Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of the mRNAs of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and the neurotrophin receptor, TrkB, was studied in the rat hippocampus by in situ hybridization following normothermic (37 degreesC) and protective hypothermic (33 degreesC) transient cerebral ischemia of 15 min duration. In the resistant dentate gyrus, normothermic ischemia transiently induced NGF mRNA at around 8 h of recovery, while the NT3 mRNA levels were depressed over at least a 24-h recovery period. The levels of BDNF and TrkB were transiently and markedly elevated with a maximal expression at 24 h of recovery. Intraischemic hypothermia reduced the induction of NGF mRNA, while the increase of BDNF mRNA expression occurred earlier during recovery, and the post-ischemic NT3 mRNA depression was not affected. Also, the expression of TrkB mRNA was enhanced, and occurred concomitantly with the elevation of BDNF mRNA. In contrast, there were no changes in neurotrophin and TrkB mRNA in the CA3 and CA1 regions. The expression of BDNF mRNA at 24 h after normothermic ischemia, was attenuated by intraischemic hypothermia. We conclude that, the expressions of NGF, BDNF, NT3 or TrkB mRNA in ischemia-sensitive hippocampal subregions are not increased by protective hypothermia. In contrast, hypothermia induces neurotrophin mRNA alterations in the ischemia-resistant dentate gyrus that may convey protection to sensitive regions.
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PMID:The effect of hypothermia on the expression of neurotrophin mRNA in the hippocampus following transient cerebral ischemia in the rat. 983 92

The survival of different neuron types and the expression of the p75 neurotrophin receptor (p75(NTR)) after focal cerebral ischemia were studied in the mouse striatum using immunocytochemical and histochemical techniques and stereological procedures. As assessed at 1 week after 30 min of middle cerebral artery occlusion, the order of vulnerability was projection neurons > parvalbumin-expressing interneurons > nitric oxide synthase-containing interneurons > cholinergic interneurons. Within the ischemic lesion, projection neurons were almost completely lost whereas cholinergic interneurons were spared. Calretinin-immunoreactive interneurons also seemed resistant to the insult. Expression of p75(NTR) was induced in cholinergic interneurons within the lesioned area, raising the possibility of a protective action. However, the number of cholinergic interneurons was unaffected in p75(NTR) knockout mice subjected to the same ischemic insult. These quantitative data demonstrate that striatal neurons in the mouse are differentially susceptible to ischemic damage and argue against a significant role of p75(NTR) for the high resistance of cholinergic interneurons.
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PMID:Upregulation of p75 neurotrophin receptor after stroke in mice does not contribute to differential vulnerability of striatal neurons. 1135 48

To explore the role of neurotrophin-3 (NT-3) during cerebral ischemia, NT-3-deficient brains were subjected to transient focal ischemia. Conditional mutant brains produced undetectable amounts of NT-3 mRNA, whereas the expression of the neurotrophin, BDNF, the NT-3 receptor, TrkC, and the nonselective, low-affinity neurotrophin receptor p75NTR, were comparable to wild-type. Baseline absolute blood flow, vascular and neuroanatomical features, as well as physiological measurements were also indistinguishable from wild-type. Interestingly, the absence of NT-3 led to a significantly decreased infarct volume 23 h after middle cerebral artery occlusion. Consistent with this, the addition of NT-3 to primary cortical cell cultures exacerbated neuronal death caused by oxygen-glucose deprivation. Coincubation with the oxygen free radical chelator, trolox, diminished potentiation of neuronal death. NT-3 also enhanced neuronal cell death and the production of reactive oxygen species caused by oxidative damage inducing agents. We conclude that endogenous NT-3 enhanced neuronal injury during acute stroke, possible by increasing oxygen-radical mediated cell death.
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PMID:Neurotrophin-3 promotes cell death induced in cerebral ischemia, oxygen-glucose deprivation, and oxidative stress: possible involvement of oxygen free radicals. 1184 82

Induction of mild hypothermia improves neurologic outcome after global cerebral ischemia. This study measured levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in hippocampal tissue of rats after resuscitation from 8 minutes of normothermic, asphyxial cardiac arrest. After resuscitation, rats were maintained either at normal temperature (37 degrees C) or cooled to mild hypothermia (33 degrees C, beginning 60 minutes after resuscitation). After 12 or 24 hours, neurotrophin levels in hippocampus were measured by immunoblotting. Ischemia and reperfusion increased hippocampal levels of BDNF. Induction of hypothermia during reperfusion potentiated the increase in BDNF after 24 hours, but not after 12 hours. Levels of NGF were not increased by postresuscitation hypothermia. Hypothermia also increased tissue levels and tyrosine phosphorylation of TrkB, the receptor for BDNF. Increased BDNF levels were correlated with activation of the extracellularly regulated kinase (ERK), a downstream element in the signal transduction cascade induced by BDNF. In contrast to the many deleterious processes during ischemia and reperfusion that are inhibited by induced hypothermia, increasing BDNF levels is a potentially restorative process that is augmented. Increased activation of BDNF signaling is a possible mechanism by which mild hypothermia is able to reduce the neuronal damage typically occurring after cardiac arrest.
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PMID:Hypothermic reperfusion after cardiac arrest augments brain-derived neurotrophic factor activation. 1214 69

In this report, we provide direct demonstration that the neurotrophin nerve growth factor (NGF) is released in the extracellular space in an activity-dependent manner in its precursor form (proNGF) and that it is in this compartment that its maturation and degradation takes place because of the coordinated release and the action of proenzymes and enzyme regulators. This converting protease cascade and its endogenous regulators (including tissue plasminogen activator, plasminogen, neuroserpin, precursor matrix metalloproteinase 9, and tissue inhibitor metalloproteinase 1) are colocalized in neurons of the cerebral cortex and released upon neuronal stimulation. We also provide evidence that this mechanism operates in in vivo conditions, as the CNS application of inhibitors of converting and degrading enzymes lead to dramatic alterations in the tissue levels of either precursor NGF or mature NGF. Pathological alterations of this cascade in the CNS might cause or contribute to a lack of proper neuronal trophic support in conditions such as cerebral ischemia, seizure and Alzheimer's disease or, conversely, to excessive local production of neurotrophins as reported in inflammatory arthritis pain.
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PMID:Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor, and its degradation by a protease cascade. 1661 25

In animal models of neurological disorders for cerebral ischemia, Parkinson's disease, and spinal cord lesions, transplantation of mesenchymal stem cells (MSCs) has been reported to improve functional outcome. Three mechanisms have been suggested for the effects of the MSCs: transdifferentiation of the grafted cells with replacement of degenerating neural cells, cell fusion, and neuroprotection of the dying cells. Here we demonstrate that a restricted number of cells with differentiated astroglial features can be obtained from human adult MSCs (hMSCs) both in vitro using different induction protocols and in vivo after transplantation into the developing mouse brain. We then examined the in vitro differentiation capacity of the hMSCs in coculture with slices of neonatal brain cortex. In this condition the hMSCs did not show any neuronal transdifferentiation but expressed neurotrophin low-affinity (NGFR(p75)) and high-affinity (trkC) receptors and released nerve growth factor (NGF) and neurotrophin-3 (NT-3). The same neurotrophin's expression was demonstrated 45 days after the intracerebral transplantation of hMSCs into nude mice with surviving astroglial cells. These data further confirm the limited capability of adult hMSC to differentiate into neurons whereas they differentiated in astroglial cells. Moreover, the secretion of neurotrophic factors combined with activation of the specific receptors of transplanted hMSCs demonstrated an alternative mechanism for neuroprotection of degenerating neurons. hMSCs are further defined in their transplantation potential for treating neurological disorders.
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PMID:Induction of neurotrophin expression via human adult mesenchymal stem cells: implication for cell therapy in neurodegenerative diseases. 1743 54

Recently, it was demonstrated that TRPM7 is an essential mediator of anoxia-induced neuronal death. Meanwhile, nerve growth factor (NGF) is known to have survival and neuroprotective effects by interacting with the high affinity neurotrophin receptor, tropomyosin-related kinase A (trkA). In the present study, we found that electroacupuncture (EA) treatment could up-regulate trkA expression after focal cerebral ischemia in rats. At the same time, EA therapy obviously decreased the high expression of TRPM7 induced by ischemia. Using K252a to inhibit trkA, we found that the EA-mediated down-regulation of TRPM7 was significantly suppressed in rats subjected to cerebral ischemia. TrkA can utilize two distinct signaling pathways: the phosphatidylinositol 3-kinase (PI3K) pathway and the extracellular signal-related kinase (ERK) pathway. We found that the effect of EA on TRPM7 was also inhibited by a PI3K inhibitor, while an ERK inhibitor had no effect. Taken together, our findings suggest that EA can reverse the ischemia-induced increase of TRPM7 levels through the trkA-PI3K pathway.
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PMID:Electroacupuncture regulates TRPM7 expression through the trkA/PI3K pathway after cerebral ischemia-reperfusion in rats. 1790 84

It is known that the activation of 5-hydroxytryptamine receptor type 1A (5HT(1A) receptor) may protect against brain damage induced by transient global ischemia. The biochemical mechanisms that underlie this neuroprotective effect remain however to be fully elucidated. Given that serotonergic drugs may regulate N-methyl-d-aspartate (NMDA) receptor function, which is implicated in events leading to ischemia-induced neuronal cell death, and also stimulate the expression of brain-derived neurotrophic factor (BDNF), which is down-regulated in cerebral ischemia, we sought to determine the effects of the selective 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), on the levels of NMDA receptor NR1 subunit and BDNF in gerbil hippocampus after transient global cerebral ischemia. Pretreatment with 8-OH-DPAT (1 mg/kg) prevented the neuronal loss in CA1 subfield 72 h after ischemia and also the dramatic decrease in BDNF immunoreactivity observed in this area at an earlier time. NMDA receptor NR1 levels in whole hippocampus were not affected 24 h after ischemia, but the levels of the subunit phosphorylated at the protein kinase A (PKA) site, pNR1(Ser897), were significantly increased, and this increase was prevented by the same 8-OH-DPAT dose, a probable consequence of the increased phosphatase 1 (PP1) enzyme activity found in ischemic gerbils pretreated with the 5-HT(1A) receptor agonist. The results indicate that both NR1 subunit phosphorylation and the neurotrophin BDNF account, at least in part, for the neuroprotective effect of 8-OH-DPAT on cell damage induced by global ischemia in the gerbil hippocampus and support the potential interest of 5-HT1A receptor activation in the search for neuroprotective strategies.
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PMID:Neuroprotective effects of serotonin 5-HT 1A receptor activation against ischemic cell damage in gerbil hippocampus: Involvement of NMDA receptor NR1 subunit and BDNF. 1826 31

Panax Notoginseng Burk (PN) has been reported to improve blood circulation, as well as learning and memory functions. The purpose of the present study was to investigate the effect of PN on learning and memory functions in chronic cerebral infarct rats. A cerebral infarct animal model was established by blocking the blood flow of both common carotid arteries and right middle cerebral artery for 90 min followed by reperfusion for 4 weeks. PN (0.5 g/kg) was administered orally 3 days per week for 4 weeks, whereas the control group provided bait and water only. The learning and memory functions were estimated by measuring how successful rats were able to negotiate an 8-arm radial maze test; the test was performed after operation once a week for 4 weeks. Finally, the rats were sacrificed and their brains were removed. The brains were sectioned and analyzed for ED1, glial fibrillary acid protein (GFAP), nuclear factor-kappaB, and brain derivative neurotrophin factor (BDNF) and beta-secretase by immunostaining. Cerebral infarct rats given PN were able to successfully navigate the 8-arm radial maze test four weeks after cerebral infarction. PN also increased ED1, BDNF and beta-secretase immunoreactive cells, but did not increase GFAP and NF-kappaB immunoreactive cells. PN attenuated the reduction in learning and memory functions induced by cerebral infarction in cerebral ischemia-reperfusion injured rats; it also increased the amount of activated microglia and BDNF. These data suggest that the effect of PN, at least in part, is closely related to the increase in BDNF that was generated by activated microglia. The effect that PN has on astrocytes, NF-kappaB and beta-secreatase immunoreactive cells requires further study.
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PMID:Panax Notoginseng Burk attenuates impairment of learning and memory functions and increases ED1, BDNF and beta-secretase immunoreactive cells in chronic stage ischemia-reperfusion injured rats. 1871 66

Transient global cerebral ischemia elicits a nearly total neuronal cell death in the hippocampal CA1 sector, accompanied by a marked microglial and astroglial proliferation. The molecular mechanisms regulating the postischemic glial reaction in the primate brain remain obscure. Here we present in situ evidence that proliferating postischemic microglia in adult monkey CA1 sector express the neurotrophin receptor TrkA, while activated astrocytes were labeled for the TrkA ligand nerve growth factor (NGF) and the tyrosine kinase TrkB, a receptor for brain-derived neurotrophic factor (BDNF). These results implicate NGF and BDNF as regulators of postischemic glial proliferation in adult primate hippocampus.
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PMID:Expression of neurotrophin receptors by proliferating glia in postischemic hippocampal CA1 sector of adult monkeys. 1878 30


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