiation is of great importance to study the mechanism and applications of stem cell differentiation.

  10. Cancer stem cells and metastasis.

    Science.gov (United States)

    Sampieri, Katia; Fodde, Riccardo

    2012-06-01

    Cancer stem cells (CSCs) represent a subpopulation of tumour cells endowed with self-renewal and multi-lineage differentiation capacity but also with an innate resistance to cytotoxic agents, a feature likely to pose major clinical challenges towards the complete eradication of minimal residual disease in cancer patients. Operationally, CSCs are defined by their tumour-propagating ability when serially transplanted into immune-compromised mice and by their capacity to fully recapitulate the original heterogeneity of cell types observed in the primary lesions they are derived from. CSCs were first identified in haematopoietic malignancies and later in a broad spectrum of solid tumours including those of the breast, colon and brain. Notably, several CSC characteristics are relevant to metastasis, such as motility, invasiveness and, as mentioned above, resistance to DNA damage-induced apoptosis. Here, we have reviewed the current literature on the relation between CSCs and metastasis formation. Preliminary studies on cancer cell lines and patient-derived material suggest a rate-limiting role for stem-like cells in the processes of tumour cell dissemination and metastasis formation. However, additional studies are needed to deliver formal proof of their identity as the cell of origin of recurrences at distant organ sites. Nevertheless, several studies have already provided pre-clinical evidence of the efficacy of novel therapies directed against disseminated CSCs.

  11. From stem cell to astrocyte: Decoding the regulation of GFAP

    NARCIS (Netherlands)

    R. Kanski

    2014-01-01

    The research presented in this thesis focuses on glial fibrillary acidic protein (GFAP), the main intermediate filament (IF) in astrocytes and astrocyte subpopulations such as neural stem cells (NSCs). In neurodegenerative diseases or upon brain damage, astrocytes respond to an injury with an upregu

  12. Differentiation of neuroepithelia from human embryonic stem cells

    OpenAIRE

    2009-01-01

    We describe the method for in vitro differentiation of neuroepithelial cells from human embryonic stem cells under a chemically defined condition. The protocol is established following the fundamental principle of in vivo neuroectodermal specification. The primitive neuroepithelial cells generated by this protocol can be further induced into neuronal and glia cells with forebrain, mid/hind brain, and spinal cord identities.

  13. Stem Cell Transplants (For Teens)

    Science.gov (United States)

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Stem Cell Transplants KidsHealth > For Teens > Stem Cell Transplants Print ... Does it Take to Recover? Coping What Are Stem Cells? As you probably remember from biology class, every ...

  14. Signaling pathways in self-renewing hematopoietic and leukemic stem cells : do all stem cells need a niche?

    NARCIS (Netherlands)

    Rizo, Aleksandra; Vellenga, Edo; de Haan, Gerald; Schuringa, Jan Jacob

    2006-01-01

    Many adult tissue stem cells, such as the cells of the hematopoietic system, gastrointestinal epithelium, brain, epidermis, mammary gland and lung have now been identified, all of them fulfilling a crucial role in supplying organisms with mature cells during normal homeostasis as well as in times of

  15. Angiogenesis-independent tumor growth mediated by stem-like cancer cells.

    NARCIS (Netherlands)

    Sakariassen, P.; Prestegarden, L.; Wang, J.; Skaftnesmo, K.O.; Mahesparan, R.; Molthoff, C.F.M.; Sminia, P.; Sundlisaeter, E.; Misra, A.; Tysnes, B.B.; Chekenya, M.; Peters, H.; Lende, G.; Kalland, K.H.; Oyan, A.M.; Petersen, K.; Jonassen, I.; Kogel, A.J. van der; Feuerstein, B.G.; Terzis, A.J.; Bjerkvig, R.; Enger, P.O.

    2006-01-01

    In this work, highly infiltrative brain tumors with a stem-like phenotype were established by xenotransplantation of human brain tumors in immunodeficient nude rats. These tumors coopted the host vasculature and presented as an aggressive disease without signs of angiogenesis. The malignant cells ex

  16. Brain death.

    Science.gov (United States)

    Wijdicks, Eelco F M

    2013-01-01

    The diagnosis of brain death should be based on a simple premise. If every possible confounder has been excluded and all possible treatments have been tried or considered, irreversible loss of brain function is clinically recognized as the absence of brainstem reflexes, verified apnea, loss of vascular tone, invariant heart rate, and, eventually, cardiac standstill. This condition cannot be reversed - not even partly - by medical or surgical intervention, and thus is final. Many countries in the world have introduced laws that acknowledge that a patient can be declared brain-dead by neurologic standards. The U.S. law differs substantially from all other brain death legislation in the world because the U.S. law does not spell out details of the neurologic examination. Evidence-based practice guidelines serve as a standard. In this chapter, I discuss the history of development of the criteria, the current clinical examination, and some of the ethical and legal issues that have emerged. Generally, the concept of brain death has been accepted by all major religions. But patients' families may have different ideas and are mostly influenced by cultural attitudes, traditional customs, and personal beliefs. Suggestions are offered to support these families.

  17. Two major gate-keepers in the self-renewal of neural stem cells: Erk1/2 and PLCγ1 in FGFR signaling

    Directory of Open Access Journals (Sweden)

    Lee Jin-A

    2009-06-01

    Full Text Available Abstract Neural stem cells are undifferentiated precursor cells that proliferate, self-renew, and give rise to neuronal and glial lineages. Understanding the molecular mechanisms underlying their self-renewal is an important aspect in neural stem cell biology. The regulation mechanisms governing self-renewal of neural stem cells and the signaling pathways responsible for the proliferation and maintenance of adult stem cells remain largely unknown. In this issue of Molecular Brain [Ma DK et al. Molecular genetic analysis of FGFR1 signaling reveals distinct roles of MAPK and PLCγ1 activation for self-renewal of adult neural stem cells. Molecular Brain 2009, 2:16], characterized the different roles of MAPK and PLCγ1 in FGFR1 signaling in the self-renewal of neural stem cells. These novel findings provide insights into basic neural stem cell biology and clinical applications of potential stem-cell-based therapy.

  18. Investigating Preservice STEM Teacher Conceptions of STEM Education

    Science.gov (United States)

    Radloff, Jeff; Guzey, Selcen

    2016-10-01

    Surrounding the national emphasis on improving STEM education, effective STEM educators are required. Connected, yet often overlooked, is the need for effective preservice STEM teaching instruction for incoming educators. At a basic level, preservice STEM teacher education should include STEM content, pedagogy, and conceptualization. However, the literature suggests no leading conception of STEM education, and little is known about how preservice STEM teachers are conceptualizing STEM education. In order to explore preservice STEM teacher conceptions of STEM education, preservice teachers at a large, Midwestern research university were given an open-ended survey eliciting both textual and visual responses. Here, we report and discuss the results of employing this instrument in relation with the current STEM conceptualization literature.

  19. Immunology of Stem Cells and Cancer Stem Cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-Feng Yang

    2007-01-01

    The capacity of pluri-potent stem cells to repair the tissues in which stem cells reside holds great promise in development of novel cell replacement therapeutics for treating chronic and degenerative diseases. However,numerous reports show that stem cell therapy, even in an autologous setting, triggers lymphocyte infiltration and inflammation. Therefore, an important question to be answered is how the host immune system responds to engrafted autologous stem cells or allogeneous stem cells. In this brief review, we summarize the progress in several related areas in this field, including some of our data, in four sections: (1) immunogenicity of stem cells; (2)strategies to inhibit immune rejection to allograft stem cells; (3) immune responses to cancer stem cells; and (4)mesenchymal stem cells in immune regulation. Improvement of our understanding on these and other aspects of immune system-stem cell interplay would greatly facilitate the development of stem cell-based therapeutics for regenerative purposes.

  20. Dazlin' pluripotent stem cells

    NARCIS (Netherlands)

    Welling, M.A.

    2014-01-01

    Pluripotent embryonic stem cells (ESCs) can be isolated from the inner cell mass (ICM) of blastocyst embryos and differentiate into all three germ layers in vitro. However, despite their similar origin, mouse embryonic stem cells represent a more naïve ICM-like pluripotent state whereas human embryo

  1. Stem cells in dermatology.

    Science.gov (United States)

    Ogliari, Karolyn Sassi; Marinowic, Daniel; Brum, Dario Eduardo; Loth, Fabrizio

    2014-01-01

    Preclinical and clinical research have shown that stem cell therapy could be a promising therapeutic option for many diseases in which current medical treatments do not achieve satisfying results or cure. This article describes stem cells sources and their therapeutic applications in dermatology today.

  2. Making STEM Connections

    Science.gov (United States)

    Stump, Sheryl L.; Bryan, Joel A.; McConnell, Tom J.

    2016-01-01

    Integrated approaches to education in science, technology, engineering, and mathematics (STEM), especially those set in the context of real-world situations, can motivate and deepen students' learning of the STEM subjects (National Academy of Engineering and National Research Council 2014). This article describes two integrated investigations used…

  3. Stem cells in urology.

    Science.gov (United States)

    Aboushwareb, Tamer; Atala, Anthony

    2008-11-01

    The shortage of donors for organ transplantation has stimulated research on stem cells as a potential resource for cell-based therapy in all human tissues. Stem cells have been used for regenerative medicine applications in many organ systems, including the genitourinary system. The potential applications for stem cell therapy have, however, been restricted by the ethical issues associated with embryonic stem cell research. Instead, scientists have explored other cell sources, including progenitor and stem cells derived from adult tissues and stem cells derived from the amniotic fluid and placenta. In addition, novel techniques for generating stem cells in the laboratory are being developed. These techniques include somatic cell nuclear transfer, in which the nucleus of an adult somatic cell is placed into an oocyte, and reprogramming of adult cells to induce stem-cell-like behavior. Such techniques are now being used in tissue engineering applications, and some of the most successful experiments have been in the field of urology. Techniques to regenerate bladder tissue have reached the clinic, and exciting progress is being made in other areas, such as regeneration of the kidney and urethra. Cell therapy as a treatment for incontinence and infertility might soon become a reality. Physicians should be optimistic that regenerative medicine and tissue engineering will one day provide mainstream treatment options for urologic disorders.

  4. Aneuploidy in stem cells

    NARCIS (Netherlands)

    Garcia-Martinez, Jorge; Bakker, Bjorn; Schukken, Klaske M; Simon, Judith E; Foijer, Floris

    2016-01-01

    Stem cells hold enormous promise for regenerative medicine as well as for engineering of model systems to study diseases and develop new drugs. The discovery of protocols that allow for generating induced pluripotent stem cells (IPSCs) from somatic cells has brought this promise steps closer to real

  5. Brain computer

    Directory of Open Access Journals (Sweden)

    Sarah N. Abdulkader

    2015-07-01

    Full Text Available Brain computer interface technology represents a highly growing field of research with application systems. Its contributions in medical fields range from prevention to neuronal rehabilitation for serious injuries. Mind reading and remote communication have their unique fingerprint in numerous fields such as educational, self-regulation, production, marketing, security as well as games and entertainment. It creates a mutual understanding between users and the surrounding systems. This paper shows the application areas that could benefit from brain waves in facilitating or achieving their goals. We also discuss major usability and technical challenges that face brain signals utilization in various components of BCI system. Different solutions that aim to limit and decrease their effects have also been reviewed.

  6. Prominin-1 (CD133 defines both stem and non-stem cell populations in CNS development and gliomas.

    Directory of Open Access Journals (Sweden)

    Karl Holmberg Olausson

    Full Text Available Prominin-1 (CD133 is a commonly used cancer stem cell marker in central nervous system (CNS tumors including glioblastoma (GBM. Expression of Prom1 in cancer is thought to parallel expression and function in normal stem cells. Using RNA in situ hybridization and antibody tools capable of detecting multiple isoforms of Prom1, we find evidence for two distinct Prom1 cell populations in mouse brain. Prom1 RNA is first expressed in stem/progenitor cells of the ventricular zone in embryonic brain. Conversely, in adult mouse brain Prom1 RNA is low in SVZ/SGZ stem cell zones but high in a rare but widely distributed cell population (Prom1(hi. Lineage marker analysis reveals Prom1(hi cells are Olig2+Sox2+ glia but Olig1/2 knockout mice lacking oligodendroglia retain Prom1(hi cells. Bromodeoxyuridine labeling identifies Prom1(hi as slow-dividing distributed progenitors distinct from NG2+Olig2+ oligodendrocyte progenitors. In adult human brain, PROM1 cells are rarely positive for OLIG2, but express astroglial markers GFAP and SOX2. Variability of PROM1 expression levels in human GBM and patient-derived xenografts (PDX - from no expression to strong, uniform expression--highlights that PROM1 may not always be associated with or restricted to cancer stem cells. TCGA and PDX data show that high expression of PROM1 correlates with poor overall survival. Within proneural subclass tumors, high PROM1 expression correlates inversely with IDH1 (R132H mutation. These findings support PROM1 as a tumor cell-intrinsic marker related to GBM survival, independent of its stem cell properties, and highlight potentially divergent roles for this protein in normal mouse and human glia.

  7. Mouse neural stem cells cultured in vitro and expressing an exogenous gene

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Neural stem cells are the multipotential, self-re- newing cells in central nerve system, and play an essential role in the development and differentiation of nerve system. Neural stem cells can be used to treat the nerve system diseases, especially, the transplantation of neural stem cells to rescue the degenerated neural cells has become a very promising therapeutic way. We successfully cultured neural stem cells isolated from the brains of embryonic mice in vitro and determined their distribution in the E17 mice brains. The neural stem cells were transfected with adenoviral vector carrying GFP (green fluorescence protein) gene and then highly expressed the exogenous gene. It paves the way for gene therapy of degenerative nerve system diseases.

  8. Adult neural stem cells in the mammalian central nervous system

    Institute of Scientific and Technical Information of China (English)

    Dengke K Ma; Michael A Bonaguidi; Guo-li Ming; Hongjun Song

    2009-01-01

    Neural stem cells (NSCs) are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to continuously generate functional neurons in specific brain regions throughout life. The adult neurogenesis process is subject to dynamic regulation by various physiological, pathological and pharmacological stimuli. Multipotent adult NSCs also appear to be intrinsically plastic, amenable to genetic programing during normal differentiation, and to epigenetic reprograming during de-differentiation into pluripotency. Increasing evidence suggests that adult NSCs significantly contribute to specialized neural functions under physiological and pathological conditions. Fully understanding the biology of adult NSCs will provide crucial insights into both the etiology and potential therapeutic interventions of major brain disorders. Here, we review recent progress on adult NSCs of the mammalian central nervous system, in-cluding topics on their identity, niche, function, plasticity, and emerging roles in cancer and regenerative medicine.

  9. MicroRNAs: regulators of oncogenesis and stemness

    Directory of Open Access Journals (Sweden)

    Papagiannakopoulos Thales

    2008-06-01

    Full Text Available Abstract MicroRNAs (miRNAs are essential post-transcriptional regulators that determine cell identity and fate. Aberrant expression of miRNAs can lead to diseases, including cancer. Expression of many miRNAs in the de-differentiated brain tumor cancer stem cells resembles that of neural stem cells. In this issue of BMC Medicine, Silber et al provide evidence of the expression of such miRNAs and their potential to mediate differentiation in both stem cell populations. In this commentary, we discuss the known functions of miRNAs in cancer and stem cells, their therapeutic potential and how the findings of Silber et al provide insight into the role of miR-124/miR-137 dysregulation in glioblastomas.

  10. Developing neural stem cell-based treatments for neurodegenerative diseases.

    Science.gov (United States)

    Byrne, James A

    2014-05-30

    Owing to the aging of the population, our society now faces an impending wave of age-related neurodegenerative pathologies, the most significant of which is Alzheimer's disease. Currently, no effective therapies for Alzheimer's disease have been developed. However, recent advances in the fields of neural stem cells and human induced pluripotent stem cells now provide us with the first real hope for a cure. The recent discovery by Blurton-Jones and colleagues that neural stem cells can effectively deliver disease-modifying therapeutic proteins throughout the brains of our best rodent models of Alzheimer's disease, combined with recent advances in human nuclear reprogramming, stem cell research, and highly customized genetic engineering, may represent a potentially revolutionary personalized cellular therapeutic approach capable of effectively curing, ameliorating, and/or slowing the progression of Alzheimer's disease.

  11. PET molecular imaging in stem cell therapy for neurological diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiachuan; Zhang, Hong [Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Nuclear Medicine, Hangzhou, Zhejiang (China); Zhejiang University, Medical PET Center, Hangzhou (China); Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou (China); Tian, Mei [University of Texas, M.D. Anderson Cancer Center, Department of Experimental Diagnostic Imaging, Houston, TX (United States)

    2011-10-15

    Human neurological diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal cord injury and multiple sclerosis are caused by loss of different types of neurons and glial cells in the brain and spinal cord. At present, there are no effective therapies against these disorders. Discovery of the therapeutic potential of stem cells offers new strategies for the treatment of neurological diseases. Direct assessment of stem cells' survival, interaction with the host and impact on neuronal functions after transplantation requires advanced in vivo imaging techniques. Positron emission tomography (PET) is a potential molecular imaging modality to evaluate the viability and function of transplanted tissue or stem cells in the nervous system. This review focuses on PET molecular imaging in stem cell therapy for neurological diseases. (orig.)

  12. Reversible neural stem cell niche dysfunction in a model of multiple sclerosis

    DEFF Research Database (Denmark)

    Rasmussen, Stine; Imitola, Jaime; Ayuso-Sacido, Angel;

    2011-01-01

    OBJECTIVE: The subventricular zone (SVZ) of the brain constitutes a niche for neural stem and progenitor cells that can initiate repair after central nervous system (CNS) injury. In a relapsing-remitting model of experimental autoimmune encephalomyelitis (EAE), the neural stem cells (NSCs) become...... with minocycline, an inhibitor of microglia activation, increases stem cell proliferation in both naive and EAE animals. Minocycline treatment decreases cortical and periventricular pathology in the chronic phase of EAE, improving the proliferation of Sox2 stem cells and NG2 oligodendrocyte precursors cells...

  13. Blood-brain barrier-supported neurogenesis in healthy and diseased brain.

    Science.gov (United States)

    Pozhilenkova, Elena A; Lopatina, Olga L; Komleva, Yulia K; Salmin, Vladimir V; Salmina, Alla B

    2017-02-14

    Adult neurogenesis is one of the most important mechanisms contributing to brain development, learning, and memory. Alterations in neurogenesis underlie a wide spectrum of brain diseases. Neurogenesis takes place in highly specialized neurogenic niches. The concept of neurogenic niches is becoming widely accepted due to growing evidence of the important role of the microenvironment established in the close vicinity to stem cells in order to provide adequate control of cell proliferation, differentiation, and apoptosis. Neurogenic niches represent the platform for tight integration of neurogenesis and angiogenesis supported by specific properties of cerebral microvessel endothelial cells contributing to establishment of partially compromised blood-brain barrier (BBB) for the adjustment of local conditions to the current metabolic needs of stem and progenitor cells. Here, we review up-to-date data on microvascular dynamics in activity-dependent neurogenesis, specific properties of BBB in neurogenic niches, endothelial-driven mechanisms of clonogenic activity, and future perspectives for reconstructing the neurogenic niches in vitro.

  14. Human embryonic stem cells for neuronal repair.

    Science.gov (United States)

    Ben-Hur, Tamir

    2006-02-01

    Human embryonic stem cells may serve as a potentially endeless source of transplantable cells to treat various neurologic disorders. Accumulating data have shown the therapeutic value of various neural precursor cell types in experimental models of neurologic diseases. Tailoring cell therapy for specific disorders requires the generation of cells that are committed to specific neural lineages. To this end, protocols were recently developed for the derivation of dopaminergic neurons, spinal motor neurons and oligodendrocytes from hESC. These protocols recapitulate normal development in culture conditions. However, a novel concept emerging from these studies is that the beneficial effect of transplanted stem cells is not only via cell replacement in damaged host tissue, but also by trophic and protective effects, as well as by an immunomodulatory effect that down-regulates detrimental brain inflammation.

  15. Therapeutic potential of stem cells in auditory hair cell repair

    Directory of Open Access Journals (Sweden)

    Ryuji Hata

    2009-01-01

    Full Text Available The prevalence of acquired hearing loss is very high. About 10% of the total population and more than one third of the population over 65 years suffer from debilitating hearing loss. The most common type of hearing loss in adults is idiopathic sudden sensorineural hearing loss (ISSHL. In the majority of cases, ISSHL is permanent and typically associated with loss of sensory hair cells in the organ of Corti. Following the loss of sensory hair cells, the auditory neurons undergo secondary degeneration. Sensory hair cells and auditory neurons do not regenerate throughout life, and loss of these cells is irreversible and cumulative. However, recent advances in stem cell biology have gained hope that stem cell therapy comes closer to regenerating sensory hair cells in humans. A major advance in the prospects for the use of stem cells to restore normal hearing comes with the recent discovery that hair cells can be generated ex vivo from embryonic stem (ES cells, adult inner ear stem cells and neural stem cells. Furthermore, there is increasing evidence that stem cells can promote damaged cell repair in part by secreting diffusible molecules such as growth factors. These results suggest that stem-cell-based treatment regimens can be applicable to the damaged inner ear as future clinical applications.Previously we have established an animal model of cochlear ischemia in gerbils and showed progressive hair cell loss up to 4 days after ischemia. Auditory brain stem response (ABR recordings have demonstrated that this gerbil model displays severe deafness just after cochlear ischemia and gradually recovers thereafter. These pathological findings and clinical manifestations are reminiscent of ISSHL in humans. In this study, we have shown the effectiveness of stem cell therapy by using this animal model of ISSHL.

  16. [On plant stem cells and animal stem cells].

    Science.gov (United States)

    You, Yun; Jiang, Chao; Huang, Lu-Qi

    2014-01-01

    A comparison of plant and animal stem cells can highlight core aspects of stem-cell biology. In both kingdoms, stem cells are defined by their clonogenic properties and are maintained by intercellular signals. The signaling molecules are different in plants and animals stem cell niches, but the roles of argonaute and polycomb group proteins suggest that there are some molecular similarities.

  17. Acute, regional inflammatory response after traumatic brain injury: Implications for cellular therapy

    OpenAIRE

    Harting, Matthew T.; jimenez, fernando; Adams, Sasha D.; Mercer, David W.; Cox, Charles S.

    2008-01-01

    While cellular therapy has shown promise in the management of traumatic brain injury (TBI), microenvironment interactions between the intracerebral milieu and therapeutic stem cells are poorly understood. We sought to characterize the acute, regional inflammatory response after TBI.

  18. Silicon Brains

    Science.gov (United States)

    Hoefflinger, Bernd

    Beyond the digital neural networks of Chap. 16, the more radical mapping of brain-like structures and processes into VLSI substrates has been pioneered by Carver Mead more than 30 years ago [1]. The basic idea was to exploit the massive parallelism of such circuits and to create low-power and fault-tolerant information-processing systems. Neuromorphic engineering has recently seen a revival with the availability of deep-submicron CMOS technology, which allows for the construction of very-large-scale mixed-signal systems combining local analog processing in neuronal cells with binary signalling via action potentials. Modern implementations are able to reach the complexity-scale of large functional units of the human brain, and they feature the ability to learn by plasticity mechanisms found in neuroscience. Combined with high-performance programmable logic and elaborate software tools, such systems are currently evolving into user-configurable non-von-Neumann computing systems, which can be used to implement and test novel computational paradigms. The chapter introduces basic properties of biological brains with up to 200 Billion neurons and their 1014 synapses, where action on a synapse takes ˜10 ms and involves an energy of ˜10 fJ. We outline 10x programs on neuromorphic electronic systems in Europe and the USA, which are intended to integrate 108 neurons and 1012 synapses, the level of a cat's brain, in a volume of 1 L and with a power dissipation design an intelligent technical response.

  19. Robot brains

    NARCIS (Netherlands)

    Babuska, R.

    2011-01-01

    The brain hosts complex networks of neurons that are responsible for behavior in humans and animals that we generally call intelligent. I is not easy to give an exact definition of intelligence – for the purpose of this talk it will suffice to say that we refer to intelligence as a collection of cap

  20. Shining Light on the Sprout of Life: Optogenetics Applications in Stem Cell Research and Therapy.

    Science.gov (United States)

    Mirzapour Delavar, Hadi; Karamzadeh, Arezou; Pahlavanneshan, Saghar

    2016-06-01

    Optogenetics is the integration of genetics and optics to achieve gain or loss of function of well-defined events in specific cells of living tissue. As a versatile tool, upon light illumination, it allows fast control of precisely defined events in biological systems from single cell to different parts of whole tissue in freely moving animals. Taking advantage of this method, a multitude of studies have been published to understand brain functions and dysfunctions. Although from the beginning, it has been used to target neurons within the neural networks and to understand how specific neurons contribute to brain function, it gradually has been extended to other fields of biology such as stem cell research and therapy. With a combination of optogenetics and stem cells, new opportunities were opened up in stem cell biology and also its integration in new circuit as a cell-based treatment strategy for more common disorders like neurodegenerative and cardiovascular one. Recently, some studies showed that engineered stem cells expressing exogenous light-activated opsins can be used in stem cell biology including tracking the differentiation of stem cells, functional analysis of embryonic stem cell-derived graft, and testing the functional integration of induced pluripotent stem cell-derived neurons. With the advent of non-invasive approach, such as transcranial excitation or inhibition, optogenetics also holds promise for non-invasive control of engineered stem cell.

  1. Brain tumor - children

    Science.gov (United States)

    ... children; Neuroglioma - children; Oligodendroglioma - children; Meningioma - children; Cancer - brain tumor (children) ... The cause of primary brain tumors is unknown. Primary brain tumors may ... (spread to nearby areas) Cancerous (malignant) Brain tumors ...

  2. Understanding Brain Tumors

    Science.gov (United States)

    ... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

  3. Brain Tumors (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Brain Tumors KidsHealth > For Parents > Brain Tumors Print A ... radiation therapy or chemotherapy, or both. Types of Brain Tumors There are many different types of brain ...

  4. Brain and Nervous System

    Science.gov (United States)

    ... Your 1- to 2-Year-Old Brain and Nervous System KidsHealth > For Parents > Brain and Nervous System Print ... brain is quite the juggler. Anatomy of the Nervous System If you think of the brain as a ...

  5. Fish stem cell cultures.

    Science.gov (United States)

    Hong, Ni; Li, Zhendong; Hong, Yunhan

    2011-04-13

    Stem cells have the potential for self-renewal and differentiation. First stem cell cultures were derived 30 years ago from early developing mouse embryos. These are pluripotent embryonic stem (ES) cells. Efforts towards ES cell derivation have been attempted in other mammalian and non-mammalian species. Work with stem cell culture in fish started 20 years ago. Laboratory fish species, in particular zebrafish and medaka, have been the focus of research towards stem cell cultures. Medaka is the second organism that generated ES cells and the first that gave rise to a spermatogonial stem cell line capable of test-tube sperm production. Most recently, the first haploid stem cells capable of producing whole animals have also been generated from medaka. ES-like cells have been reported also in zebrafish and several marine species. Attempts for germline transmission of ES cell cultures and gene targeting have been reported in zebrafish. Recent years have witnessed the progress in markers and procedures for ES cell characterization. These include the identification of fish homologs/paralogs of mammalian pluripotency genes and parameters for optimal chimera formation. In addition, fish germ cell cultures and transplantation have attracted considerable interest for germline transmission and surrogate production. Haploid ES cell nuclear transfer has proven in medaka the feasibility of semi-cloning as a novel assisted reproductive technology. In this special issue on "Fish Stem Cells and Nuclear Transfer", we will focus our review on medaka to illustrate the current status and perspective of fish stem cells in research and application. We will also mention semi-cloning as a new development to conventional nuclear transfer.

  6. Fish Stem Cell Cultures

    Directory of Open Access Journals (Sweden)

    Ni Hong, Zhendong Li, Yunhan Hong

    2011-01-01

    Full Text Available Stem cells have the potential for self-renewal and differentiation. First stem cell cultures were derived 30 years ago from early developing mouse embryos. These are pluripotent embryonic stem (ES cells. Efforts towards ES cell derivation have been attempted in other mammalian and non-mammalian species. Work with stem cell culture in fish started 20 years ago. Laboratory fish species, in particular zebrafish and medaka, have been the focus of research towards stem cell cultures. Medaka is the second organism that generated ES cells and the first that gave rise to a spermatogonial stem cell line capable of test-tube sperm production. Most recently, the first haploid stem cells capable of producing whole animals have also been generated from medaka. ES-like cells have been reported also in zebrafish and several marine species. Attempts for germline transmission of ES cell cultures and gene targeting have been reported in zebrafish. Recent years have witnessed the progress in markers and procedures for ES cell characterization. These include the identification of fish homologs/paralogs of mammalian pluripotency genes and parameters for optimal chimera formation. In addition, fish germ cell cultures and transplantation have attracted considerable interest for germline transmission and surrogate production. Haploid ES cell nuclear transfer has proven in medaka the feasibility of semi-cloning as a novel assisted reproductive technology. In this special issue on “Fish Stem Cells and Nuclear Transfer”, we will focus our review on medaka to illustrate the current status and perspective of fish stem cells in research and application. We will also mention semi-cloning as a new development to conventional nuclear transfer.

  7. Dental pulp stem cells

    DEFF Research Database (Denmark)

    Ashri, N. Y.; Ajlan, S. A.; Aldahmash, Abdullah M.

    2015-01-01

    scaffold, and guided through signaling molecules. Dental pulp stem cells have been used in an increasing number of studies in dental tissue engineering. Those cells show mesenchymal (stromal) stem cell-like properties including self-renewal and multilineage differentiation potentials, aside from...... an updated review on dental pulp stem cells and their applications in periodontal regeneration, in combination with different scaffolds and growth factors.......Inflammatory periodontal disease is a major cause of loss of tooth-supporting structures. Novel approaches for regeneration of periodontal apparatus is an area of intensive research. Periodontal tissue engineering implies the use of appropriate regenerative cells, delivered through a suitable...

  8. Brain computer interfaces, a review.

    Science.gov (United States)

    Nicolas-Alonso, Luis Fernando; Gomez-Gil, Jaime

    2012-01-01

    A brain-computer interface (BCI) is a hardware and software communications system that permits cerebral activity alone to control computers or external devices. The immediate goal of BCI research is to provide communications capabilities to severely disabled people who are totally paralyzed or 'locked in' by neurological neuromuscular disorders, such as amyotrophic lateral sclerosis, brain stem stroke, or spinal cord injury. Here, we review the state-of-the-art of BCIs, looking at the different steps that form a standard BCI: signal acquisition, preprocessing or signal enhancement, feature extraction, classification and the control interface. We discuss their advantages, drawbacks, and latest advances, and we survey the numerous technologies reported in the scientific literature to design each step of a BCI. First, the review examines the neuroimaging modalities used in the signal acquisition step, each of which monitors a different functional brain activity such as electrical, magnetic or metabolic activity. Second, the review discusses different electrophysiological control signals that determine user intentions, which can be detected in brain activity. Third, the review includes some techniques used in the signal enhancement step to deal with the artifacts in the control signals and improve the performance. Fourth, the review studies some mathematic algorithms used in the feature extraction and classification steps which translate the information in the control signals into commands that operate a computer or other device. Finally, the review provides an overview of various BCI applications that control a range of devices.

  9. Brain Computer Interfaces, a Review

    Science.gov (United States)

    Nicolas-Alonso, Luis Fernando; Gomez-Gil, Jaime

    2012-01-01

    A brain-computer interface (BCI) is a hardware and software communications system that permits cerebral activity alone to control computers or external devices. The immediate goal of BCI research is to provide communications capabilities to severely disabled people who are totally paralyzed or ‘locked in’ by neurological neuromuscular disorders, such as amyotrophic lateral sclerosis, brain stem stroke, or spinal cord injury. Here, we review the state-of-the-art of BCIs, looking at the different steps that form a standard BCI: signal acquisition, preprocessing or signal enhancement, feature extraction, classification and the control interface. We discuss their advantages, drawbacks, and latest advances, and we survey the numerous technologies reported in the scientific literature to design each step of a BCI. First, the review examines the neuroimaging modalities used in the signal acquisition step, each of which monitors a different functional brain activity such as electrical, magnetic or metabolic activity. Second, the review discusses different electrophysiological control signals that determine user intentions, which can be detected in brain activity. Third, the review includes some techniques used in the signal enhancement step to deal with the artifacts in the control signals and improve the performance. Fourth, the review studies some mathematic algorithms used in the feature extraction and classification steps which translate the information in the control signals into commands that operate a computer or other device. Finally, the review provides an overview of various BCI applications that control a range of devices. PMID:22438708

  10. Brain Computer Interfaces, a Review

    Directory of Open Access Journals (Sweden)

    Luis Fernando Nicolas-Alonso

    2012-01-01

    Full Text Available A brain-computer interface (BCI is a hardware and software communications system that permits cerebral activity alone to control computers or external devices. The immediate goal of BCI research is to provide communications capabilities to severely disabled people who are totally paralyzed or ‘locked in’ by neurological neuromuscular disorders, such as amyotrophic lateral sclerosis, brain stem stroke, or spinal cord injury. Here, we review the state-of-the-art of BCIs, looking at the different steps that form a standard BCI: signal acquisition, preprocessing or signal enhancement, feature extraction, classification and the control interface. We discuss their advantages, drawbacks, and latest advances, and we survey the numerous technologies reported in the scientific literature to design each step of a BCI. First, the review examines the neuroimaging modalities used in the signal acquisition step, each of which monitors a different functional brain activity such as electrical, magnetic or metabolic activity. Second, the review discusses different electrophysiological control signals that determine user intentions, which can be detected in brain activity. Third, the review includes some techniques used in the signal enhancement step to deal with the artifacts in the control signals and improve the performance. Fourth, the review studies some mathematic algorithms used in the feature extraction and classification steps which translate the information in the control signals into commands that operate a computer or other device. Finally, the review provides an overview of various BCI applications that control a range of devices.

  11. The Creative Brain.

    Science.gov (United States)

    Herrmann, Ned

    1982-01-01

    Outlines the differences between left-brain and right-brain functioning and between left-brain and right-brain dominant individuals, and concludes that creativity uses both halves of the brain. Discusses how both students and curriculum can become more "whole-brained." (Author/JM)

  12. Brain and Addiction

    Science.gov (United States)

    ... Search Term(s): Teens / Drug Facts / Brain and Addiction Brain and Addiction Print Your Brain Your brain is who you are. It’s what ... solve problems, and make decisions. How Does Your Brain Communicate? The brain is a complex communications network ...

  13. Stem Cell Information: Glossary

    Science.gov (United States)

    ... bone, cartilage, stromal cells that support blood formation, fat, and fibrous tissue. Cell-based therapies —Treatment in which stem cells are induced to differentiate into the specific cell type required to repair damaged or destroyed cells or ...

  14. Induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    Siddhartha Bhowmik; LI Yong

    2011-01-01

    Induced pluripotent stem (iPS) cells are a recent development which has brought a promise of great therapeutic values. The previous technique of somatic cell nuclear transfer (SCNT) has been ineffective in humans. Recent discoveries show that human fibroblasts can be reprogrammed by a transient over expression of a small number of genes; they can undergo induced pluripotency. iPS were first produced in 2006. By 2008, work was underway to remove the potential oncogenes from their structure. In 2009, protein iPS (piPS) cells were discovered. Surface markers and reporter genes play an important role in stem cell research. Clinical applications include generation of self renewing stem cells, tissue replacement and many more. Stem cell therapy has the ability to dramatically change the treatment of human diseases.

  15. Innovation and STEM Schools

    Science.gov (United States)

    Roberts, Julia Link

    2015-01-01

    How do schools with a focus on science, technology, engineering, and mathematics (STEM) fit in with state goals to increase innovation and to boost the economy? This article briefly discusses how educators can encourage creativity and innovation.

  16. Endovascular transplantation of stem cells to the injured rat CNS

    Energy Technology Data Exchange (ETDEWEB)

    Lundberg, Johan; Soederman, Mikael; Andersson, Tommy; Holmin, Staffan [Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Department of Neuroradiology, Stockholm (Sweden); Le Blanc, Katarina [Karolinska University Hospital, Department of Stem Cell Research, Karolinska Institutet, Department of Clinical Immunology, Stockholm (Sweden)

    2009-10-15

    Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells. Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p<0.01) and 5 days (p<0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed. Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases. (orig.)

  17. Quantum Brain?

    CERN Document Server

    Mershin, A; Skoulakis, E M C

    2000-01-01

    In order to create a novel model of memory and brain function, we focus our approach on the sub-molecular (electron), molecular (tubulin) and macromolecular (microtubule) components of the neural cytoskeleton. Due to their size and geometry, these systems may be approached using the principles of quantum physics. We identify quantum-physics derived mechanisms conceivably underlying the integrated yet differentiated aspects of memory encoding/recall as well as the molecular basis of the engram. We treat the tubulin molecule as the fundamental computation unit (qubit) in a quantum-computational network that consists of microtubules (MTs), networks of MTs and ultimately entire neurons and neural networks. We derive experimentally testable predictions of our quantum brain hypothesis and perform experiments on these.

  18. Clinical applied value of brain stem auditory evoked potential in facial neuritis patients combined the damage of other cranial nerves%伴其他颅神经症状的面神经炎患者治疗前后的脑干听觉诱发电位研究

    Institute of Scientific and Technical Information of China (English)

    王金风; 王民

    2012-01-01

    Objective: To explore the clinical applied value of brain stem auditoryk evoed potential (BAEP)in facial neuritis patients combined with damage of other cranial nerves. Methods: Fifty facial neuritis patients combined with damage of other cranial nerves were selected to get BAEP information) the results before and after treatment were analyzed. Results;The inter-peak latencies (IPL) of Ⅰ -- Ⅲ, Ⅲ - V . Ⅰ - V were significantly shorten(P<0. 01)after treatment of the. More than one IPL shortened IPL took up 84%. 74% cases had prolonged potential latencies (PL) of Wave I , Ⅲ and V with more than one shortened or disappeared waveform. In 69 % cases with amplitude of wave V increased and ratio of V/ I more than 0. 5 or ILD of bilateral Wave V was less than 0. 3 ms, IPL of Ⅲ - V shorter than that of Ⅰ - Ⅲ. Conclusion:Facial neuritis involves not only medial surface nerves of foramen stylomastoi-deum but also brainstem and/or other cranial nerves . BAEP can objectively reflect the function of audi-tory system and brain stem, and can be used to follow-up with patients with facial neuritis.%目的:观察伴其他颅神经症状的面神经炎患者治疗前后的脑干听觉诱发电位(BAEP)表现.方法:选择50例面神经炎伴其他颅神经症状的患者进行BAEP检测,并进行治疗前后对比.结果:与治疗前相比,治疗后Ⅱ-Ⅲ、Ⅲ-Ⅴ、Ⅰ-Ⅴ波IPL明显缩短(P<0.01),其中有一个以上的IPL缩短者42例占84%;Ⅰ、Ⅲ、Ⅴ波PL有一个以上缩短或治疗前BAEP波形消失而于治疗后出现者37例占74%;Ⅴ波波幅增高并且Ⅴ/Ⅰ IPL比大于0.5或双侧Ⅴ波侧间潜伏期差(IDL)小于0.3 ms,Ⅲ-Ⅴ波IPL小于Ⅰ-Ⅲ波IPL的35例占70%.结论:面神经炎不仅累及茎乳孔内面神经,还可累及脑干和其他颅神经.BAEP可以客观地反映面神经炎患者听觉系统和脑干功能,因此可以用于对该类患者进行疗效观察.

  19. The hematopoietic growth factor "erythropoietin" enhances the therapeutic effect of mesenchymal stem cells in Alzheimer's disease.

    Science.gov (United States)

    Khairallah, M I; Kassem, L A; Yassin, N A; El Din, M A Gamal; Zekri, M; Attia, M

    2014-01-01

    Alzheimer's disease is a neurodegenerative disorder clinically characterized by cognitive dysfunction and by deposition of amyloid plaques, neurofibrillary tangles in the brain. The study investigated the therapeutic effect of combined mesenchymal stem cells and erythropoietin on Alzheimer's disease. Five groups of mice were used: control group, Alzheimer's disease was induced in four groups by a single intraperitoneal injection of 0.8 mg kg(-1) lipopolysaccharide and divided as follows: Alzheimer's disease group, mesenchymal stem cells treated group by injecting mesenchymal stem cells into the tail vein (2 x 10(6) cells), erythropoietin treated group (40 microg kg(-1) b.wt.) injected intraperitoneally 3 times/week for 5 weeks and mesenchymal stem cells and erythropoietin treated group. Locomotor activity and memory were tested using open field and Y-maze. Histological, histochemical, immunohistochemical studies, morphometric measurements were examined in brain sections of all groups. Choline transferase activity, brain derived neurotrophic factor expression and mitochondrial swellings were assessed in cerebral specimens. Lipopolysaccharide decreased locomotor activity, memory, choline transferase activity and brain derived neurotrophic factor. It increased mitochondrial swelling, apoptotic index and amyloid deposition. Combined mesenchymal stem cells and erythropoietin markedly improved all these parameters. This study proved the effective role of mesenchymal stem cells in relieving Alzheimer's disease symptoms and manifestations; it highlighted the important role of erythropoietin in the treatment of Alzheimer's