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

1. Injection of serotonin (5-hydroxytryptamine) to rats, induced a dramatic fall in brain ATP level, accompanied by an increase in P(i). Concomitant to these changes, the activity of cytosolic phosphofructokinase, the rate-limiting enzyme of glycolysis, was significantly enhanced. Stimulation of anaerobic glycolysis was also reflected by a marked increase in lactate content in brain. 2. Brain glucose 1,6-bisphosphate level was decreased, whereas fructose 2,6-bisphosphate was unaffected by serotonin. 3. All these serotonin-induced changes in brain, which are characteristic for cerebral ischemia, were prevented by treatment with the calmodulin (CaM) antagonists, trifluoperazine or thioridazine. 4. Injection of serotonin also induced a marked elevation of plasma hemoglobin, reflecting lysed erythrocytes, which was also prevented by treatment with the CaM antagonists. 5. The present results suggest that CaM antagonists may be effective drugs in treatment of many pathological conditions and diseases in which plasma serotonin levels are known to increase.
Gen Pharmacol 1994 Oct
PMID:Serotonin-induced decrease in brain ATP, stimulation of brain anaerobic glycolysis and elevation of plasma hemoglobin; the protective action of calmodulin antagonists. 787 54

1. Cerebral ischemia of 5 min duration was induced in unanesthetized gerbils by bilateral occlusion of the carotid arteries. 2. The extent of cerebral damage was assessed by the elevation of motor activity in comparison with control animals and by a histological assessment of the extent of neuronal degeneration in the CA1 area of the hippocampus. 3. Atropine, an antagonist of ACh, at either a low (1 mg/kg) or a high (10 mg/kg) dose administered 15 min prior to the ischemic episode, did not confer protection against cerebral ischemic damage. 4. This finding suggests that ACh does not play a critical role in the generation of ischemia reperfusion injury.
Gen Pharmacol 1994 Jul
PMID:Atropine and cerebral ischemic injury in the Mongolian gerbil. 795 34

1. The effects of KB-2796, a new diphenylpiperazine calcium antagonist, on the mitochondrial dysfunction and energy metabolism deficits were examined in the ischemic rat brain. 2. KB-2796 (30 mg/kg, p.o.), administered 60 min prior to decapitation, improved the reduced respiratory activity of mitochondria obtained from rat brain 5 min after decapitative ischemia. 3. KB-2796 (30 mg/kg, p.o.), administered 60 min prior to ischemic insult, improved both the reductions in pyruvate and ATP and prevented increases in the lactate/pyruvate ratio induced by 30-min forebrain ischemia in rats with 4-vessel occlusion (4-VO). 4. The effect of KB-2796 on local cerebral glucose utilization (LCGU) was examined by a quantitative autoradiographic 2-[14C]deoxyglucose method in normal and 4-VO rats. 5. Postischemic LCGU measured 24 hr after reperfusion in the forebrain, in particular in the cortex, thalamus, geniculate body, hippocampus, caudate-putamen, nucleus accumbens, colliculus, and corpus callosum, was below the normal control value. 6. KB-2796 (1 mg/kg, i.v.), administered 1 min prior to the injection of 2-[14C]deoxyglucose, improved the reductions in LCGU that were produced by cerebral ischemia in the cortex, thalamus, geniculate body, caudate-putamen, nucleus accumbens and substantia nigra, but did not affect LCGU in normal rats. 7. These findings suggest that KB-2796 minimized the deficits in brain energy metabolism produced by ischemia; this agent may therefore be a valuable therapeutic drug in cerebrovascular-related disorders.
Gen Pharmacol 1993 Nov
PMID:Effects of a new diphenylpiperazine calcium antagonist, KB-2796, on cerebral ischemic neuronal damage in rats. 811 23

1. We investigated alterations in dopamine D1 receptors in the striatum and hippocampus after transient cerebral ischemia in gerbils using [3H]SCH 23390 autoradiography. 2. We also examined the effect of vinconate against the alterations in dopamine D1 receptors after transient ischemia. 3. Transient ischemia was induced for 10 min, and vinconate (100 and 300 mg/kg) was given intraperitoneally 10 min before ischemia. 4. [3H]SCH 23390 binding showed no significant alterations in the striatum and hippocampus 5 hr after ischemia, whereas severe reduction in these areas was found after 7 days of recirculation. 5. Vinconate showed no significant alterations in [3H]SCH 23390 binding in the striatum and hippocampus except for a decrease in the hippocampal CA3 sector and dentate gyrus 5 hr after ischemia. By contrast, vinconate prevented a significant reduction in [3H]SCH 23390 binding in the striatum, hippocampal CA3 sector, hilus, and dentate gyrus 7 days after ischemia. 6. Vinconate inhibited lipid peroxidation in rat brain homogenates in a concentration-related manner. 7. These results indicate that free radicals generated from abnormal dopamine metabolism may play a key role in the development of ischemic brain damage. Furthermore, they suggest that vinconate prevents ischemic brain damage by inhibiting lipid peroxidation.
Gen Pharmacol 1993 Jan
PMID:Neuroprotective effect of vinconate against postischemic alterations in binding of [3H]SCH 23390 in the gerbil brain. 848 99

1. The adenosine A1 receptor enhancer, PD 81,723, was tested for its neuroprotective activity in a Mongolian gerbil model of forebrain ischemia/reperfusion cerebral ischemia. 2. Gerbils were injected with PD 81,723 (1, 10 and 125 mg/kg i.p.) 20 min before a 5-min episode of forebrain ischemia. The extent of ischemic injury was assessed by monitoring the increases in locomotor activity and from the degree of damage to the CA1 hippocampal pyramidal cell layer after 5 days of recovery. 3. By both criteria, PD 81,723, at all three dose levels, failed to protect against ischemia/reperfusion evoked cerebral injury.
Gen Pharmacol 1995 Nov
PMID:Adenosine A1 receptor enhancer, PD 81,723, and cerebral ischemia/reperfusion injury in the gerbil. 869 Feb 43

This investigation was undertaken to study the effect of iloprost, a stable analogue of prostacyclin, on infarct size after permanent focal cerebral ischemia in the rabbit. Forty-two adult rabbits were subjected to left middle cerebral artery occlusion via the transorbital route. Fourteen rabbits received an intravenous (i.v.) infusion of 30 micrograms/kg iloprost, 7 rabbits received an i.v. infusion of 10 micrograms/ kg, and 9 rabbits received an i.v. infusion of 20 micrograms/kg iloprost. Twelve rabbits received an intravenous infusion of saline. Treatment with iloprost started immediately after middle cerebral artery occlusion and continued for 1 h. After killing the animals, brains were removed and five coronal slices were incubated in a 2,3,5-triphenyltetrazolium chloride solution to determine the infarct size. Treatment with 30 micrograms/kg iloprost significantly reduced the infarct size compared with treatment with saline (3.49 +/- 2.79% vs. 9.03 +/- 4.26%, P < 0.001), but the lower doses of iloprost did not have a beneficial effect on the size of the infarct. These results suggest that intravenous iloprost treatment after occlusion has a highly protective effect without any side effects such as hypotension.
Gen Pharmacol 1996 Oct
PMID:Effect of the prostacyclin analogue, iloprost, on infarct size after permanent focal cerebral ischemia. 898 Oct 62

1. Remacemide hydrochloride has been shown to possess anticonvulsant activity in a wide range of animal models of epilepsy with ED50s in the 6-60 mg/kg range, depending on the species and route of administration. The compound also has been shown to be effective clinically as add-on therapy for partial seizures. 2. Degradation of remacemide yields the desglycinated metabolite that is approximately 2-fold more potent as an anticonvulsant agent than the parent drug. 3. Both compounds displace [3H]MK801 binding from the cerebral cortical membranes, and the metabolite is approximately 150-fold more potent in doing so than remacemide. This effect, together with the findings that the desglycinate reduces N-methyl-D-aspartate (NMDA)-induced depolarizations in a variety of preparations, suggests that the mechanism of action is through blockade of the channel site of the NMDA-receptor complex. 4. Remacemide and its metabolite, in common with other antiepileptic agents, block sustained repetitive-firing in cultured neurons. The metabolite also has been shown to decrease glutamate release from cortical slices. 5. Remacemide hydrochloride has neuroprotective properties when tested on models of cerebral ischemia. 6. The drug has low toxicity in contrast to other NMDA-channel-blocking compounds, such as MK801 and phencyclidine, probably because of its low affinity for the channel-binding site.
Gen Pharmacol 1997 Apr
PMID:Remacemide hydrochloride: a novel antiepileptic agent. 914 15

1. Human stroke is a complex and heterogeneous phenomenon that may defy attempts to develop a unitary animal model with which to address all of the relevant issues. 2. Focal models are regarded by many to be the approach of choice, but both global and focal models of cerebral ischemia can be sources of useful and complementary insight. 3. Of the global models, four-vessel occlusion requires a preparatory operative procedure that may increase the risk of extraneous factors confounding the response to the ischemic insult itself. The procedures are only partly reversible, with the vertebral arteries remaining permanently occluded. 4. The two-vessel occlusion model is easier to perform in a single procedure, and the less-intrusive surgical intervention allows greater scope for recovery experiments. The occlusion is fully reversible. 5. Many classes of compounds with therapeutic potential have been identified in the laboratory, often on the basis of success in one class of animal model, but translating these successes into a clinical context has proved singularly difficult. If, in future, compounds of interest are tested across a range of the available models, the likelihood of subsequent clinical success may be enhanced.
Gen Pharmacol 1998 Apr
PMID:Rodent models of global cerebral ischemia: a comparison of two-vessel occlusion and four-vessel occlusion. 952 58

The effect of transient cerebral ischemia on acetylcholinesterase (AChE) synthesis was studied in rats by a modified pharmacohistochemical method. The procedure involved in vivo irreversible inhibition of AChE by administration of the inhibitor diisopropyl fluorophosphate (DFP; 1.2 mg/kg b.w., i.m.) 1 h before 30 min forebrain ischemia (the four-vessel occlusion model). At the onset of ischemia, 70-75% of AChE was inhibited in the brain. Recirculation was followed by histochemical and biochemical investigations of newly synthesized AChE in the striatum, septum, cortex and hippocampus. Control sham-operated animals were treated with the same dose of DFP. For correlation, rats not treated with DFP were subjected to the same ischemic procedures and investigated simultaneously. In these rats, significant decrease in AChE activity was found in the striatum, septum and hippocampus during 24 h recirculation. In DFP treated rats, ischemia markedly depressed resynthesis of AChE; after 4 h recirculation, AChE activity was decreased by 45-60% in all investigated areas in comparison with controls and the AChE histochemistry showed only slightly stained neurons in the striatum and septum. Twenty-four hours after ischemia, these neurons were densely stained and the increase in AChE activity indicated a partial recovery of the enzyme synthesis. These results suggest that the depression of AChE synthesis after forebrain ischemia is probably transient, not accompanied by cholinergic neuron degeneration.
Gen Physiol Biophys 1999 Mar
PMID:Depression of acetylcholinesterase synthesis following transient cerebral ischemia in rat: pharmacohistochemical and biochemical investigation. 1037 21

Possible correlation of M/T polymorphism of angiotensinogen gene with risk of ischemic stroke and basic risk factors of cerebral pathology (levels of arterial pressure and blood cholesterol; presence of diabetes mellitus, coronary heart disease, or myocardial infarction in anamnesis; and stenosis of major cerebral arteries) was studied. It was shown that M/T polymorphic variants of angiotensinogen gene were factors determining neither clinical variant of cerebral ischemia development (acute ischemic stroke or chronic brain ischemia) nor formation of main risk factors of stroke.
Mol Gen Mikrobiol Virusol 2003
PMID:[Role of missense mutation (M235T) in the angiotensinogen gene in development of cerebral ischemia]. 1265 48


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