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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neuroprotective action of brain-derived neurotrophic factor (BDNF) was evaluated in a rat model of transient forebrain ischemia. A continuous intraventricular infusion of BDNF for 7 days starting immediately before the onset of ischemia significantly increased the number of pyramidal cells in the vulnerable CA1 sector of the hippocampus. In situ hybridization experiments suggest the neuroprotection to be mediated via trkB-receptors in the hippocampus. The data indicate a therapeutic potential for the treatment of cerebral ischemia.
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PMID:Brain-derived neurotrophic factor protects against ischemic cell damage in rat hippocampus. 801 17

The rat brain-derived neurotrophic factor (BDNF) gene consists of four short 5'-exons linked to separate promoters and one 3'-exon encoding the mature BDNF protein. Using in situ hybridization we demonstrate here that kindling-induced seizures, cerebral ischaemia and insulin-induced hypoglycaemic coma increase BDNF mRNA levels through insult- and region-specific usage of three promoters within the BDNF gene. Both brief (2 min) and longer (10 min) periods of forebrain ischaemia induced significant and major increases only of exon III mRNA in the dentate gyrus. Following hypoglycaemic coma (1 and 30 min), exon III mRNA was markedly elevated in the dentate gyrus and, in addition, exon I mRNA showed a moderate increase. Single and recurrent (n = 40) hippocampal seizures significantly increased expression of exon I, II and III mRNAs in the dentate gyrus granule cells. After recurrent seizures, including generalized convulsions, there were also major increases of both exon I and III mRNAs in the CA3 region, amygdala, piriform cortex and neocortex, whereas in the hippocampal CA1 sector marked elevations were detected only for exon III mRNA. The insults had no effect on the level of exon IV mRNA in the brain. The region- and insult-specific pattern of promoter activation might be of importance for the effectiveness of protective responses as well as for the regulation of plastic changes following brain insults.
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PMID:Brain insults in rats induce increased expression of the BDNF gene through differential use of multiple promoters. 802 13

Recent studies show that focal brain injury, cerebral ischaemia, hypoglycaemia and seizures increase the expression of c-fos and brain-derived neurotrophic factor in brain. Here we report that hippocampal focal brain injury transiently induces the immediate early genes c-fos, jun-B, c-jun and krox-24 (zif-268) messenger RNA and protein and brain-derived neurotrophic factor messenger RNA in rat dentate gyrus neurons, an effect that was blocked by the N-methyl-D-aspartate receptor antagonist MK-801. Prior administration of the protein synthesis inhibitor cycloheximide super-induced immediate early gene messenger RNA, abolished immediate early gene protein induction, but had no effect on injury-mediated induction of brain-derived neurotrophic factor messenger RNA. Thus, while N-methyl-D-aspartate receptor activation results in the induction of both immediate early genes and brain-derived neurotrophic factor messenger RNA, de novo synthesis of immediate early gene proteins is not critical for the increased expression of brain-derived neurotrophic factor messenger RNA seen in brain after focal injury. These results suggest that brain-derived neurotrophic factor is induced after injury as an immediate early gene.
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PMID:Brain-derived neurotrophic factor is induced as an immediate early gene following N-methyl-D-aspartate receptor activation. 811 41

The protein-tyrosine kinases Trk, TrkB, and TrkC are signal-transducing receptors for a family of neurotrophic factors known as the neurotrophins. Here we show that seizures induced by hippocampal kindling lead to a rapid, transient increase of trkB mRNA and protein in the hippocampus. TrkB is a component of a high affinity receptor for brain-derived neurotrophic factor (BDNF). No change was detected in mRNAs for Trk or TrkC, components of the high affinity nerve growth factor or neurotrophin-3 receptors, respectively. trkB mRNA was also transiently increased in the dentate gyrus following cerebral ischemia and hypoglycemic coma; these treatments had no effect on trk and trkC mRNAs. The increase in trkB mRNA and protein showed the same time course and distribution as the increase in BDNF mRNA. These data suggest that BDNF and its receptor may play a local role within the hippocampus in kindling-associated neural plasticity and in neuronal protection following epileptic, ischemic, and hypoglycemic insults.
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PMID:Increased production of the TrkB protein tyrosine kinase receptor after brain insults. 843 8

The neuroprotective effect of neurotrophic factors has been demonstrated in experimental cerebral ischaemia recently. These include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and basic fibroblast growth factor (basic FGF). The neuroprotective effect of ciliary neurotrophic factor (CNTF), however, has not been studied so far. We have examined the neuroprotective effect of recombinant rat CNTF in a rat forebrain ischaemia model. A continuous infusion of CNTF was started 1 week before the induction of ischaemia and continued until 1 week after the ischaemia. Reversible forebrain ischaemia was induced by 7 minutes of bilateral carotid occlusion with hypotension. Neuronal cell death in the hippocampal CA1 sector was evaluated 1 week after the ischaemia. For the control group artificial CSF (cerebrospinal fluid) was infused instead of CNTF. Per cent neuronal cell death was 83.4 +/- 5.9% (mean +/- SEM, n = 5) in the control group, and 71.1 +/- 10.0% (mean +/- SEM, n = 5) in the CNTF group. Although percentage of neuronal cell death was lower in the CNTF group, the difference was not statistically significant. This result suggests that the protective effect of CNTF in the rat forebrain ischaemia model may be limited compared with other neurotrophic factors. It is considered that the number of neurons protected by CNTF may be small.
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PMID:Effect of CNTF on ischaemic cell damage in rat hippocampus. 880 Mar 34

Cerebral ischemia is known to induce the expression of several immediate early genes (IEGs), including c-fos and c-jun, which subsequently regulate a number of late effector genes. In this study, we examined the expression of NGFI-B (or nur 77) mRNA in a rat focal cerebral ischemia-reperfusion model. NGFI-B is a member of the IEGs which encodes for a nuclear receptor and is rapidly induced by nerve growth factor (NGF). Northern blot analysis showed a rapid but transient enhancement of NGFI-B mRNA, a peak level for which was observed at 30 min of reperfusion following 60 min ischemic insult. At the peak level, quantitative analysis of the blot indicated a 12-fold and 4-fold increase of NGFI-B mRNA in the ischemic cortex and ipsilateral hippocampus, respectively, as compared to the sham-operated control. No apparent changes in mRNA levels were observed within contralateral sites of the cortex. Results from in situ hybridization showed that severe ischemia (60 min) resulted in a marked increase of NGFI-B mRNA throughout the entire ischemic cerebral cortex. The increase was particularly notable in the frontal, occipital, perirhinal and piriform cortical regions and in the dentate gyrus and CAI-3 regions of the ipsilateral hippocampus. A marked induction was also noted in the ipsilateral caudate putamen. Unlike the induction profile of NGFI-B mRNA, severe ischemia resulted in bilateral increases of its family gene, NGFI-A mRNA. The spatial induction profile is similar to that of NGFI-B mRNA in both hemispheres, except within the region of the contralateral dentate gyrus which showed low levels of NGFI-A mRNA. The expression pattern of NGF and BDNF mRNA, upstream genes of NGFI-B, were also examined. Interestingly the temporal and spatial expression patterns of BDNF mRNA were very similar to that of NGFI-A mRNA under the same conditions, whereas increased NGF and NGFI-B mRNA were observed only in the ipsilateral hemisphere. It is likely that multiple and/or overlapping pathways are activated subsequent to ischemic challenge which in turn are crucial for cel survival and/or functional recovery following focal cerebral ischemia.
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PMID:Expression of NGFI-B mRNA in a rat focal cerebral ischemia-reperfusion model. 903 28

We recently reported that cortical spreading depression (CSD), used to precondition rat brain, reduced cortical infarction volume resulting from focal cerebral ischemia by middle cerebral artery occlusion (MCAO) 3 days later. The mechanisms underlying this protective effect by CSD remains to be explored. In this study, we confirm that CSD is neuroprotective when KCl is applied epidurally rather than intracortically. Neocortical infarct volume was 101.3+/-48.5 mm3 and 45.3+/-44.1 mm3 in the sham and CSD group, respectively (p<0.05). Using image analysis, we identified the cortical region spared from infarction by the prior CSD. We then determined the distribution of brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) mRNA and the time course of their expression in groups of animals treated with CSD and their controls. We also examined the response of astrocytes to CSD using glial fibrillary acidic protein (GFAP) as a marker. In situ hybridization (done at 0, 3, 12, 24, 72 or 168 h after CSD) showed significant elevation of BDNF mRNA in the cortex immediately after CSD in a distribution surrounding the spared cortex, while bFGF mRNA rose 12 h after CSD and appeared more within the core of the ischemic region. Immunohistochemistry (done at 1, 3 or 7 days after CSD) demonstrated GFAP in the neocortex, with a peak at 3 days after CSD. Heat shock protein 72 (HSP72) expression was not affected by CSD. We concluded that upregulation of trophic factors and activation of glial cells may contribute to the neuroprotection induced by CSD.
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PMID:Cortical spreading depression activates trophic factor expression in neurons and astrocytes and protects against subsequent focal brain ischemia. 975 93

Expression of brain-derived neurotrophic factor (BDNF) may play a role in the mechanism of neuronal cell death after cerebral ischemia. We investigated the changes in levels of mRNAs encoding BDNF and its promoters in the rat brain after transient forebrain ischemia. Transient forebrain ischemia was induced by occlusion of bilateral common carotid arteries and systemic hypotension for 8 min. The alterations in BDNF gene expression in the hippocampus and in the cerebral cortex were examined by in situ hybridization using a mouse BDNF cDNA probe and cDNA probes including exon-specific promoters. BDNF transcripts were rapidly enhanced after the ischemic insult, both in the hippocampus and the cerebral cortex. NBQX suppressed the enhanced gene expression of BDNF markedly in the dentate gyrus (DG). In contrast, MK-801 had little effect on BDNF expression. In the piriform cortex, MK-801 or NBQX reduced the expression only moderately. After the ischemic insult, promoter specific BDNF 5'-exon I and exon III were increased remarkably in the DG. The increase in exon I in DG was suppressed partially by MK-801 and NBQX, while the increase in exon III in CA3 was suppressed by MK-801 but that in DG was not suppressed by either antagonist. In the piriform cortex, exon III was increased remarkably and this increase was not influenced by either agonist. These results suggest that the gene expression of BDNF was enhanced by transient ischemia both in the hippocampus and the cerebral cortex and that the cerebral ischemia stimulated at least two different promoter- and neuron type-specific pathways regulating expression of the BDNF gene mediated by glutamate receptors of non-NMDA type and NMDA type.
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PMID:Increases in levels of brain-derived neurotrophic factor mRNA and its promoters after transient forebrain ischemia in the rat brain. 976 65

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

Several lines of evidence indicate that a rapid loss of neuronal protein kinase C (PKC) activity is a characteristic feature of cerebral ischemia and is a necessary step in the NMDA-induced death of cultured neurons. Exposing embryonic day 18 primary rat cortical neurons to 50 microM NMDA or 50 microM glutamate for 10 min caused approximately 80% cell death over the next 24 h, but excitotoxic death was largely averted, i.e., by 70-80%, in cells pretreated with brain-derived neurotrophic factor (BDNF). An 8-h preexposure to BDNF (50-100 ng/ml) maximally protected cortical cells from the effects of NMDA and glutamate, although the transient application of BDNF between 8 and 4 h before NMDA was equally protective. These effects of BDNF were abolished at supralethal, i.e., >100 microM, NMDA concentrations. It is significant that BDNF pretreatment prevented the inactivation of PKC in cortical cells normally seen 30 min to 2 h following lethal NMDA or glutamate exposure. This BDNF effect did not arise from changes in NMDA channel activity because neither whole-cell NMDA current amplitudes nor increases in intracellular free Ca2+ concentration were altered by the 8-h BDNF pretreatment. Furthermore, BDNF offered no neuroprotection to cells treated with the PKC inhibitors staurosporine (10-20 nM), calphostin C (1-2.5 microM), or GF-109203X (100 nM) at the time of NMDA addition. These results underscore the importance of PKC inactivation in glutamate-induced neuronal death. They also suggest that BDNF neuroprotection arises, at least in part, via its ability to block the mechanism by which pathophysiological Ca2+ influx through the NMDA receptor causes membrane PKC inactivation.
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PMID:Evidence that brain-derived neurotrophic factor neuroprotection is linked to its ability to reverse the NMDA-induced inactivation of protein kinase C in cortical neurons. 988 60


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