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

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

Ischemia-induced production of new striatal neurons in young and adult rodents has been studied. However, it is unclear whether neonatal hypoxic/ischemic (H/I) brain injury-induced neuronogenesis in the striatum is transient or sustained, nor has it been established whether these new neurons arise from progenitors within the striatum or from precursors residing in the adjacent subventricular zone. Here, we report that from 2 weeks to 5 months after H/I there are more doublecortin-positive (Dcx+) cells and Dcx+/NeuN+ cells in the damaged striatum compared to the contralateral striatum. After the S-phase marker 5-bromo-2'-deoxyuridine (BrdU) was injected at both short and long intervals (2 days and 2 months) after H/I to label newly born cells, more BrdU+/Dcx+ and BrdU+/NeuN+ cells were observed in the ipsilateral striatum compared to the contralateral striatum. Retroviral fate-mapping studies demonstrated that these newly born striatal neurons are generated from precursors within the subventricular zone. Altogether, these observations indicate the neonatal brain initiates a prolonged regenerative response from the precursors of the subventricular zone (SVZ) that results in persistent production of new striatal neurons.
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PMID:Perinatal hypoxic/ischemic brain injury induces persistent production of striatal neurons from subventricular zone progenitors. 1776 1

Strategies to provide neuroprotection and to promote regenerative axonal outgrowth in the injured brain are thwarted by the plethora of axon growth inhibitors and the ligand promiscuity of some of their receptors. Especially, new neurons derived from ischemia-stimulated neurogenesis must integrate this multitude of inhibitory molecular cues, generated as a result of cortical damage, into a functional response. More often than not the response is one of growth cone collapse, axonal retraction and neuronal death. Therefore, characterization of the expression of inhibitory molecules in long-term surviving ischemic brains following stroke is important for designing selective therapeutics. Here, we describe a long-term recovery mouse model for cerebral ischemia in which a brief transient occlusion of the middle cerebral artery (30min) was followed by up to 30 days of long-term reperfusion. Significantly decreased grip strength motor function and increased expression of one of the major repulsive guidance cues, Semaphorin 3A (Sema3A) and its receptor Neuropilin1 (NRP1) occurred in brains of these mice. Interestingly, increased Doublecortin (DCX) expression occurred only in the lateral ventricular wall zone, but not in the dentate gyrus granule cell layer on the ischemic side of the brain. Importantly, no DCX positive cells were detected in the infarct core region after 30d ischemic recovery. Collectively, these studies demonstrated the sustained elevation of Sema3A/NRP1 expression in the ischemic territory, which may contribute to the inhibitory microenvironment responsible for preventing new neurons from entering the infarct area. This model will be of use as a platform for testing anti-inhibitory therapies to stroke.
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PMID:Sustained up-regulation of semaphorin 3A, Neuropilin1, and doublecortin expression in ischemic mouse brain during long-term recovery. 1816 77

Melatonin attenuates the short-term consequences of brain ischemia in several animal models. However, there is scant information regarding its efficacy for improving the long-term outcome. To further address that issue, we subjected gerbils to 5-min bilateral carotid occlusion. Some gerbils received acute peri-surgical administration of melatonin while others received continuous melatonin in their water. The gerbils' brains were histologically assessed at 20 wk postsurgery. Chronic but not acute melatonin attenuated ischemia-induced hyperactivity at 3 days postsurgery. Twenty weeks postsurgery, the ischemic gerbils showed varying degrees of bilateral loss of hippocampal CA1 pyramidal cells and elevation of glial fibrillary acidic protein immunoreactivity there. Both the cell loss and the immunoreactivity were markedly asymmetrical for some gerbils. Neither acute nor chronic melatonin altered this pattern of CA1 cell loss and glial immunoreactivity increase. Ischemia increased the number of CA1 cells that were immunoreactive for doublecortin (DCX), a marker for newborn neurons. This increase in CA1 DCX expression was not affected by either melatonin treatment. However, both acute and chronic melatonin reduced the number of DCX immunoreactive neurons in the dentate gyrus. Thus, neither acute nor chronic melatonin altered the long-term neural outcome of forebrain ischemia, although chronic administration seemed to attenuate the short-term behavioral effect. It is suggested that persistently high brain levels of melatonin may be essential for long-term neuroprotection against ischemia. The possibility that melatonin may modulate hippocampal neurogenesis merits further exploration both in normal animals and in models of brain insult.
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PMID:Chronic and acute melatonin effects in gerbil global forebrain ischemia: long-term neural and behavioral outcome. 1828 66

It is established that hippocampal neurogenesis is dynamically regulated by physiological and pathological stimuli including learning, environmental complexity, mental disorders and brain lesion. Little is known about factors regulating adaptive changes in neurogenesis. Using mu-opioid receptor (MOP)-knockout mice we addressed whether endogenous opioids influence ischemia-induced enhancement of hippocampal neurogenesis. Permanent middle cerebral artery occlusion (MCAO) produced similar corticostriatal infarcts in MOP-knockout and wildtype mice. Analyses of BrdU/doublecortin-colabelled cells in the granule cell layer 14 days after MCAO showed that ischemic knockouts contained more immature neurons generated during days 9-11 than wildtypes. After 29 days, similar quantities of BrdU/NeuN-labelled cells were found in ischemic knockout and wildtype mice, suggesting that granule cells that were formed in excess during days 9-11 in the knockouts were eliminated by day 29. Neurogenesis was similar in knockout and wildtype mice subjected to sham operation. In addition to a transient increase in neurogenesis, MCAO caused a transient up-regulation of preprodynorphin and preproenkephalin mRNA expression in the granule cell layer. Our findings suggest that activated signalling via endogenous opioids and the MOP limits the enhanced generation of neuronal cells after ischemic corticostriatal lesions.
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PMID:Endogenous opioids inhibit ischemia-induced generation of immature hippocampal neurons via the mu-opioid receptor. 1833 39

Recent studies have shown that neuroblasts migrate from the subventricular zone (SVZ) into the injured area after ischemic brain insults. However, it is not well understood which mechanism mediates this ectopic migration and which types of cells migrate into the damaged region from the SVZ. The present study was designed to investigate the characteristics of the migration of nestin-positive neural stem cells toward the region of ischemic injury after focal cortical ischemia. Nestin-eGFP transgenic mice were used to effectively model the migration of SVZ cells. Photothrombotic ischemia was induced by injection of rose bengal (30 mg/kg) and exposure to cold light. Migration of nestin-positive cells was examined using 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) and bromodeoxyuridine (BrdU) labeling. The number of nestin-positive cells was increased significantly in the peri-infarct area at 5 and 7 days after photothrombosis. A subset of nestin-positive cells was co-labeled with DiI or BrdU. Some of the nestin-positive cells co-expressed doublecortin (DCX) and only a few nestin-positive cells co-labeled with anti-epidermal growth factor receptor (EGFr) antibody. However, no nestin-positive cells were immunoreactive for glial fibrillary acidic protein (GFAP). The inhibition of matrix metalloproteinases (MMPs) using the MMP inhibitor, FN-439, decreased nestin-positive cells in the peri-infarct region at 7 days after photothrombosis. Although MMP-9 was not co-expressed in the nestin-positive cells in the peri-infarct cortex, MMP-9 did co-localize with GFAP-positive astrocytes. These results suggest that nestin-positive neural progenitor cells migrate into the peri-infarct cortex after photothrombotic ischemia and that MMP-9 is involved in the migration.
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PMID:Inhibition of matrix metalloproteinase-9 attenuated neural progenitor cell migration after photothrombotic ischemia. 1861 32

Peripheral stimulation and physical therapy can promote neurovascular plasticity and functional recovery after CNS disorders such as ischemic stroke. Using a rodent model of whisker-barrel cortex stroke, we have previously demonstrated that whisker activity promotes angiogenesis in the penumbra of the ischemic barrel cortex. This study explored the potential of increased peripheral activity to promote neurogenesis and neural progenitor migration toward the ischemic barrel cortex. Three days after focal barrel cortex ischemia in adult mice, whiskers were manually stimulated (15 min x 3 times/day) to enhance afferent signals to the ischemic barrel cortex. 5-Bromo-2'-deoxyuridine (BrdU, i.p.) was administered once daily to label newborn cells. At 14 days after stroke, whisker stimulation significantly increased vascular endothelial growth factor and stromal-derived factor-1 expression in the penumbra. The whisker stimulation animals showed increased doublecortin (DCX) positive and DCX/BrdU-positive cells in the ipsilateral corpus of the white matter but no increase in BrdU-positive cells in the subventricular zone, suggesting a selective effect on neuroblast migration. Neurogenesis indicated by neuronal nuclear protein and BrdU double staining was also enhanced by whisker stimulation in the penumbra at 30 days after stroke. Local cerebral blood flow was better recovered in mice that received whisker stimulation. It is suggested that the enriched microenvironment created by specific peripheral stimulation increases regenerative responses in the postischemic brain and may benefit long-term functional recovery from ischemic stroke.
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PMID:Enhanced neurogenesis and cell migration following focal ischemia and peripheral stimulation in mice. 1877 65

In the present study, cerebral ischemia was induced by a 10 min transient bilateral common carotid artery occlusion in rats combined with arterial blood pressure lowering to 37-42 mm Hg during occlusion. When histologically evaluated at 7 and 28 days after the forebrain ischemia (DAI) by staining with cresyl violet and Fluoro-Jade, the hippocampal CA1 region was most prominently damaged. At 7 DAI, treatment with cilostazol (60 mg/kg/day, orally) significantly reduced the neuronal damage in the CA1 region. The number of surviving neurons, visualized by NeuN immunostaining, in the CA1 region significantly increased at 7 and 28 DAI in the cilostazol-treated groups. To elucidate whether cilostazol enhances hippocampal neurogenesis after ischemia, we planned a co-labeling study using 5-bromo-2'-deoxyuridine (BrdU), NeuN (a marker for mature neurons) and doublecortin (DCX) (a marker for immature migratory neuroblasts). Double immunofluorescence staining at 7 DAI showed that cilostazol significantly increased the immunoreactivities of both DCX and phosphorylated cAMP-response element-binding protein (CREB) in the dentate gyrus that was co-expressed with BrdU. These results suggest that cilostazol has dual beneficial effects preserving the CA1 hippocampal region and promoting the generation of immature migratory neuroblasts in the dentate gyrus by upregulation of CREB phosphorylation after transient forebrain ischemia.
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PMID:Cilostazol preserves CA1 hippocampus and enhances generation of immature neuroblasts in dentate gyrus after transient forebrain ischemia in rats. 1893 64

Basic and clinical studies have revealed that depression is frequently observed following myocardial infarction (MI). We observed changes in neurons in the subgranular zone of the hippocampal dentate gyrus (DG) 14 days after chronic cardiac ischemia. Cresyl violet staining was conducted to examine neurodegeneration. Cresyl violet-positive neurons in the hippocampus in the MI-operated group were similar to those in the sham-operated group, and Fluoro-Jade B-positive cells were not observed in either group. Next, we observed changes in cell proliferation using Ki67 and in the differentiation of neuroblasts using doublecortin (DCX) in the DG. The number of Ki67- and DCX-positive cells in the subgranular zone of the DG in the MI-operated group was significantly increased compared to that in the sham-operated group. In addition, DCX-positive processes were prominent in the MI group. These results suggest that MI may influence cell proliferation and affect neuroblast differentiation in the subgranular zone of the DG.
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PMID:Enhanced cell proliferation and neuroblast differentiation in the rat hippocampal dentate gyrus following myocardial infarction. 1907 Nov 96

Neuroblasts in the subventricular zone (SVZ) proliferate markedly after brain ischemia, and migrate to the site of injury along with blood vessels. However, a large fraction of stroke-generated neuroblasts die shortly after being born, in part, because of local inflammation. In spontaneously hypertensive rats (SHRs) subjected to permanent middle cerebral artery occlusion, we primed E-selectin-specific regulatory T cells (Tregs) by repetitive intranasal administration of recombinant E-selectin to target local secretion of immunomodulating, antiinflammatory cytokines to activating blood vessel segments. E-selectin-tolerized SHRs had decreased infarction volumes, and increased numbers of Tregs in the cervical lymph nodes and ischemic brain. The brain Tregs were distributed primarily in periinfarct regions. E-selectin tolerization did not alter cellular proliferation in the ipsilateral SVZ after stroke, but the expression of tumor necrosis factor on vascular niche blood vessels was suppressed and both doublecortin protein levels and the number of newly generated neuroblasts or neurons were increased in the brain. This enhanced survival of neural progenitor cells and neurons was paralleled by improved functional performance. These studies suggest that E-selectin-specific Tregs can modulate the efficacy of neurogenesis after ischemia and promote repair after brain injury.
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PMID:Mucosal tolerance to E-selectin promotes the survival of newly generated neuroblasts via regulatory T-cell induction after stroke in spontaneously hypertensive rats. 1910 36


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