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)

Angiotensin II plays a pathophysiological role for the development of cardiovascular disease. Angiotensin receptor blocker(ARB) is an antihypertensive drug that blocks the angiotensin II receptor. Recently, according to the reports of basic research, ARB has various cerebrovascular-protective-effects such as improvement of cerebrovascular auto-regulation, stroke prevention, reduction of brain edema, improvement of neurological outcome in cerebral ischemia and so on. There is no report of ARB being used for the acute stage of stroke. In an ongoing ACCESS(Acute Candesartan Cilexetil Evaluation in Stroke Survivors) trial, the ARB candesartan is being used to treat the acute stage of stroke. This trial is expected to clarify whether early treatment with candesartan during the acute stage of stroke is beneficial for the neurological outcome or prognosis.
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PMID:[Beneficial effect of ARB for ischemic stroke]. 1239 96

To investigate whether the phosphorylation of p38 in cerebral ischemia occurs via angiotensin II receptor type 1a (AT1a), we examined the time course of phosphorylation of p38 and proline-rich tyrosine kinase 2 in AT1a knock-out mouse striatal neurons during middle cerebral artery occlusion (MCAO) and reperfusion. Phosphorylated-p38 was observed after 2 h and 5 h of reperfusion after 1 h of MCAO in C57/B6 mice and AT1a knock out mice, respectively. We demonstrated a delay of phosphorylation of p38 in the reperfusion model of the AT1a knock-out mouse, and detected microglia in the striatum on the ischemic side that were phosphorylated-p38-positive after 71 h of reperfusion in both animals. However, there was no association between AT1a and delayed neuronal cell death, or between AT1a and activation of caspase-9 in cerebral ischemia/reperfusion.
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PMID:Delayed phosphorylation of p38 mitogen-activated protein kinase in the AT1a knock-out mouse striatal neurons during middle cerebral artery occlusion and reperfusion. 1267 31

The mechanism behind the positive response to the inhibition of the angiotensin II receptor AT(1) in conjunction with stroke is elusive. Here we demonstrate that cerebrovascular AT(1) receptors show increased expression (upregulation) after cerebral ischemia via enhanced translation. This enhanced expression of AT(1) receptors occurs in the ischemic cerebral arteries and microvessels, and their inhibition results in a reduction in infarct volume. These findings add to the understanding of the vascular component in stroke, and the identified inhibition provides a new way to reduce the extent of cerebral ischemic damage.
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PMID:Cerebrovascular angiotensin AT1 receptor regulation in cerebral ischemia. 1843 48

The present study was designed to test pretreatment multiple doses of irbesartan (IRB) 50 mg, aspirin (ASP) 100 mg and the combination of both drugs for 7 days on middle cerebral artery-occluded (MCAO) rats. Focal cerebral ischemia was induced by MCA occlusion for 2 hours followed by reperfusion for 22 hours. After 24 hours of ischemia, grip strength and locomotor activity tests were performed. Animals were immediately sacrificed, infarct volume was measured followed by the estimation of markers of oxidative stress in the whole brains. Locomotor activity and grip strength were improved in IRB- and ASP-treated rats. Infarct volume was reduced in both IRB and ASP pretreatment as compared with MCAO rats. An elevation of thiobarbituric acid reactive substance (TBARS) and a reduction in glutathione (GSH) and antioxidant enzymes viz. superoxide dismutase (SOD) and catalase were observed following MCAO. Pretreatment of IRB and ASP showed the reduction in TBARS, elevation in GSH, SOD and catalase levels as compared with MCAO rats. The protective effects of IRB, an angiotensin II receptor antagonist having affinity for AT(1) receptor subtypes, could be due to inhibition of AT( 1) receptor expression in addition to its neuroprotective and free radical scavenging properties in cerebral ischemia. Further, it may be possible that the combination of IRB and ASP may be useful as an add-on therapy and would yield beneficial effects, if administered immediately following the ischemia in reducing the severity of the neurological deficits. However, our results are preliminary, further studies with posttreatment of IRB and ASP are required to provide more firm view.
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PMID:Protective effect of irbesartan, an angiotensin II receptor antagonist, alone and in combination with aspirin on middle cerebral artery occlusion model of focal cerebral ischemia in rats. 2048 39

OBJECTIVE Renin-angiotensin system (RAS) genetic polymorphisms are thought to play a role in cerebral aneurysm formation and rupture. The Cerebral Aneurysm Renin Angiotensin System (CARAS) study prospectively evaluated associations of common RAS polymorphisms and clinical course after aneurysmal subarachnoid hemorrhage (aSAH). METHODS The CARAS study prospectively enrolled aSAH patients at 2 academic centers in the United States. A blood sample was obtained from all patients for genetic evaluation and measurement of plasma angiotensin converting enzyme (ACE) concentration. Common RAS polymorphisms were detected using 5'exonuclease genotyping assays and pyrosequencing. Analysis of associations of RAS polymorphisms and clinical course after aSAH were performed. RESULTS A total of 166 patients were screened, and 149 aSAH patients were included for analysis. A recessive effect of allele I (insertion) of the ACE I/D (insertion/deletion) polymorphism was identified for Hunt and Hess grade in all patients (OR 2.76, 95% CI 1.17-6.50; p = 0.0206) with subsequent poor functional outcome. There was a similar effect on delayed cerebral ischemia (DCI) in patients 55 years or younger (OR 3.63, 95% CI 1.04-12.7; p = 0.0439). In patients older than 55 years, there was a recessive effect of allele A of the angiotensin II receptor Type 2 (AT2) A/C single nucleotide polymorphism (SNP) on DCI (OR 4.70, 95% CI 1.43-15.4; p = 0.0111). CONCLUSIONS Both the ACE I/D polymorphism and the AT2 A/C single nucleotide polymorphism were associated with an age-dependent risk of delayed cerebral ischemia, whereas only the ACE I/D polymorphism was associated with poor clinical grade at presentation. Further studies are required to elucidate the relevant pathophysiology and its potential implication in the treatment of patients with aSAH.
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PMID:Associations of renin-angiotensin system genetic polymorphisms and clinical course after aneurysmal subarachnoid hemorrhage. 2728 37