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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nestin, an intermediate filament protein, is known to be expressed in the proliferating and provisional cells of the developing mammalian brain and is lost during differentiation. The aim of the present study was to determine the morphological type and localization areas of the rat brain cells exhibiting the ability to synthesize nestin after a short-term global ischemia of the brain. Induction of nestin synthesis after a short-term ischemia was found within the injured brain areas in astrocytes, which exhibited structural features atypical for these cells in mature brain and maintained them for a long time, and in the morphologically undifferentiated cells of subventricular zone, which were able to proliferate. However, acquisition by astrocytes of some phenotypic properties of immature glial cell does not by itself support the view that they may transform into neural stem cells.
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PMID:[Ischemic damage-induced nestin synthesis in the rat brain cells]. 1752 58

After neurotrauma, ischemia, or neurodegenerative disease, astrocytes upregulate their expression of the intermediate filament proteins glial fibrillary acidic protein (GFAP), vimentin (Vim), and nestin. This response, reactive gliosis, is attenuated in GFAP(-/-)Vim(-/-) mice, resulting in the promotion of synaptic regeneration after neurotrauma and improved integration of retinal grafts. Here we assessed whether GFAP(-/-)Vim(-/-) astrocytes affect the differentiation of neural progenitor cells. In coculture with GFAP(-/-)Vim(-/-) astrocytes, neural progenitor cells increased neurogenesis by 65% and astrogenesis by 124%. At 35 days after transplantation of neural progenitor cells into the hippocampus, adult GFAP(-/-)Vim(-/-) mice had more transplant-derived neurons and astrocytes than wild-type controls, as well as increased branching of neurite-like processes on transplanted cells. Wnt3 immunoreactivity was readily detected in hippocampal astrocytes in wild-type but not in GFAP(-/-)Vim(-/-) mice. These findings suggest that GFAP(-/-)Vim(-/-) astrocytes allow more neural progenitor cell-derived neurons and astrocytes to survive weeks after transplantation. Thus, reactive gliosis may adversely affect the integration of transplanted neural progenitor cells in the brain. Disclosure of potential conflicts of interest is found at the end of this article.
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PMID:Increased neurogenesis and astrogenesis from neural progenitor cells grafted in the hippocampus of GFAP-/- Vim-/- mice. 1762 17

In this research, we investigated striatal neurogenesis in 3-, 6-, 12-, and 18-month-old rats after cerebral ischemic injury. All rats were subjected to a 20-min middle cerebral artery occlusion (MCAO), given 5'-bromodeoxyuridine (BrdU, 30 mg/kg, i.p.) once daily during days 4-7 and sacrificed 2 weeks after MCAO. Neurogenesis was assessed with double immunohistochemical/immunofluorescence labeling of BrdU and doublecortin (DCX), microtubule-associated protein 2 (MAP-2), or 67-kDa glutamic acid decarboxylase (GAD(67)). In 6-, 12-, and 18-month-old rats, the numbers of nestin(+), BrdU(+)-DCX(+) (a marker of newborn neuronal progenitors/immature neuron), BrdU(+)-MAP-2(+) (a marker of newborn mature neuron), and BrdU(+)-GAD(67)(+) (a marker of newborn GABAergic neuron) cells decreased dramatically in the ipsilateral striatum to MCAO compared with that in 3-month-old rats. The results indicated that stroke-induced striatal neurogenesis still existed in aging rats. However, the capacity of neurogenesis in older rats was considerably lower than that in young adults. Meanwhile, the apoptosis of neural precursors and immature neurons, indicated by double labeling of active caspase-3 and nestin/DCX/Tuj-1(beta-tubulin III)/CRMP-4 (collapsin response-mediated protein-4), increased noticeably in the ipsilateral striatum of older rats. Taken together, the results suggested that aging-related attenuation of ischemia-induced striatal neurogenesis might be related to decrease of neural precursors and increase of apoptosis of newborn neurons.
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PMID:Age-related decrease of striatal neurogenesis is associated with apoptosis of neural precursors and newborn neurons in rat brain after ischemia. 1766

In neurotrauma, brain ischemia or neurodegenerative diseases, astrocytes become reactive (which is known as reactive gliosis) and this is accompanied by an altered expression of many genes. Two cellular hallmarks of reactive gliosis are hypertrophy of astrocyte processes and the upregulation of the part of the cytoskeleton known as intermediate filaments, which are composed of nestin, vimentin, and GFAP. Our aim has been to better understand the function of reactive astrocytes in CNS diseases. Using mice deficient for astrocyte intermediate filaments (GFAP(-/-)Vim(-/-)), we were able to attenuate reactive gliosis and slow down the healing process after neurotrauma. We demonstrated the key role of reactive astrocytes in neurotrauma-at an early stage after neurotrauma, reactive astrocytes have a neuroprotective effect; at a later stage, they facilitate the formation of posttraumatic glial scars and inhibit CNS regeneration, specifically, they seem to compromise neural graft survival and integration, reduce the extent of synaptic regeneration, inhibit neurogenesis in the old age, and inhibit regeneration of severed CNS axons. We propose that reactive astrocytes are the future target for the therapeutic strategies promoting regeneration and plasticity in the brain and spinal cord in various disease conditions. Through its involvement in inflammation, opsonization, and cytolysis, complement protects against infectious agents. Although most of the complement proteins are synthesized in CNS, the role of the complement system in the normal or ischemic CNS remains unclear. Complement activiation in the CNS has been generally considered as contributing to tissue damage. However, growing body of evidence suggests that complement may be a physiological neuroprotective mechanism as well as it may participate in maintenance and repair of the adult brain.
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PMID:The role of astrocytes and complement system in neural plasticity. 1767 57

Neural progenitor cells (NPCs) in the subventricular zone (SVZ) travel a long distance along the rostral migratory stream (RMS) to give rise to interneurons in the olfactory bulb (OB). Using the multiphoton microscope and time-lapse recording techniques we here report the behavior of NPCs in the RMS under both intact and ischemic conditions in living brain slices. The NPCs were visualized in 3-week-old transgenic mice that carry the reporter gene, green fluorescent protein (GFP), driven by the nestin promoter. Cortical brain ischemia was induced by permanent occlusion of the right common carotid artery and the middle cerebral artery. We observed that the RMS contained two populations of NPCs: nonmigrating cells (bridge cells) and migrating cells. Bridge cells enabled migrating cells to travel and also produced new cells in the RMS. The direction of NPC migration in the RMS was bidirectional in both intact and ischemic conditions. Cortical ischemia impeded NPC travel in the RMS next to the lesion area during the early period of ischemia. Cell-cell contact was a prominent feature affecting NPC translocation and migratory direction. These data suggest that behavior and function of nestin-positive NPCs in the RMS are variable. Cell-cell contacts and microenvironmental changes influence NPC behavior in the RMS. This study may provide insights to help in understanding NPC biology.
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PMID:Multiphoton microscope imaging: the behavior of neural progenitor cells in the rostral migratory stream. 1772 76

Hyperbaric oxygen therapy promoted brain cell proliferation. Wnt-3 is closely associated with the proliferation of neural stem cells. We examined whether hyperbaric oxygen promoted neural stem cells to proliferate and its correlation with Wnt-3 protein in hypoxic-ischemic neonate rats. Hyperbaric oxygen therapy was administered 3 h after hypoxia ischemia daily for 7 days. The proliferating stem cells and Wnt-3 protein were examined dynamically in the subventricular zone. Results showed that stem cells proliferated and peaked 7 days after hyperbaric oxygen therapy. Wnt-3 protein increased to the higher levels 3 days after therapy. Linear regression analysis showed that nestin protein correlated with Wnt-3 protein. We propose that hyperbaric oxygen treatment promote stem cells to proliferate, which is correlated with Wnt-3 protein.
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PMID:Proliferation of neural stem cells correlates with Wnt-3 protein in hypoxic-ischemic neonate rats after hyperbaric oxygen therapy. 1792 81

Neurogenesis is nearly completed after birth, whereas gliogenic activities remain intense during the postnatal period in the developing rat cortex. These include involution of radial glia, proliferation of astrocytes and oligodendrocytes and myelin formation. Little is known about the effects of hypoxic-ischemic (HI) injury on these critical postnatal processes. Here we explored the glial reactions to mild HI injury of the neonatal rat cerebral cortex at P3. We show that the HI lesion results in disruption of the normal radial glia architecture, which was paralleled by an increase in GFAP immunopositive reactive astrocytes. The morphology of these latter cells and the fact that they were immunolabelled for both nestin and GFAP suggest an accelerated transformation of radial glia into astrocytes. In addition, BrdU/GFAP immunostaining revealed a significant increase of double-labelled cells indicating an acute proliferation of astrocytes after HI. This enhanced proliferative activity of astrocytes persisted for several weeks. We found an elevated number and increased mitotic activity of both NG2-positive oligodendrocyte progenitors and RIP-positive oligodendrocytes after injury. These findings imply that glial responses are central to cortical tissue remodelling following neonatal ischemia and represent a potential target for therapeutic approaches.
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PMID:Glial responses to neonatal hypoxic-ischemic injury in the rat cerebral cortex. 1794 66

Glial cell line-derived neurotrophic growth factor (GDNF), a member of the transforming growth factor family, is necessary for renal organogenesis and exhibits changes in expression in models of renal disease. Nestin is an intermediate filament protein originally believed to be a marker of neuroepithelial stem cells and recently proposed as a marker of mesenchymal stem cells (MSC). Having demonstrated the participation of nestin-expressing cells in renoprotection during acute renal ischemia, we hypothesized that growth factors and transcription factors similar to those operating in the nervous system should be also operant in the kidney and may be induced after noxious stimuli, such as an ischemic episode. Using cultured kidney-derived MSC, which abundantly express nestin, we confirmed expression of GDNF by these cells and demonstrated the GDNF-induced expression of GDNF. The cellular expression of nestin paralleled that of GDNF: serum starvation decreased the expression, whereas application of GDNF resulted in a dose-dependent increase in nestin expression. Immunohistochemical and Western blot analyses of kidneys obtained from control and postischemic mice showed that expression of GDNF was much enhanced in the renal cortex, a pattern similar to the previously reported expression of nestin. Based on the observed GDNF-induced GDNF expression, we next explored the effect of supplemental GDNF administered early after ischemia on renal function postischemia. GDNF-treated mice were protected against acute ischemia. To address potential mechanisms of the observed renoprotection, in vitro studies showed that GDNF accelerated MSC migration in a wound-healing assay. Hypoxia did not accelerate, but rather slightly reduced, the motility of MSC and reduced the expression of GDNF in MSC by approximately twofold. Furthermore, GDNF was cytoprotective against oxidative stress-induced apoptotic death of MSC. Collectively, these data establish 1) an autoregulatory circuit of GDNF-induced GDNF expression in renal MSC; 2) induction of GDNF expression in postischemic kidneys; 3) the ability of exogenous GDNF to ameliorate ischemic renal injury; and 4) a possible contribution of GDNF-induced motility and improved survival of MSC to renoprotection.
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PMID:Glial cell line-derived neurotrophic growth factor increases motility and survival of cultured mesenchymal stem cells and ameliorates acute kidney injury. 1800 56

The goal of this work was to study changes structural and cytochemical organization of rat hippocampus activated astrocytes after a brief total brain ischemia. By methods of immunocytochemical determination of proteins of intermediate filaments, in was established that 7 days after the ischemia the functional activation of dorsal hippocampus astrocytes is morphologically manifested both as changes of size and shape of the cells and their processes and as accumulation of the intermediate filament proteins -GFAP and nestin. Two populations of the activated astrocytes are formed - more dispersed GFAP-positive astrocytes and nestin-positive astrocytes located predominantly in the area of massive death of nerve cells. The obtained data allow suggesting that the postischemic activation of astrocytes is accompanied by their acquistition of properties characteristic of immature cells of the nervous tissue; however, the absence of morphological signs of dedifferentiation does not permit these cells to be considered responsible for reparational neurogenesis in hippocampus.
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PMID:[Morphological manifestations of astrocyte local functional activation produced by a short-term total brain ischemia]. 1803 40

Human bone marrow contains two major cell types, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). MSCs possess self-renewal capacity and pluripotency defined by their ability to differentiate into osteoblasts, chondrocytes, adipocytes and muscle cells. MSCs are also known to differentiate into neurons and glial cells in vitro, and in vivo following transplantation into the brain of animal models of neurological disorders including ischemia and intracerebral hemorrhage (ICH) stroke. In order to obtain sufficient number and homogeneous population of human MSCs, we have clonally isolated permanent and stable human MSC lines by transfecting primary cell cultures of fetal human bone marrow MSCs with a retroviral vector encoding v-myc gene. One of the cell lines, HM3.B10 (B10), was found to differentiate into neural cell types including neural stem cells, neurons, astrocytes and oligodendrocytes in vitro as shown by expression of genetic markers for neural stem cells (nestin and Musashi1), neurons (neurofilament protein, synapsin and MAP2), astrocytes (glial fibrillary acidic protein, GFAP) and oligodendrocytes (myelin basic protein, MBP) as determined by RT-PCR assay. In addition, B10 cells were found to differentiate into neural cell types as shown by immunocytochical demonstration of nestin (for neural stem cells), neurofilament protein and beta-tubulin III (neurons) GFAP (astrocytes), and galactocerebroside (oligodendrocytes). Following brain transplantation in mouse ICH stroke model, B10 human MSCs integrate into host brain, survive, differentiate into neurons and astrocytes and induce behavioral improvement in the ICH animals. B10 human MSC cell line is not only a useful tool for the studies of organogenesis and specifically for the neurogenesis, but also provides a valuable source of cells for cell therapy studies in animal models of stroke and other neurological disorders.
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PMID:Multilineage potential of stable human mesenchymal stem cell line derived from fetal marrow. 1806 66


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