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

The effects of nimodipine, a 1,4-dihydropyridine calcium channel blocker, on multiunit activity (MUA) of several brain structures were investigated in cats during 6 h immediately following acute global cerebral ischemia-anoxia induced by a 10 min cardiorespiratory arrest (CRA), as well as in cats exposed to sham procedures corresponding to CRA. Four groups of cats were studied: 1) CRA and continuous administration of nimodipine, 1 microgram/kg/min iv during 6 h; 2) CRA and continuous administration of vehicle; 3) sham and continuous administration of nimodipine as in group 1; 4) sham and vehicle as in group 2. MUA and electroencephalogram disappeared during ischemia-anoxia; their progressive recovery occurred throughout the hours following CRA, although 6 h after CRA MUA was still lower than its control prearrest values in all the recorded subcortical structures. Delta-like waves, isolated spikes, and bursts of fast EEG waves occurred during the recovery of EEG activity. Nimodipine inhibited the otherwise increasing MUA in mesencephalic reticular formation, hippocampus and putamen, but not in ventromedial hypothalamus, during the hours following acute global cerebral ischemia-anoxia. Absence of isolated spikes and bursts of fast EEG activity was noted in the EEG of CRA-, nimodipine-treated cats. Nimodipine significantly reduced MUA in hippocampus but not in other cerebral structures in cats of the sham treated group. The results suggest the involvement of 1,4 dihydropyridine sensitive calcium channels in the cellular mechanisms related to neuronal activity after cerebral ischemia-anoxia, and the possible relationship between the effects of nimodipine on MUA and better functional conditions of the central nervous system after acute global cerebral ischemia-anoxia.
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PMID:Effects of nimodipine on multiunit activity of several brain structures following acute global cerebral ischemia-anoxia in cats. 129 69

The role of calcium as a second messenger which mediates the transmission of the signal and has an impact on cellular regulation of the majority of organs at all stages of development was confirmed during the past decade. In the submitted review the authors summarize mechanisms by which calcium exerts its regulatory function. At the same time the authors discuss the possible ratio of disorders in the above systems in various diseases in particular those of the central nervous system and possible pharmacotherapeutic interferences at different levels of transmission of the signal mediated by calcium. As in the mentioned area at the clinical level so far mainly calcium channel blockers were used, the authors summarize the use of these substances in the treatment of cerebral ischaemia, migraine, epilepsy and manic-depressive disease.
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PMID:[Possibilities of therapeutic applications of neuronal calcium homeostasis]. 166 83

The effect of omega-conotoxin GVIA (CgTX), an N-and L-type voltage-sensitive calcium channel (VSCC) blocker, on the release of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum before and during transient cerebral ischemia in spontaneously hypertensive rats was studied using an in vivo brain dialysis technique. Continuous perfusion of CgTX in the striatum was started 20 min before ischemia and concentrations of dopamine and DOPAC in the dialysate were measured using HPLC with an electro-chemical detector. Before ischemia, both 10 and 100 microM CgTX significantly lowered the concentration of dopamine, to 49% of the basal values. DOPAC concentrations also decreased significantly, by 28 and 17%, respectively. Forebrain ischemia, produced by bilateral carotid artery occlusion, reduced striatal blood flow to less than 6% of the resting value in each group. During 20 min of ischemia, the vehicle group showed a marked increase in dopamine (175 times the basal concentration). In the 10 or 100 microM CgTX perfusion group, in contrast, dopamine release was significantly attenuated, to 38 or 29% of the vehicle group, respectively. DOPAC concentrations decreased during ischemia to 58% of the basal value in the vehicle group and 49% in both CgTX groups. These results indicate that the massive release of striatal dopamine during ischemia depends largely on the influx of extracellular calcium via CgTX-sensitive VSCCs.
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PMID:Inhibition of ischemia-induced dopamine release by omega-conotoxin, a calcium channel blocker, in the striatum of spontaneously hypertensive rats: in vivo brain dialysis study. 172 36

Approximately 10 in 100,000 persons suffer rupture of a saccular intracranial aneurysm annually, and roughly 60% of these will survive the initial catastrophe in reasonable neurological condition. Of the many ensuing complications of aneurysmal subarachnoid hemorrhage, the most frustrating continues to be a form of delayed-onset cerebral arterial narrowing known as vasospasm. Because it is caused by thick subarachnoid blood clots coating the adventitial surface of cerebral arteries, the distribution and severity of vasospasm correlates closely with location and volume of subarachnoid hematoma as visualized on computed tomography (CT). Critical vasospasm causes cerebral ischemia and infarction: the "second stroke." It is now know that vasospasm represents sustained arterial contraction rather than structural thickening of the vessel wall with lumen encroachment. A large body of evidence points to oxyhemoglobin, released from lysing erythrocytes, as the principal component of blood clot responsible for this contraction. The precise mechanism by which oxyhemoglobin causes prolonged vascular smooth muscle cell constriction has not yet been established, but possibilities include secondary generation of vasoactive free radicals, lipid peroxides, eicosanoids, bilirubin, and endothelin. Vasospasm treatments are directed at preventing or reversing arterial narrowing, or at preventing or reversing cerebral ischemia. Several treatments from the latter category, namely, hypertensive, hypervolemic hemodilutional therapy and the calcium channel blocker nimodipine, have proven moderately effective and are in widespread clinical use. It has also been possible to mechanically dilate vasospastic vessels with transluminal angioplasty improving cerebral blood flow to ischemic brain. However we are still in need of an effective agent to prevent arterial narrowing, and several hopeful candidates in this category of treatment are clot lytic agent tissue plasminogen activator (rt-PA) and an inhibitor of iron-dependent peroxidation, 21-aminosteroid U74006F (tirilazad mesylate).
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PMID:Current concepts of pathophysiology and management of cerebral vasospasm following aneurysmal subarachnoid hemorrhage. 177 40

Calcium ion functions widely as an intracellular messenger and regulator. Intracellular calcium dyshomeostasis occurs during hypoxic/ischemic cell injury, and pharmacological antagonism of calcium entry into neurons has been considered to be of potential therapeutic value. Calcium antagonists, in addition, tend to improve cerebral perfusion of both the normal and abnormal (post-ischemic) brain. Studies of these agents have shown variable degrees of cerebroprotection in focal and global ischemia models. (S)-Emopamil is a phenylalkylamine-type calcium channel blocker which also exhibits stereoselective antagonism of the serotonin S2 receptor and has excellent blood-brain barrier penetrability. Protection of hippocampal CA1 neurons has been demonstrated with pre-ischemic administration of (S)-emopamil in global ischemia models. Our laboratory has compared the efficacy of pre- vs. post-ischemic (S)-emopamil treatment on neuronal necrosis resulting from 10 min of transient normothermic global ischemia in the rat. (S)-Emopamil pre-treatment, 20 mg/kg i.p., 30 min prior to ischemia, with a second dose 2.5 h later, resulted in 1.8-2.4 fold increases in numbers of surviving CA1 pyramidal neurons. Post-ischemic administration was ineffective. Intracerebral microdialysis has revealed a partial attenuation of dopamine release with pre-ischemic (S)-emopamil administration. In focal cerebral ischemia (middle cerebral artery occlusion in the rat), our laboratory has demonstrated a marked reduction in cortical infarct volume with (S)-emopamil pre- or post-treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium antagonists in the treatment of experimental cerebral ischemia. 185 3

We report the binding characteristics of [3H]nimodipine to normal and ischemic brain in vivo. We used the 1,4-dihydropyridine, nimodipine, to label the L-type voltage-sensitive calcium channel in focal cerebral ischemia after occlusion of both the middle cerebral and ipsilateral common carotid arteries in rats. Varying concentrations of [3H]nimodipine were infused 3.5 h after the onset of ischemia and circulated for 30 min before the brain was obtained for autoradiography and determination of regional nimodipine content. In separate sets of experiments, the metabolites of nimodipine were determined and the conditions for equilibrium of nimodipine distribution were established. Increased nimodipine uptake was observed in ischemic regions. This increased binding was saturable and specific with an affinity constant, KD, of 0.45 nM and a maximal regional binding capacity, Bmax, ranging from 3.1 to 10.9 pmol/g. Only binding to ischemic tissue was specific and saturable whereas that in nonischemic tissue was nonspecific. In vivo binding of nimodipine may be used to identify cell membrane depolarization and calcium channel activation in focal cerebral ischemia.
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PMID:In vivo binding of nimodipine in the brain: II. Binding kinetics in focal cerebral ischemia. 187 9

We prospectively studied the frequency and course of large (greater than 25 cc) and small (less than 25 cc) areas of decreased density in 491 patients with severe closed head injury entered into the Traumatic Coma Data Bank (TCDB). The frequency of such areas and of subarachnoid haemorrhage on initial and subsequent CT scans were recorded. The frequency of large "holes" increased from 8 on the initial CT scan to 24 on scans done from day 4 to day 10. Half of these lesions either completely or almost completely resolved 14 days or more following injury. In patients with small "holes" the frequency increased from 24 to 77, but on scans performed 14 days or more following injury, 47% had completely disappeared. The presence of subarachnoid haemorrhage on the initial scan predicted the development of large areas of decreased density, but it did not predict the development of small areas of decreased density. The disappearance of a substantial number of these areas of decreased density ("holes") indicate that these areas do not necessarily represent areas of cerebral infarction. Patients with closed head injury are at risk for the development of what appear to be regional areas of cerebral ischaemia, but subarachnoid haemorrhage only predicts the development of large areas with these changes. Pharmacologic trials with calcium channel blocking agents or NMDA receptor antagonists in head injured patients appear warranted.
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PMID:Large and small "holes" in the brain: reversible or irreversible changes in head injury. 208 22

We investigated the binding properties of the voltage-sensitive calcium channel antagonist nimodipine in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats weighing 250 g underwent occlusion of both the proximal middle cerebral artery and the ipsilateral common carotid artery. 3H-nimodipine (130 Ci/mmol) was infused intravenously and circulated for 30 minutes before the rats were killed at 5 minutes, 4, 24, and 48 hours after occlusion. The brains were removed and examined by autoradiography. We observed a focal increase of nimodipine binding in severely ischemic regions at 5 minutes after occlusion, which also appeared in regions with presumed penumbral blood flow levels at 4 hours after occlusion. We hypothesize that nimodipine binds to activated calcium channels in ischemic tissue. This increased binding depends on the duration and severity of cerebral ischemia. Sequential measurements of nimodipine binding may allow the identification of regions with potentially reversible effects of ischemia and the monitoring of their response to therapy.
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PMID:Nimodipine binding in focal cerebral ischemia. 217 62

The development of delayed cerebral ischaemia and hence neurological deficit remains a serious problem following subarachnoid haemorrhage. Over recent years, attention has focussed on the use of the dihydropyridine class of calcium channel blocking agents ("calcium antagonists"), in particular nimodipine, as drug therapy in the prophylaxis and treatment of this condition. The theoretical basis for this is briefly discussed and then the clinical experience of the use of calcium antagonists following subarachnoid haemorrhage reviewed. In particular, attention is focussed on the randomised controlled trials that have eventually been able to show that such treatment is beneficial, both in terms of reduction of ischaemic deficit attributable to cerebral "vasospasm" and in clinical outcome, when given prophylactically, although not apparently therapeutically once deficit has developed. The evidence of the mode of action of calcium antagonists in this situation is discussed, again with particular reference to clinical data obtained in situ in the course of such trials. Although the mechanism of action remains unclear, it appears likely that it is at least in part due to the selective cerebral vasodilation induced by these compounds. The necessity for large well-controlled, prospective, randomised clinical trials in the assessment of therapeutic efficacy is stressed.
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PMID:Calcium antagonists in the management of subarachnoid haemorrhage. 222 32

Delayed death of pyramidal neurons of Ammon's horn CA1 sector after short-term forebrain ischemia in Mongolian gerbils represents a type of ischemic neuronal injury in which calcium influx plays an important role. We evaluated the influence of the calcium channel blocker nimodipine in animals subjected to 7.5 minutes of bilateral carotid artery ligation that were given 1 mg/kg i.p. nimodipine at various periods in relation to the ischemic incident. The control animals were subjected to cerebral ischemia with no medication. Five days after ischemia, the state of CA1 sector neurons was morphometrically evaluated and compared with that in animals not subjected to an experimental procedure. Nimodipine exerted a full protective effect on CA1 pyramidal neurons only after repeated application extending over 24 hours after the ischemia. A less conspicuous effect was obtained with a single dose applied at a late postischemic period, and a double dose given in the peri-ischemic stage remained ineffective. The time-dependent effectiveness of nimodipine is discussed in relation to the characteristics of this model of cerebral ischemia.
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PMID:Nimodipine prevents delayed neuronal death of sector CA1 pyramidal cells in short-term forebrain ischemia in Mongolian gerbils. 226 Jan 35


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