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)

Excessive activation of glutamate receptors, most notably the N-methyl-D-aspartate (NMDA) subtype, appears to be a crucial factor in the sequence of cellular events which lead to irreversible ischaemic damage to neurones. The ability of newly developed antagonists of the NMDA receptor to reduce ischaemic brain damage has been assessed in cat and rodent models of focal cerebral ischemia. Non-competitive NMDA receptor antagonists such as dizocilpine (CAS 77086-21-6) which act at a site within the receptor operated ion channel markedly reduce (by more than 50%) ischaemic brain damage when administered prior to the ischaemic episode or 2 h after the onset of ischaemia. Competitive NMDA receptor antagonists, such as D-(E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid, which act at the neurotransmitter recognition site are equally effective in reducing the ischaemic brain damage when administered prior to the onset of the ischaemic episode. The clinical utility of competitive and non-competitive NMDA receptor antagonists in man will, however, be determined not by their tremendous anti-ischaemic efficacy, but by their profile of adverse effects. Careful selection of the therapeutic target for NMDA antagonists will be necessary if beneficial effects are to be established in man.
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PMID:Ischaemic brain damage--prevention with competitive and non-competitive antagonists of N-methyl-D-aspartate receptors. 183 Apr 83

E2001 (2-(4-(p-fluorobenzoyl)-piperidin-1-yl)-2'-acetonaphthone hydrochloride, CAS 107025-80-9) is a novel anti-ischemic agent, which is reported to protect against delayed neuronal death in the CA1 subfield of the hippocampus. The effect of E2001 on ischemia-induced impairment of the passive avoidance response in gerbils was studied. The passive avoidance response was not disturbed by transient cerebral ischemia of 3 min duration, but was impaired by 5-min ischemia. E2001 at oral doses of 3 and 10 mg/kg significantly improved the impaired passive avoidance response induced by 5-min cerebral ischemia. It is speculated that the improvement by E2001 may be partly due to the inhibition of extracellular glutamate accumulation, and the suppression of lipid peroxides formation during cerebral ischemia.
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PMID:Protective effect of the novel anti-ischemic agent 2-(4-(p-fluorobenzoyl)-piperidin-1-yl)-2'-acetonaphthone hydrochloride against ischemia-induced impairment of the passive avoidance response in gerbils. 209 25

4-(o-Benzylphenoxy)-N-methylbutylamine hydrochloride (bifemelane, CAS 90293-01-9, Celeport) has been reported to exert a protective effect on the brain against ischemic insults. However, the underlying mechanism of this action has not yet been fully elucidated. The effects of bifemelane on the intracellular pH (pHi) and energy metabolism of the ischemic brain were examined in Mongolian gerbils using in vivo 31P nuclear magnetic resonance spectroscopy. Transient global ischemia was produced by clipping both common carotid arteries for 45 min, and the brain was reperfused by releasing the clips. Bifemelane (10 or 20 mg/kg) or normal saline was administered intraperitoneally 30 min prior to the ischemia. During the ischemia, adenosine triphosphate (ATP) and phosphocreatine (PCr) were markedly reduced in association with an increase in inorganic phosphate (Pi) and decrease in pHi in both the control and bifemelane groups. The extents of energy disturbance and intracellular acidosis in the three groups were identical. After reperfusion, ATP, PCr, Pi and pHi recovered towards the pre-ischemic levels in all the groups. In the bifemelane groups, the recovery of pHi was significantly faster than in the control group. Of the two bifemelane groups, the 20 mg/kg group showed more excellent pHi recovery as compared to the 10 mg/kg group. The energy recovery in the three groups were almost identical, although the 20 mg/kg group showed some tendency towards faster recovery as compared to the control group. The present results suggest that bifemelane may accelerate recovery of the pHi after cerebral ischemia. Such an action may contribute to the cerebral protective effects of this drug against ischemic insults.
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PMID:Effect of bifemelane on the intracellular pH and energy state of the ischemic brain. 212 87

Effect of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H -1- benzopyran-6yl-hydrogen phosphate] potassium salt (EPC-K1, CAS 127061-56-7), a diester of alpha-tocopherol and ascorbic acid, on transient cerebral ischemia was studied in Mongolian gerbils. Cerebral energy metabolism and intracellular pH (pHi) were estimated employing in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Intraperitoneal injection of EPC-K1 (5 or 10 mg/kg) prior to ischemia significantly ameliorated pHi reduction in a dose dependent manner during ischemia. After reperfusion, energy and pHi recoveries were significantly faster in the EPC-K1 groups than in the control group. EPC-K1 (10 mg/kg) significantly reduced the extent of cerebral edema. Moreover, administration of EPC-K1 immediately after reperfusion significantly shortened the consciousness recovery in a dose dependent manner. The results suggest that EPC-K1 may exert protective effects on ischemic brain and may have therapeutic value in ischemic stroke.
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PMID:Effects of L-ascorbic acid 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1- benzopyran-6yl-hydrogen phosphate] potassium salt on cerebral energy state and consciousness recovery following transient forebrain ischemia in gerbils. 798 54

In this study the effect of post-ischemic treatment of AJ-3941 ((+/-)-(E)-1-(3-fluoro-6,11-dihydrodibenz [b,e]-oxepine-11-yl)-4-(3-phenyl-2-propenyl)-piperazine dimaleate, CAS 143110-70-7) a cerebrovascular-selective calcium antagonist, on brain infarction and edema in a rat model of focal cerebral ischemia with permanent middle cerebral artery occlusion (MCAo) was evaluated. Brain infarct size was determined at 24 h after MCAo by measuring 2,3,5-triphenyltetrazolium chloride-negative stained area of the serial brain sections. Post-ischemic treatment of AJ-3941 (3 mg/kg p.o.), 10 min and 3 h after the insult, significantly reduced brain infarct size by 44-80%, compared to vehicle control. The reducing effect was observed both in the cortical and subcortical regions. Three days after MCAo, contents of water and Na+ in the ipsilateral hemisphere significantly increased comparing with those in control rats. Post-ischemic treatment with AJ-3941 (3 and 10 mg/kg twice daily p.o. for 2 days) markedly inhibited the increase in water content and suppressed the increase in Na+ content. In the contralateral hemisphere, these contents showed no significant differences between vehicle-treated group and either control (non-operated) or AJ-3941-treated group. AJ-3941 had only minimum effect on body temperature and physiological parameters, such as blood pressure, blood gases and glucose, even when the maximum dose used (10 mg/kg) was repeatedly administered. These results indicate that post-ischemic treatment with AJ-3941 may ameliorate the brain infarction and edema after permanent focal cerebral ischemia, and they also suggest that AJ-3941 has a beneficial effect in the treatment of ischemic cerebral damage.
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PMID:Protective effect of the novel cerebrovascular-selective calcium antagonist (+/-)-(E)-1-(3-fluoro-6, 11-dihydrodibenz[b,e]-oxepine-11-yl)-4-(3-phenyl-2-propenyl)-piperazine dimaleate on ischemic brain damage after permanent middle cerebral artery occlusion in rats. 876 45

Effect of the new competitive N-methyl-D-aspartate (NMDA) antagonist D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CAS 137424-81-8, CGP 40116) was examined in a mongolian gerbil model of global cerebral ischemia. Effect of CGP 40116 was compared to that of another competitive NMDA antagonist, (+/-)-cis-4-phosphonomethyl-piperadine-2-carboxylic acid (CAS 110347-85-8, CGS 19755) under the same conditions. Drugs were administered intraperitoneally 30 min before bilateral carotid artery occlusion. At 4 days after the ischemia, locomotor activity was significantly higher in ischemic control mongolian gerbils in comparison with sham-operated mongolian gerbils. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the doses of 10 and 30 mg/kg significantly suppressed the increase of the motility. Seven days after ischemia, ischemic control group was still hyperactive compared to sham-operated group. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the dose of 30 mg/kg significantly reversed it. The number of survived neurons of ischemic control group was significantly less than that of sham-operated group at 7 days after ischemia. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the dose of 30 mg/kg significantly increased the number of survived neurons. It is concluded that CGP 40116 is more potent for amelioration of global cerebral ischemic damage than CGS 19755.
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PMID:Neuroprotective effect of D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid in the gerbil model of transient global cerebral ischemia. 923 45

The effect of the new competitive N-methyl-D-aspartate (NMDA) antagonist D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CAS 137424-81-8, CGP 40116) was examined in a cat model of focal cerebral ischemia. Effect of CGP 40116 was compared to that of another competitive NMDA antagonist, (+/-)-cis-4-phosphonomethyl-piperadine-2-carboxylic acid (CAS 110347-85-8, CGS 19755) under the same conditions. Drugs were administered intravenously 30 min before left middle cerebral artery (MCA) occlusion. After MCA occlusion for 8 h, infarction spreaded widely among caudate nucleus prepyriform cortex, amygdala and temporal lobe cortex in the ischemic hemisphere. CGP 40116 at the dose of 10 mg/kg and CGS 19755 at the dose of 30 mg/kg significantly decreased the infarcted area. CGP 40116 was effective in the frontal and central brain, although CGS 19755 showed neuroprotective effect in almost all sites. Thus, the compounds are potent neuroprotectants in focal ischemia.
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PMID:Effect of D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid on focal cerebral ischemia in cat. 923 46

The efficacy of post-ischemic treatment with AJ-3941 ((+/-)-(E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]-oxepine-11-yl )-4-(3-phenyl-2- propenyl)-piperazine dimaleate, CAS 143110-70-7), a cerebrovascular selective Ca2+ channel antagonist, on brain infarction induced by focal ischemia-reperfusion in rats was evaluated. Focal ischemia was induced by transient occlusion of middle cerebral artery (MCA) with a 3-0 nylon monofilament for 90 min. One day after MCA occlusion (MCAo), brain infarct size was determined by measuring 2,3,5-triphenyltetrazonium chloride-negative stained area of the serial brain sections. The development of cerebral infarction was observed in both regions of cortex and subcortex, such as striatum, caudatum, putamen, hippocampus and corpus callosum. Post-ischemic treatment with AJ-3941 (1 or 3 mg/kg p.o., 10 min and 3 h after the occlusion) significantly reduced the infarct size and volume in the ipsilateral hemisphere in a dose-dependent manner, compared to the solvent control. The reducing effect was observed mainly in the cortical region, and a significant reduction of the subcortical infarct volume was found at the higher dose (3 mg/kg). Post-ischemic treatment with the thromboxane A2 synthetase inhibitor, sodium ozagrel (150 micrograms/kg/min i.v. infusion, between 1 h and 24 h after the MCAo) did not reduce the infarct volume in the hemisphere after ischemia-reperfusion. AJ-3941 had only minimum effect on the elevation of body temperature during ischemia-reperfusion. These results indicate that post-ischemic treatment with AJ-3941 may ameliorate the brain injury after the transient focal cerebral ischemia, and they suggest that AJ-3941 has beneficial effects for treatment of ischemic cerebral damage, such as stroke.
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PMID:Post-treatment of transient focal cerebral ischemia in rats with the novel cerebrovascular-selective Ca2+ channel antagonist (+/-)-(E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]-oxepine-11-yl)-4-(3-pheny l-2-propenyl)-piperazine dimaleate. 927 34

In vivo magnetic resonance imaging was used to study the effect of ancrod (CAS 9046-56-4, Arwin), a plasma fibrinogen level lowering agent, on brain lesion in two rat models of acute focal cerebral ischaemia. Total lesion volume was determined by multislice T2-weighted magnetic resonance imaging 24 h after permanent middle cerebral artery occlusion. Intravenous infusion of ancrod starting 30 min after middle cerebral artery occlusion at dosages of 10, 30, 50 or 70 IU/kg (n = 9/group) significantly diminished cerebral lesion volume by 20 to 33% as compared to vehicle-infused controls (n = 12). None of the ancrod-treated rats showed evidence of intracerebral bleeding on T2-weighted magnetic resonance images taken after 24 h. In photochemically induced (rose bengal) unilateral thrombotic cortical infarction brain damage was displayed by multislice diffusion-weighted magnetic resonance imaging after 24 h. Again, post treatment with ancrod reduced total volume of cerebral lesion dose-dependently from 142 +/- 28 mm3 in the controls (n = 10) to 121 +/- 28 mm3 (n = 10) and 111 +/- 20 mm3 (n = 11, p < 0.05) in rats treated with 10 and 30 IU/kg ancrod, respectively (means +/- S.D.). These results suggest cerebroprotection in focal cerebral ischaemia by improvements in the cerebral microcirculation which may offer a potential and safe approach for therapy of acute stroke.
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PMID:Magnetic resonance imaging studies on the effect of the fibrinogen-lowering agent ancrod on cerebral lesions in two rat models of acute stroke. 929 73

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


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