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

Repeatedly bred male rats which develop arteriosclerosis spontaneously were subjected to unilateral nephrectomy, 1% saline drinking water, and 2 mg subcutaneous injections of deoxycorticosterone acetate per animal weekly for 7 weeks to induce severe hypertension (+/- 175 mmHg systolic). Acute cerebral ischemia was induced by ligating one carotid artery. Two days later, experimental animals were subjected to acute myocardial ischemia by injecting them subcutaneously with a single dose of isoproterenol (25 mg/100 g body weight). All of the experimental animals died within 4 hours of the injection of isoproterenol. During this same period, blood pressure, body weight, thymus, kidney, and testicular weights were reduced, whereas heart and adrenal gland weights increased markedly. Serum enzymes (CPK, SGOT, and LDH), lipids (triglycerides and free fatty acids), glucose, BUN, and corticosterone rose progressively. Fatty infiltration of the liver, adrenal hyperplasia, myocardial thrombi, renal degenerative changes, and cerebral edema became progressively more severe. A hypothalamic-pituitary-adrenal axis component may be involved in the reaction to the stress of acute cerebral or myocardial ischemia, which is intensified when the two ischemias are combined, and chronic hypertension may exacerbate both.
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PMID:Acute cerebrovascular and myocardial ischemia superimposed upon chronically hypertensive and arteriosclerotic male Sprague-Dawley rats. 90 14

Male and female, arteriosclerotic (breeder) and nonarteriosclerotic (virgin), Sprague-Dawley rats were made severely diabetic with alloxan. Two weeks later experimental animals had both carotid arteries ligated to induce a state of acute cerebral ischemia. After six weeks of cerebral ischemia either with or without severe diabetes the animals were killed. Animals which survived either the acute induction of diabetes or cerebral ischemia did not manifest any new episodes of cerebral ischemia. Subjects with combined diabetes and cerebral ischemia manifested the greatest loss in body weight, adrenal hypertrophy and thymus gland involution, increased levels of serum CPK and SGOT, but decreased SGPT and LDH, hyperglycemia and hypertriglyceridemia, and the most extensive cerebral edema. It is suggested that diabetic rats may have a greater predilection toward cerebrovascular accidents because the diabetic state contributes not only to an exacerbation of atherosclerosis, but also complicates any condition of cerebrovascular ischemia by creating extracerebral edema.
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PMID:Chronic diabetes followed by chronic cerebral ischemia induced by bilateral carotid artery ligation in arteriosclerotic versus nonarteriosclerotic rats. 117 43

Three different pressure groups of rats, stroke-prone spontaneously hypertensive rats (SHRSP, 200-270 mmHg), stroke-resistant SHR (SHRSR, 160-240 mmHg), and Wistar rats (WR, 120-160 mmHg) were used to investigate the effect of prior existing hypertension on the severity of brain damage induced by ischemia. The cerebral ischemia was induced by bilateral common carotid artery ligation (BLCL) and the survival rate, cerebral blood flow, cerebral energy metabolites (ATP, lactate c-AMP) and water content were measured. Colloidal carbon perfusion was also performed. Sixteen-week-old male rats were used. The survival rate was observed until 24 hours after BLCL. Cerebral blood flow was measured in parietal cortex by hydrogen clearance method. ATP was measured by luciferin-luciferase method, and lactate by enzymatic method using LDH. c-AMP was measured by radioimmunoassay. Brain water content was measured by freeze-dry method. These measurements were done for animals surviving 6 hours of BLCL. Colloidal carbon perfusion was done according to Ames' Method. The survival rate was lower in the hypertension group. The survival of SHRSP and SHRSR were 20% compared to 71% in WR after 24 hours of BLCL. The cerebral circulation of SHRSP fell abruptly and was near to zero after one hour of BLCL. In SHRSR this fall of cerebral blood flow was prominent in the rats of higher blood pressure. On the other hand there was no apparent fall of cerebral blood flow in WR after BLCL. The cerebral energy metabolites. ATP and c-AMP showed the lowest level in SHRSP which had the negative correlation to blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Experimental cerebral ischemia after bilateral common carotid artery ligation in SHRSP, SHRSR and Wistar rats: correlation between blood pressure and degree of ischemia]. 609 92

Male and female, spontaneously hypertensive rats (SHR) with blood pressures ranging from 190-210 mmHg were subjected unilateral or bilateral carotid artery ligation. Representative numbers of animals were killed 2, 4, 6, 8, 10, 12, 24 and 48 hours later. Severe cerebral ischemia caused a significant and protracted increase in the pre-existent high blood pressure, the enzymes CPK, SGOT and LDH triglycerides, free fatty acids, glucose, and corticosterone. Despite these marked pathophysiologic changes, the brains of these animals were free of real damage except for cerebral edema and scattered petechiae. Some of the animals developed massive atrial thrombi and myocardial infarcts. It is suggested that severe cerebral ischemia precipitated the myocardial infarcts through the aegis of the hypothalamic-pituitary-adrenal stress response.
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PMID:Comparative effects of unilateral and bilateral carotid artery ligation in the spontaneously hypertensive rat. 735 34

In order to evaluate the clinical and prognostic significance of early hyperfibrinogenemia in patients with transient ischemic attack (TIA) and ischemic cerebral infarction (ICI), we analyzed the relationships between plasma fibrinogen, brain damage severity, clinical status on admission and intra-hospital mortality. Vascular damage severity was estimated by measuring the necrotic area by computed axial tomography (CT) and indirectly by means of changes in some plasma enzymes (CK, LDH, GPT/ALT, and GOT/AST). Plasma fibrinogen levels were statistically higher in ICI than in TIA and control subjects (p < 0.0005; analysis of variance). Moreover, plasma fibrinogen was directly related to the extension of the necrotic area at CT scan (p < 0.05) and in ICI patients was positively correlated with CK (r = 0.50, p < 0.01), LDH (r = 0.41, p < 0.05) and GOT/AST (r = 0.42, p < 0.05) serum levels, but not with GPT/ALT. A higher plasma fibrinogen value was observed in patients with stupor or coma compared with those with alert consciousness (p < 0.05). In patients who died during hospitalization, fibrinogen levels were higher than those of subjects who were discharged (p < 0.005). The results indicate that in the early phase of cerebral ischemia, plasma fibrinogen levels are related to the severity of the clinical status and to the extension of the brain vascular damage, thus representing a negative clinical and prognostic factor of the disease.
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PMID:Clinical and prognostic significance of hyperfibrinogenemia in cerebral ischemia. 986 53

Focal cerebral ischemia activates the nuclear protein poly(ADP-ribose) polymerase (PARP) by single DNA strand breaks which leads to energy depletion and cell necrosis. Deletion or inhibition of PARP protects against ischemic brain injury. Here we examined the neuroprotective effect of PJ34, a novel potent inhibitor of PARP in vitro and in vivo. Serum-free primary neuronal cultures derived from rat cortex (E15-17) and kept in culture for 10 days were exposed to oxygen glucose deprivation (OGD) in vitro. Neuronal injury was quantified by LDH release after 24 h. Pretreatment with 30-1000 nM PJ34 significantly protected from OGD-induced cell injury in a dose-dependent manner. For in vivo experiments SV/129 mice were treated with PJ34 (50 microg) by intraperitoneal injection 2 h before 1 h middle cerebral artery occlusion (MCAo) and again 6 h later. Twenty-three h after reperfusion ischemic injury was significantly decreased compared to vehicle-treated controls (infarct volume reduction of 40%, p<0.05). Similarly, in a rat model of MCAo (2 h occlusion followed by up to 22 h reperfusion), PJ34 administration (10 mg/kg i.v.) significantly reduced infarct size, and the effect of the drug was maintained even if it was given as late as 10 min prior to reperfusion time. PJ34 significantly protected in a 4 h, but not in a 24 h permanent occlusion model. In conclusion, PJ34, a novel, potent inhibitor of PARP exerts massive neuroprotective agents, with a significant therapeutic window of opportunity. The present work strengthens the concept that pharmacological PARP inhibition may be a suitable approach for the treatment of acute stroke in man.
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PMID:Protective effects of PJ34, a novel, potent inhibitor of poly(ADP-ribose) polymerase (PARP) in in vitro and in vivo models of stroke. 1117 3

The antioxidant effect of the non-specific nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (CAS 50903-99-6, L-NAME), was studied in a rat model of global cerebral ischemia. In addition, the influence of low doses of L-NAME on nitric oxide production, measured as nitrate/nitrite end products, was investigated in the ischemic rats. Ischemia was induced by bilateral clamping of the common carotid arteries for 60 min followed by a reperfusion period for 60 min. L-NAME was administered intraperitoneally in the doses of 1 and 3 mg kg-1, twice, immediately after ischemia and 15 min before termination of the experiment. The drug decreased the elevated activity of lactate dehydrogenase (LDH, 1.1.1.27) as well as the increased level of lipid peroxide in the rat brain. L-NAME was also capable to normalize the reduced activity of superoxide dismutase (SOD, 1.15.1.1) that was observed after ischemia. Improvement of these parameters in L-NAME-treated rats was parallel to normalization of nitric oxide production in the treated animals. These results indicate that inhibition of nitric oxide synthase, induced by L-NAME, could improve the oxidative status of the rat brain after ischemia.
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PMID:Antioxidant effect of N omega-nitro-L-arginine methyl ester (L-NAME) on global cerebral ischemia in a rat model. 1155 22

Previous work has shown that hydroxysafflor yellow A (HSYA), extracted from Carthamus tinctorius L. markedly extended the coagulation time in mice and exhibited a significant antithrombotic effect in rats. The present study was conducted to demonstrate further its neuroprotective effects on cerebral ischemic injury in both in vivo and in vitro studies. In vivo, male Wistar-Kyoto (WKY) rats with middle cerebral artery occlusion (MCAO) were evaluated for neurological deficit scores followed by the treatment with a single dose of HSYA. Furthermore, the infarction area of the brain was assessed in the brain slices. In vitro, the effect of HSYA was tested in cultured fetal cortical cells exposed to glutamate and sodium cyanide (NaCN) to identify its neuroprotection against neurons damage. The results in vivo showed that sublingular vein injection of HSYA at doses of 3.0 mg/kg and 6.0 mg/kg exerted significant neuroprotective effects on rats with focal cerebral ischemic injury by significantly decreasing neurological deficit scores and reducing the infarct area compared with the saline group, HSYA at a dose of 6.0 mg/kg showed a similar potency as nimodipine at a dose of 0.2 mg/kg. Sublingular vein injection of HSYA at the dose of 1.5 mg/kg showed a neuroprotective effect, however, with no significant difference when compared with the saline group. Results in vitro showed that HSYA significantly inhibited neuron damage induced by exposure to glutamate and sodium cyanide (NaCN) in cultured fetal cortical cells. Noticeably, the neuroprotective action of HSYA on glutamate-mediated neuron injury was much better than that of HSYA on NaCN-induced neuron damage. All these findings suggest that HSYA might act as a potential neuroprotective agent useful in the treatment in focal cerebral ischemia. Abbreviations. HSYA:hydroxysafflor yellow A TTC:2,3,5-triphenyltetrazolium chloride MTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide DMEM:Dulbecco's modified Eagle medium FCS:Fetal calf serum MCAO:middle cerebral artery occlusion ECA:external carotid artery ICA:internal carotid artery LDH:lactate dehydrogenase NMDA: N-methyl- D-aspartate
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PMID:Neuroprotective effects of hydroxysafflor yellow A: in vivo and in vitro studies. 1280 24

Experiments were performed on male Wistar rats under nembutal-urethan anesthesia. Short-time (10 min) cerebral ischemia was induced by bilateral ligation of carotid arteries. This was followed by an increased synthesis of NO and activity of energy metabolism enzymes (SDH, LDH) in a part of neurons of the parietal cortex and in endotheliocytes of blood vessels. The ultrastructural changes of some neurons and synaptic formations indicated functional tension, while in the others the irreversible changes (disturbed lipid metabolism, destructive alterations of the nucleus and cytoplasm) were found.
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PMID:[Changes in the activity of NO-synthase, energy metabolism enzymes and ultrastructure in neurons of the cerebral cortex in the model of short-term ischemia]. 1294 22

Oxidative stress plays an important role in neuronal cell death associated with many different neurodegenerative conditions such as cerebral ischemia and Parkinson's disease. Elevated levels of glutamate are thought to be responsible for CNS disorders through various mechanisms causing oxidative stress induced by a nonreceptor-mediated oxidative pathway which blocks cystine uptake and results in depletion of intracellular glutathione (GSH). The newly designed amide form of N-acetylcysteine (NAC), N-acetylcysteine amide (NACA), was assessed for its ability to protect PC12 cells against oxidative toxicity induced by glutamate. NACA was shown to protect PC12 cells from glutamate (Glu) toxicity, as evaluated by LDH and MTS assays. NACA prevented glutamate-induced intracellular GSH loss. In addition, NACA restored GSH synthesis in a Glu (10 mM) plus buthionine-sulfoximine (BSO) (0.2 mM)-treated group, indicating that the intracellular GSH increase is independent of gamma-GSC (gamma-glutamylcysteinyl synthetase). The increase in levels of reactive oxygen species (ROS) induced by glutamate was significantly decreased by NACA. Measurement of malondialdehyde (MDA) showed that NACA reduced glutamate-induced elevations in levels of lipid peroxidation by-products. These results demonstrate that NACA can protect PC12 cells against glutamate cytotoxicity by inhibiting lipid peroxidation, and scavenging ROS, thus preserving intracellular GSH.
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PMID:Effects of N-acetylcysteine amide (NACA), a novel thiol antioxidant against glutamate-induced cytotoxicity in neuronal cell line PC12. 1612 Apr 36


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