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

This study addresses whether hippocampal progenitor cells express nestin following cerebral ischemia in rats. Cell counts within the hippocampal hilus were significantly greater following severe (eight-vessel occlusion) ischemia than following intermediate (four-vessel occlusion) ischemia (1527+/-87/mm2 vs. 918+/-71/mm2). Bromedeoxyuridine-positive cell counts were significantly higher with severe ischemia than with intermediate ischemia or in sham-operated animals, respectively (368+/-45, 43+/-14 and 7+/-1/mm2). In the eight-vessel occlusion group, 47+/-8/mm2 bromedeoxyuridine-labeled cells expressed nestin, significantly higher than in the four-vessel occlusion group and sham-operated animals (1+/-1 and 1+/-0/mm2, P<0.01 vs. eight-vessel occlusion, respectively). Confocal microscopy verified that a subset of the bromedeoxyuridine-positive cells expressed nestin. In conclusion, severe ischemia elicits nestin expression in hippocampal progenitor cells in rats.
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PMID:Hippocampal progenitor cells express nestin following cerebral ischemia in rats. 1614 41

Neural stem cells are multipotent progenitor cells that show self-renewal activity. In this study, we assessed the use of neural stem cells for ameliorating ischemia-reperfusion injury of the gerbil cochlea. Neural stem cells were injected into one inner ear through the round window 1 day after ischemic insult. Immunostaining for nestin showed that the distribution of neural stem cells was concentrated within the organ of Corti. Seven days after ischemia, the injury-induced auditory brainstem response threshold shift and progressive inner hair cell damage were markedly less on the neural stem cell-transplanted side. These results suggest that the transplantation of neural stem cells is therapeutically useful for preventing damage to hair cells that occurs after transient ischemia of the cochlea.
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PMID:Neural stem cells suppress the hearing threshold shift caused by cochlear ischemia. 1614 42

An 8-vessel-occlusion (8VO) method was developed to compare with the conventional 4-vessel-occlusion (4VO) in hippocampal ischemic damage and progenitor cell induction 10 days following ischemia in female rats. Eight posture-relevant tests were performed following ischemia to correlate grades of postural abnormality with the histological outcome. The total hippocampal living cell ratio including 7 hippocampal subregions in 8VO group (n=11) was much lower than that in 4VO group (n=10, 51+/-5% vs. 78+/-4, p<0.01). In 4VO group, BrdU positive cells were mainly located in the subgranular zone (SGZ) with a count of 54+/-20/mm2 (7micro-thick slice), comparable to the maximal level following global ischemia in male gerbils and rats reported so far referring to slice-thickness differences (50-60 micro-thick slices). Similarly, nestin-bearing cells were 29+/-11/ mm2. In 8VO group, BrdU and nestin positive cells increased by 10 times. Triple staining of BrdU, nestin and DAPI demonstrated that BrdU-immunoreactivity was extensively distributed in the hippocampal hilus while the nestin was mainly located along the SGZ. Most of nestin labeling was not co-localized with the BrdU, indicating that establishment of these cells might precede BrdU injections (8 and 9d post ischemia). Behavioral scores were much greater for 8VO group than for 4VO group and composite postural scores well correlated with the hippocampal cell loss. In conclusion, severe ischemia correlates with vigorous induction of the hippocampal progenitor cells in rats while behavioral profiling of posture changes permits prediction of severity of damage.
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PMID:Increased severity of acute cerebral ischemic injury correlates with enhanced stem cell induction as well as with predictive behavioral profiling. 1618 Oct 88

Regarding regenerative strategies early post-ischemic therapeutic interventions might have a great impact on further pathophysiological cascades. To understand the early post-ischemic events we analyzed proliferation and neurogenesis as early as on day 3 after transient global ischemia in rats. Evaluations were performed not only in the dorsal hippocampus, where post-ischemic cell death develops selectively in the cornu ammonis, subfield 1 area, but also in distant areas like the ventricle wall and the striatum. Ischemia was induced by a transient two-vessel occlusion combined with hypotension. Animals received daily i.p. injections of 5-bromo-2-deoxyuridine until decapitation 1 or 3 days after ischemia. Immunohistochemistry was performed to detect 5-bromo-2-deoxyuridine and co-labeling with cell-specific markers. Three days after ischemia, proliferation significantly increased throughout the forebrain. Early neurogenesis, detected by doublecortin labeling, on the other hand, was restricted to the neurogenic zones of the dentate gyrus and the lateral ventricle. Global ischemia reduced the overall number of doublecortin-positive cells in the dentate gyrus, particularly in the upper blade of the dentate gyrus. However, the number of newly generated doublecortin- and 5-bromo-2-deoxyuridine double-labeled cells was unchanged. The vast majority of newly generated cells were microglia/macrophages, which invaded morphologically damaged as well as undamaged regions. Astroglial cells were activated all over the forebrain by the ischemic insult. They were co-localized almost completely with nestin in many areas, yet, sparsely proliferated after the insult. Interestingly, in locally defined zones we found nestin- and glial fibrillary acidic protein-signals clearly separated. In sham-operated animals, nestin could be detected in both neurogenic zones only without co-labeling with glial markers. In conclusion, during the first days after global ischemia, cell death of cornu ammonis, subfield 1-neurons was accompanied by a massive overall proliferation and activation of microglia/macrophages, a reduction of pre-ischemia existing doublecortin-positive precursors in the dentate gyrus and a re-expression of nestin in glial fibrillary acidic protein-positive astrocytes.
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PMID:Increase in proliferation and gliogenesis but decrease of early neurogenesis in the rat forebrain shortly after transient global ischemia. 1621 27

Previous reports have indicated that the expression of bone morphogenetic protein-7 (BMP7) is enhanced after ischemic injury in brain. This upregulation may induce endogenous neurorepair in the ischemic brain. The purpose of this study was to examine neuroregenerative effects of BMP7 after ischemia-reperfusion injury. Adult Sprague-Dawley rats were anesthetized with chloral hydrate. Right middle cerebral artery (MCA) was transiently ligated with 10-O suture for 1 h. One day after MCA occlusion, vehicle or BMP7 was infused to the contralateral cerebral ventricle. To identify possible neurogenesis, bromodeoxyurindine (BrdU) was systemically injected on the fourth and fifth days after MCA occlusion. Animals treated with BMP7 showed a rapid correction of body asymmetry and neurological deficits, suggesting BMP7 facilitates recovery after stroke. Animals were sacrificed at 1 month after stroke and brains were analyzed using immunohistological techniques. BMP7 treatment enhanced immunoreactivity of BrdU in the subventricular zone, lesioned cortex, and corpus callosum. These BrdU-positive cells co-labeled with nestin and NeuN. Our behavioral and anatomical data suggest that BMP7 promotes neuroregeneration in stroke animals, possibly through the proliferation of new neuronal precursors after ischemia.
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PMID:Neuroregenerative effects of BMP7 after stroke in rats. 1623 21

Cerebral ischemia evokes changes in gene expression time-dependently after the ischemic event. Most studies on transcriptional changes following ischemia have centered on relatively early postischemic time points, and detected multiple genes relevant to neuronal cell death. However, functional outcome after ischemia depends critically on adaptations of the postischemic brain. Plasticity may derive from network-inherent changes, or from the formation of new nerve cells in the CNS. We have screened for gene expression changes up to 3 weeks following a limited photothrombotic cortical insult in the rat sensorimotor cortex by using the sensitive restriction-mediated differential display (RMDD) technique. A high number of genes were detected as induced at early or intermediate time points in the ipsi- and contralateral cortex (6 and 48 h). Unexpectedly, at the late time point examined (3 weeks), we still detected 40 genes that were changed in their expression. We further characterized the expression of two genes linked to neurogenesis (nestin and stathmin), and two genes likely involved in reconfiguring neuronal networks (semaphorin VIa and synaptotagmin IV). Conclusively, our data highlight the degree of long-term transcriptional changes in the cortex after ischemia, and provide insight into functional pathways of relevance for compensatory recovery mechanisms in neural networks.
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PMID:Long-term gene expression changes in the cortex following cortical ischemia revealed by transcriptional profiling. 1653 Jan 83

Perinatal hypoxia/ischemia (H/I) is the leading cause of neurologic injury resulting from birth complications. Recent advances in critical care have dramatically improved the survival rate of infants suffering this insult, but approximately 50% of survivors will develop neurologic sequelae such as cerebral palsy, epilepsy or cognitive deficits. Here we demonstrate that tripotential neural stem/progenitor cells (NSPs) participate in the regenerative response to perinatal H/I as their numbers increase 100% by 3 d and that they alter their intrinsic properties to divide using expansive symmetrical cell divisions. We further show that production of new striatal neurons follows the expansion of NSPs. Increased proliferation within the NSP niche occurs at 2 d after perinatal H/I, and the proliferating cells express nestin. Of those stem-cell related genes that change, the membrane receptors Notch1, gp-130, and the epidermal growth factor receptor, as well as the downstream transcription factor Hes5, which stimulate NSP proliferation and regulate stem cellness are induced before NSP expansion. The mechanisms for the reactive expansion of the NSPs reported here reveal potential therapeutic targets that could be exploited to amplify this response, thus enabling endogenous precursors to restore a normal pattern of brain development after perinatal H/I.
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PMID:Neural stem/progenitor cells participate in the regenerative response to perinatal hypoxia/ischemia. 1662 56

The standard method of detecting neurogenesis uses bromodeoxyuridine (BrdU) to label DNA synthesis followed by double labeling with neuronal markers. However, DNA synthesis may occur in events unrelated to neurogenesis including aneuploidy and abortive cell cycle reentry. Hence, it is important to confirm neurogenesis with methods other than BrdU incorporation. To this end, we have generated transgenic nestin-CreER mice that express tamoxifen-inducible Cre recombinase under the control of a nestin enhancer. When crossed with a ubiquitous Enhanced Green Fluorescent Protein (EGFP)-Cre-reporter line, the bitransgenic animals can reveal the nestin-positive progenitors and their progeny with EGFP after tamoxifen induction. This system has many applications including visualization of embryonic neural progenitors, detection of postnatally transformed radial glial cells, and labeling adult neural progenitors in the subventricular zone (SVZ). To examine the contribution of SVZ progenitors to cell replacement after stroke, tamoxifen-induced mice were challenged with focal ischemia or combined ischemia-hypoxia followed by BrdU injection. This analysis revealed only very few EGFP-positive cells outside the SVZ after focal ischemia but robust DNA synthesis by hippocampal neurons without immediate cell death following ischemia-hypoxia. These results suggest that the nestin-CreER system is a useful tool for detecting embryonic and adult neurogensis. They also confirm the existence of nonproliferative DNA synthesis by old neurons after experimental brain injury.
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PMID:Nestin-CreER mice reveal DNA synthesis by nonapoptotic neurons following cerebral ischemia hypoxia. 1725 45

Old age is associated with an enhanced susceptibility to stroke and poor recovery from brain injury, but the cellular mechanisms underlying such phenomena are not known. Using BrdU-labeling, quantitative immunohistochemistry and 3D-reconstruction of confocal images in a rat model of mild cerebral ischemia, we found that aged rats are highly susceptible to develop an early infarct that is associated with premature cellular proliferation originating from the vascular tree. In aged rats we also found a rapid delimitation of the infarct area by capillary-derived neuroepithelial cells and an early incorporation of these cells into the glial scar. Since most proliferating cells at the infarct site are microglia or nestin-positive cells derived from the vascular wall, we conclude that the vasculature plays a hitherto unrecognized role as a source of proliferating neuroepithelial cells after stroke. Age-associated alterations in the timing and origin of the cytogenic response to cerebral ischemia may underlie the poor functional recovery from stroke. Clarifying the molecular basis of these phenomena could yield novel approaches to enhancing neurorestoration in the elderly. Studies of stroke in experimental animals have demonstrated the neuroprotective efficacy of a variety of interventions, but most of the strategies that have been clinically tested failed to show benefit in aged humans. One possible explanation for this discrepancy between laboratory and clinical investigations is the role that age plays in the recovery of the brain from insult. Although it is well known that aging is a risk factor for stroke (Barnett HJ, 2002), the majority of experimental studies of stroke have been performed on young animals, and therefore may not fully replicate the effects of ischemia on neural tissue in aged subjects (Wang LC et al., 1995; Davies M et al., 1995; Sutherland GR et al., 1996; Popa-Wagner A et al., 1998, 1999a). Hence, the aged post-acute animal model is clinically most relevant to stroke rehabilitation and cellular studies (Lindner MD et al., 2003; Brown AW et al., 2003; Badan I et al., 2003).
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PMID:Premature cellular proliferation following cortical infarct in aged rats. 1730 79

Heparanase is an enzyme that cleaves heparan sulfate proteoglycans, an important component of the extracellular matrix to generate heparan sulfate fragments, leading to the remodeling of the extracellular matrix and the basement membrane particularly during cancer metastasis. A growing body of evidence suggests that heparanase serves multiple functions in normal tissues including the central nervous system. In this study, we showed that heparanase is expressed in reactive astrocytes in the peri-infarct lesion of a rat brain whose middle cerebral artery was transiently occluded for 90 min. RT-PCR and Western blot analyses revealed that heparanase expression was markedly upregulated during the subacute phase of ischemia (from 3 to 7 days post-reperfusion (dpr)). As revealed by immunohistochemical study, heparanase was localized in astrocytes located in the peri-infarct region. Heparanase+ astrocytes expressed nestin that is known as a marker of reactive astrocytes. Infiltrated neutrophils were weakly heparanase+. After 7 dpr, the expression level of heparanase+ astrocytes considerably decreased. Therefore, the maximum expression of heparanase by astrocytes may correlate with the time of migration of reactive astrocytes toward the ischemic core, which may result in astrogliosis. These findings suggest a novel role of heparanase in the pathophysiology of brain ischemia.
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PMID:Expression of heparanase in nestin-positive reactive astrocytes in ischemic lesions of rat brain after transient middle cerebral artery occlusion. 1736 23


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