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 induction of the heme oxygenase-1 (HO-1) protein, also called HSP32, was compared to HSP70 heat shock protein induction following focal ischemia. Adult Sprague-Dawley male rats (n = 14) were subjected to either 30 min or 2 h of focal cerebral ischemia using the suture, middle-cerebral-artery (MCA) occlusion model. Controls (n = 4) had sham surgery. Following 24 h of reperfusion, subjects were killed and their brains stained immunocytochemically for HO-1 and the HSP70 heat shock proteins. One day following 30 min of ischemia, HO-1 and HSP70 staining in striatum occurred mainly in endothelial cells in infarcts and in glial cells surrounding the areas of infarction. Following the 30 min ischemia HO-1 was not induced in cortex whereas HSP70 was induced in cortical neurons in the MCA distribution. One day following 2 h of MCA ischemia, both HO-1 and HSP70 were induced in neurons in cortex in the MCA distribution. HO-1, however, was induced in glial cells throughout ipsilateral cortex, inside as well as outside the MCA distribution. This suggests that translation and/or transcription of the HO-1 and HSP70 genes are blocked in neurons and glia destined to die within infarcts, whereas translation of these stress genes continues in the endothelial cells. The duration of ischemia required to induce HSP70 in cortical neurons appears to be less than that required to induce HO-1 in cortical glia. Prolonged spreading depression and/or diffuse hemispheric ischemia may induce HO-1 in glia throughout the ipsilateral cortex via immediate early gene activation of the AP-1 site in the HO-1 promoter. Since HO-1 degrades heme, a pro-oxidant, to antioxidant molecules, the induction of HO-1 may augment oxidative defense mechanisms compromised by cerebral ischemia.
Brain Res Mol Brain Res 1996 Apr
PMID:Heme oxygenase-1 (HO-1) protein induction in rat brain following focal ischemia. 873 52

Recently, many studies have demonstrated the induction of stress proteins in the mammalian nervous system under various pathological conditions. These altered genetic programs may function to protect individual cells against stressful conditions. However, little is known about the molecular mechanisms regulating these stress responses in animals. We report here the activation of a heat shock factor (HSF) in the rat brain during cerebral ischemia or after heat shock. Gel mobility shift assays revealed an increase in DNA binding activity to the heat shock element (HSE) during the early phases of ischemia. Supershift experiments using specific antisera against HSF1 and HSF2 showed that the ischemia-induced HSE-binding activity was mainly due to HSF1. In the heat-shocked brain, HSF1 was also activated, and the HSE-binding activity was higher in the cerebellum than in the cerebral cortex or hippocampus; Western blot analysis also showed that HSF1 was more abundant in the cerebellum than in the other two brain regions. Our results indicate that heat shock gene transcription is regulated by the activation of HSF1 in both cerebral ischemia and heat shock, and that different brain regions display differential sensitivities in their stress response. The cellular signals for heat shock gene transcription under in vivo pathological conditions will also be discussed.
Brain Res Mol Brain Res 1995 Dec 28
PMID:Activation of heat shock factor 1 in rat brain during cerebral ischemia or after heat shock. 875 Aug 29

The expression of mRNA for the Fas antigen, a membrane-associated protein mediating apoptosis, was localized by in situ hybridization histochemistry in murine brains following 30 min of global cerebral ischemia. Six hours following the ischemia, many labeled cells were detected anew throughout the brain. The hybridization was seen in the small neural cells and in the cells along the walls of the ventricles and vessels, and became undetectable 24 h following the ischemia. These results suggest that the Fas antigen is expressed in the neuron, glia and periventricular cells of the post-ischemic brain.
Brain Res Mol Brain Res 1995 Dec 01
PMID:Localization of Fas antigen mRNA induced in postischemic murine forebrain by in situ hybridization. 875 Aug 74

The recently cloned G protein-coupled adenosine A3 receptor has been proposed to play a role in the pathophysiology of cerebral ischemia. Because phospholipase C activation occurs as a very early response to brain ischemia, we evaluated the ability of A3- selective and nonselective adenosine analogues to elicit phosphoinositide hydrolysis. In myo-[3H]inositol-labeled rat striatal and hippocampal slices, A3 agonists stimulated formation of [3H]inositol phosphates in a concentration-dependent manner. In striatum, the potency order was 2-chloro-N6-(3-iodobenzyl)- adenosine-5'-N-methyluronamide > or = N6-(3-iodobenzyl)- adenosine-5'-N-methyluronamide >> N-methyl-1,3-di-n-butylxanthine-7-beta-D-ribofuronamide > or = 5'-N-ethylcarboxamidoadenosine > or = N6-2-(4-aminophenyl)-ethyladenosine > N6-(p-sulfophenyl)-adenosine = 1,3-dibutylxanthine-7- riboside, which is identical to the potency order in binding studies at cloned rat A3 receptors. Stimulation of phospholipase C activity was abolished by guanosine-5'-O-(2-thiodiphosphate), confirming the involvement of a G protein-coupled receptor. Activation of phospholipase C was higher in the striatum than in the hippocampus, consistent with A3 receptor densities. Stimulation of phospholipase C activity by adenosine analogues was only modestly antagonized by xanthine derivatives and at much higher concentrations than needed for blocking adenosine A1, A2A, and A2b receptors. In the presence of an A1/A2 antagonist, a selective A3 in rat striation. Thus, stimulation of phospholipase C activity agonist only weakly inhibited forskolin-stimulated adenylyl cyclase activity represents a principal transduction mechanism for A3 receptors in mammalian brain, and perhaps A3 receptor-mediated increases of inositol phosphates in the ischemic brain contribute to neurodegeneration by raising intracellular calcium levels.
Mol Pharmacol 1995 Dec
PMID:G protein-dependent activation of phospholipase C by adenosine A3 receptors in rat brain. 884 3

We employed a canine model to test the effects of global cerebral ischemia and reperfusion on binding to alpha-amino-3-hydroxy-5-methyl- 4-isoxazole proprionate (AMPA), kainate (KA), and metabotropic glutamate receptors. Ischemia was induced by 10 min of cardiac arrest, followed by restoration of spontaneous circulation for periods of 0, 0.5, 2, 4, and 24 h. Frozen sections were prepared from parietal and temporal cortex, hippocampus, and striatum, and in vitro autoradiography was performed with one of three radioligands: [3H]AMPA, [3H]KA, or [3H] glutamate (using conditions allowing specific labeling of the metabotropic binding site). In striatum, metabotropic binding was unchanged, whereas AMPA and KA binding decreased by 20-30% at 30 min postischemia, remaining depressed through 24 h. In cortex, AMPA and metabotropic binding were decreased at several time-points after ischemia and recirculation, particularly in parietal cortex, whereas KA binding was unaffected in this tissue. Binding to hippocampal regions was largely unchanged, except for a decrease in KA binding at 2 and 4 h postischemia. These findings contrast with results from parallel studies showing increased striatal binding to NMDA receptors following ischemia. Decreased binding to non-NMDA glutamate receptors in striatum and parietal cortex may serve to protect against damage mediated through these receptors.
Mol Chem Neuropathol 1996 Sep
PMID:Non-NMDA glutamate receptor binding in canine brain after global cerebral ischemia and reperfusion. 888 39

The induction of focal cerebral ischaemia in rats by middle cerebral artery occlusion has previously been shown to increase, over time, the mRNA levels of the heat shock proteins (HSPs) 27 and 70. However, the levels of HSP90 mRNA remain constant. In contrast, during global ischaemia, HSP70 and HSP90 mRNA levels are both raised, particularly in the CA1 neurons in the hippocampus, an area that is resistant to the insult in comparison to the surrounding regions. HSP27 mRNA is raised in the neuroglia in the subregions of the hippocampus. However, the protein levels of HSP27, 70 and 90 have not been characterised in focal ischaemia. With this data in mind, we have carried out a comparative study of HSP27, 56, 60, 70 and 90 mRNA and protein levels during focal cerebral ischaemia in rats, up to 24 h post-occlusion. We have shown that HSP70 and HSP27 mRNA levels are increased and also that HSP60 mRNA levels (which had also not previously been characterised in this model of focal ischaemia) are significantly raised. HSP90 and HSP56 mRNAs were not significantly elevated. On Western blot analysis, the inducible HSP72 protein was first detected at 8 h post-occlusion, HSP27 protein was detected only at 24 h post-occlusion and HSP60 protein, although constitutive, appeared to increase at 24 h post-occlusion. HSP56 protein levels appeared to rise on the occluded side, but HSP90 protein levels remained constant.
Brain Res Mol Brain Res 1996 Dec
PMID:Focal cerebral ischaemia increases the levels of several classes of heat shock proteins and their corresponding mRNAs. 901 79

We have studied the beneficial effects of S-adenosyl-L-methionine (SAM) tosylate on blood-brain barrier (BBB) breakdown and neuronal survival after transient cerebral ischemia in gerbils. BBB breakdown experiments were performed in pentobarbital anesthetized gerbils subjected to 10 min of bilateral carotid artery occlusion and 6 h of reperfusion. For BBB breakdown measurements, SAM (120 mg/kg, i.p.) was administered to gerbils just after occlusion and thereafter every hour up to 5 h. Fluorometric measurements quantified the blood-brain permeability tracer, Evans blue (EB). SAM treatment significantly reduced the BBB breakdown as indicated by reduced levels of EB fluorescence. Neuronal count experiments were conducted in gerbils subjected to transient ischemia and 7 days of reperfusion. For neuronal count experiments SAM (15-120 mg/kg) was administered at 6 and 12 h after reperfusion, and twice each day thereafter for 7 days. SAM dose dependently protected the hippocampal CA1 neurons assessed by histopathological methods. SAM has a beneficial effect on the outcome of ischemic injury by reducing the BBB breakdown and neuronal death.
Brain Res Mol Brain Res 1997 Feb
PMID:Beneficial effects of S-adenosyl-L-methionine on blood-brain barrier breakdown and neuronal survival after transient cerebral ischemia in gerbils. 903 Jul 7

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.
Brain Res Mol Brain Res 1996 Dec 31
PMID:Expression of NGFI-B mRNA in a rat focal cerebral ischemia-reperfusion model. 903 28

Experiments were conducted to evaluate the effects of desmethyl tirilazad (10 mg/kg, i.p.), a 21-aminosteroid, on constitutive nitric oxide synthase (cNOS) activity and cyclic guanosine monophosphate (cGMP) levels in brain homogenates of rats subjected to cerebral global transient ischemia induced by bilateral clamping of the carotids for 30 minutes and reduction of arterial pressure (to 50-60 mmHg) by intravenous infusion of 1.5 ml of a solution of trimethaphan (5 mg/ml). Our results show that ischemia induces a rise in cNOS activity (from 62.0 +/- 6.1 to 133.3 +/- 13.3 pmol/min/mg protein) and cGMP levels (from 459.3 +/- 49.6 to 1074.1 +/- 132.1 fmol/mg protein). Pretreatment with desmethyl tirilazad abolishes these increases. These results are in agreement with the neuroprotective efficacy of desmethyl tirilazad in cerebral ischemia.
Res Commun Mol Pathol Pharmacol 1997 Jan
PMID:Desmethyl tirilazad reduces brain nitric oxide synthase activity and cyclic guanosine monophosphate during cerebral global transient ischemia in rats. 905 47

We employed a canine model to test whether binding to the N-methyl-D-aspartate (NMDA) class of glutamate receptor channels is altered by global cerebral ischemia and/or reperfusion. Ischemia was induced by 10-min cardiac arrest, followed by restoration of spontaneous circulation for periods of 0, 0.5, 2, 4, and 24 h. In vitro autoradiography was performed on frozen brain sections with three radioligands: [3H]glutamate (under conditions to label the NMDA site), [3H]glycine, and [3H]MK-801. Modest decreases in [3H]glutamate and [3H]MK-801 binding were seen in several regions of hippocampus, and parietal and temporal cortex at early times after reperfusion, with values returning toward control by 24 h. In the striatum, a different pattern was seen: [3H]glutamate and [3H]MK-801 binding increased 50-200% at 0.5-4 h after the start of reperfusion, returning toward control levels by 24 h. These increases correlate with findings of increased sensitivity to NMDA-stimulated release of dopamine from striatal tissue in the same model (Werling et al., 1993), and suggest that changes in tissue receptors may contribute to the selective vulnerability to ischemic damage during the first hours following reperfusion.
Mol Chem Neuropathol
PMID:Global cerebral ischemia and reperfusion alters NMDA receptor binding in canine brain. 913 27


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