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

Experimental and clinical studies have been performed to investigate the validity of a pharmacological approach to prevent delayed ischemic neurologic deficit from vasospasm after subarachnoid hemorrhage: the calcium channel blocker nimodipine was administered intravenously and perivascularly. Pial arteries of cat dilated by 25% during 1 microgram/kg-1 min-1 intravenous infusion; perivascular application of a 2.4 X 10(-5) M solution induced a 21% dilatation, the ethanol-containing solvent alone a 6% dilatation. A 1 microgram/kg-1 min-1 intravenous infusion of nimodipine in patients during EC-IC bypass operation led to a 16% dilatation of pial arteries; the solvent remained without effect. Perivascular application of a 2.4 X 10(-5) M solution during aneurysm surgery evoked a 70-80% dilatation of pial arteries, solvent-treated arteries dilated between 5 and 40%. In a multicenter study on 120 patients with preventive nimodipine treatment and acute operation of ruptured aneurysms, the incidence of delayed cerebral ischemia and fixed neurologic deficit was 1.7%. It is concluded that acute surgery of ruptured cerebral aneurysms and treatment with the calcium antagonist nimodipine substantially reduce the risk of symptomatic vasospasm.
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PMID:Preventive nimodipine and acute aneurysm surgery. Heading for the control of complications after aneurysmal subarachnoid hemorrhage. 389 48

Lidoflazine, a calcium channel blocker, was administered to dogs following twelve minutes of cerebral ischemia, induced by aortic cross-clamping. The effects of lidoflazine (1 mg/kg i.v.) on cerebral blood flow following ischemia was studied in 15 anesthetized, mechanically ventilated dogs. Cerebral blood flow was measured with the radiolabelled microsphere technique before and 10, 30, 60, 90 and 150 minutes following ischemia. Cerebral blood flow increased in all brain regions following ischemia, but by 60 minutes had decreased to control values. Lidoflazine had no effect on this reperfusion phenomenon, or on the distribution of blood flow within the brain. Regional cerebral blood flow was also not altered by lidoflazine therapy. Our data demonstrate that this dose of lidoflazine has no effect on regional or total cerebral blood flow following 12 minutes of cerebral ischemia in dogs. These data do not support perfusion preservation as a mechanism of amelioration of neurologic injury after ischemia by this calcium channel blocker.
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PMID:Effect of lidoflazine on cerebral blood flow following twelve minutes total cerebral ischemia. 642 83

This study was designed to investigate the role of the L-type voltage sensitive calcium channel blocker, isradipine, in the ischemia-induced release of neurotransmitters. Male spontaneously hypertensive rats were subjected to cerebral ischemia for 60 min by bilateral carotid artery occlusion, and recirculated for 120 min. Isradipine (0.25 mg/kg n = 6) or vehicle (n = 6) was administered subcutaneously at 20 min before ischemia. In the striatum, cerebral blood flow was determined by the hydrogen clearance method and concentrations of extracellular dopamine and glutamate were measured by in vivo brain dialysis technique. Extracellular dopamine in the vehicle-treated group increased by 180-fold from the basal level, and glutamate by 24-fold during cerebral ischemia. Isradipine significantly attenuated the ischemic release of dopamine to 33-34% (P < 0.05) of the vehicle group, while it did not affect glutamate release. It is suggested that the release mechanism of dopamine and glutamate during cerebral ischemia may be different, especially in the dependence on the L-type calcium channels.
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PMID:Isradipine, a calcium channel blocker, attenuates the ischemia-induced release of dopamine but not glutamate in rats. 760 97

Focal cerebral ischemia results in increased in vivo binding of calcium channel antagonists to both the L-type voltage sensitive calcium channel (VSCC) and the N-methyl-D-aspartate (NMDA) receptor-linked calcium channel. It was the aim of this study to investigate the effect of focal cerebral ischemia on the in vitro binding of calcium channel antagonists to rat brain. Quantitative autoradiography was used to measure regional in vitro binding of the L-type VSCC antagonist [3H]nimodipine and the competitive NMDA receptor antagonist [3H]CGS-19755 to rat brain following 4 h of irreversible focal cerebral ischemia. [3H]Nimodipine binding to the nonischemic hemisphere was characterized by one binding site with regional binding affinity (KD) estimates ranging from 221 to 482 pM and maximal binding site densities (BMAX) ranging from 13.2 (9.6-17.5) pmol/g tissue (estimate and 95% confidence interval) in CA1 to 32.5 (26.5-39.9) pmol/g tissue in dentate. [3H]CGS-19755 binding to the nonischemic hemisphere was characterized by KD estimates ranging from 59 to 97 nM and BMAX values ranging from 143 (108-192) pmol/g tissue in cortex to 569 (515-641) pmol/g tissue in CA1. For [3H]CGS-19755 a model of two binding sites was applicable in several brain regions. No difference in binding site densities or binding affinities between ischemic and paired nonischemic structures (cortex and striatum) was observed with either ligand. In vitro binding of [3H]nimodipine and [3H]CGS-19755 to ischemic brain failed to identify ischemic-induced changes in calcium channel function previously reported by in vivo binding methods.
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PMID:In vitro binding of [3H]nimodipine and [3H]CGS-19755 to rat brain in focal cerebral ischemia. 767 38

Evidence suggests that ischemic neuronal necrosis may ultimately be the result of excessive intracellular calcium accumulation. In principle, abnormal calcium concentrations during ischemia are derived from three main sources: exaggerated influx via (a) voltage-operated channels, (b) receptor-controlled channels (f. ex. NMDA) and (c) the release of intracellular calcium ion stores. Previous studies using either calcium channel blockers or NMDA antagonists have demonstrated only limited protective effects of these agents in global transient cerebral ischemia, whereas little or no attention has been paid to the calcium sources listed under (c). Dantrolene has been shown to block the increase in free intracellular calcium ion stimulated by either NMDA or glutamate. Thus we postulated that dantrolene might improve neuronal survival in vulnerable regions to ischemia such as the CA1 hippocampus. Male Sprague-Dawley rats (300 approximately 400 g) were prepared for a four-vessel occlusion model of cerebral ischemia. Complete cerebral ischemia was induced by snaring the carotid arteries for 15 mins and maintaining mean arterial pressure at 80 mmHg. Strict attention was paid to keep normal blood gas values. Following ischemia halothane anesthesia was discontinued, and rats were extubated and when stable transferred to cages with free access to water and food. Rats survived for 7 days under close supervision, after which they were anesthetized with pentobarbital and perfused transcardially with 4% paraformaldehyde/sodium-phosphate buffer. The brain was removed and placed in fresh fixatives for another 7 days, after which 40 microns sections were cut and silver-stained.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effects of dantrolene on histological and behavioral outcome in rat CA1 hippocampus after global transient cerebral ischemia]. 769 30

Disturbance of the autoregulation of the cerebral blood flow (CBF) is frequently seen following subarachnoid haemorrhage (SAH) and is possibly partly caused by cerebral ischaemia. It is well-known, that the calcium channel blocker nimodipine reduces the incidence of cerebral infarction and ischaemic dysfunction after SAH. The aim of the present study was to investigate the effect of nimodipine on autoregulation of CBF in an experimental model of SAH. The autoregulation was investigated in 10 control rats with SAH and in 10 nimodipine treated rats with SAH by serial measurements of CBF using a 133Xenon intracarotid injection method during controlled blood pressure manipulations. In the control rats the autoregulation was severely disturbed, no plateau was found where CBF was independent of changes in the arterial blood pressure (MABP). In rats treated with intravenous nimodipine (0.03 mg/kg body weight/h), CBF was 33.0% higher and MABP 5.3% higher compared with the controls. CBF was found constant in the MABP interval between 60 and 100 mmHg which indicates, that nimodipine improves the autoregulation of CBF after SAH.
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PMID:The effect of nimodipine on autoregulation of cerebral blood flow after subarachnoid haemorrhage in rat. 775 67

Although a number of studies have demonstrated the neuroprotective effects of antagonists of postsynaptic N-methyl-D-aspartate (NMDA) and non-NMDA receptors in cerebral ischemia, little is known about the treatment of cerebral infarction through presynaptic blocking of extracellular glutamate release. We evaluated the effects of a presynaptic selective N-type calcium channel antagonist (SNX-111, given intravenously by continuous infusion at 5 mg/kg/h from 20 min prior to occlusion until 2 h postocclusion) on blood flow, extracellular glutamate, and infarct volume in rats with permanent occlusions of the right middle cerebral and right common carotid arteries plus 1-h transient occlusion of the left common carotid artery. There was no significant difference in CBF in the occluded cortex during the experiment between the treated and vehicle groups. SNX-111 significantly reduced total amount of extracellular glutamate during the experiment and the peak value of the glutamate after occlusion from 44.2 +/- 15.8 microM (mean +/- SD) to 21.4 +/- 11.4 microM (p < 0.01). Infusion of SNX-111 also significantly reduced the cortical volume of infarction from 47.2 +/- 5.8 to 19.9 +/- 7.3% (p < 0.0001). These results suggest that SNX-111 has a protective effect against focal ischemia through the inhibition of glutamate release from presynaptic sites, although SNX-111 may also affect the release of other neurotransmitters.
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PMID:A selective N-type calcium channel antagonist reduces extracellular glutamate release and infarct volume in focal cerebral ischemia. 779 Apr 9

The purpose of this study was to evaluate potential mechanisms of ischemia-evoked amino acid transmitter release. Changes in extracellular levels of transmitter amino acids and lactic acid dehydrogenase (LDH) in rat cerebral cortex during and following four-vessel occlusion elicited global cerebral ischemia were examined using a cortical cup technique. Ischemia-evoked release of glutamate, aspartate and gamma-amino-butyric acid (GABA) was compared in control vs. drug-treated animals. Tetrodotoxin and antagonists of glutamate receptors (DNQX, MK-801, and AP-3) depressed the initial rate of increase in extracellular glutamate and aspartate without altering the total amount of these amino acids collected in the cortical superfusates. Cobalt, a calcium channel antagonist, failed to alter efflux. Acidic amino acid transport inhibitors (dihydrokainate, L-trans-PDC) depressed the rate of onset of glutamate and aspartate release and dihydrokainate depressed total release by 44%. PD 81723, an allosteric enhancer at the A1 adenosine receptor, depressed glutamate efflux, as did L-NAME, an inhibitor of nitric oxide synthase. Extracellular increases in GABA levels were depressed by tetrodotoxin and L-trans-PDC. The GABA transport inhibitor, nipecotic acid, increased the initial rate of onset of GABA release. Increases in LDH levels in the extracellular fluid became apparent during the period of ischemia and continued to increase during the subsequent 90 min of reperfusion. These results suggest that ischemia evokes a release of neurotransmitter amino acids that is only partially dependent upon Ca2+ influx activation or the reversal of amino acid transporters. Nonselective mechanisms, resulting from the disruption of plasma membrane integrity, may contribute significantly to the total ischemia-evoked release of excitatory amino acids.
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PMID:Characterization of glutamate, aspartate, and GABA release from ischemic rat cerebral cortex. 791 62

In an in vitro model of cerebral ischemia we investigated the functional consequences of repeated hypoxias and the potential protective effect of the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovaleric acid (D-APV) and the calcium channel blocker verapamil in preventing the expression of pathophysiological activity. Rat neocortical slices were exposed to nitrogen for 2-13 min and the hypoxia-induced functional modifications were monitored in layer II/III by recording the extracellular DC potential, the extracellular calcium concentration ([Ca2+]o) and the stimulus-evoked synaptic responses. Hypoxia caused a reversible 2.4-24.6 mV negative shift in the extracellular DC potential associated with a [Ca2+]o decrease from 1.2 to 0.2 mM and a complete loss of synaptic responsiveness. Repeating hypoxias induced an increase in the amplitude of this anoxic depolarization (AD) and a significant decrease in the AD onset latency. Synaptic responses partially recovered at 20 and 60 min intervals between subsequent hypoxic periods, indicating that the initial AD did not induce any short-term irreparable functional deficits. Verapamil (50 microM) caused an increase in the AD onset latency. However, in comparison to untreated controls, verapamil induced a reduction of excitatory and inhibitory responses during hypoxia probably by blocking voltage-activated calcium conductances. In addition, verapamil did not have any significant effect on the hypoxia-induced reduction of [Ca2+]o. Bath application of D-APV (30 microM) prevented the significant reduction in the AD onset latency to the second hypoxia, but had no significant effect on the AD amplitude and duration. The hypoxia-induced decrease in [Ca2+]o was not altered after addition of D-APV to the bathing medium. These data indicate that the influx of calcium through voltage-activated calcium channels and the NMDA receptor-gated ionophore does not significantly contribute to the massive depolarization observed under hypoxic conditions.
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PMID:Role of NMDA receptors and voltage-activated calcium channels in an in vitro model of cerebral ischemia. 810 Nov 32

Brain retraction is required for adequate exposure during many intracranial procedures. The incidence of contusion or infarction from overzealous brain retraction is probably 10% in cranial base procedures and 5% in intracranial aneurysm procedures. The literature on brain retraction injury is reviewed, with particular attention to the use of intermittent retraction. Intraoperative monitoring techniques--brain electrical activity, cerebral blood flow, and brain retraction pressure--are evaluated. Various intraoperative interventions--anesthetic agents, positioning, cerebrospinal fluid drainage, operative approaches involving bone resection or osteotomy, hyperventilation, induced hypotension, induced hypertension, mannitol, and nimodipine--are assessed with regard to their effects on brain retraction. Because brain retraction injury, like other forms of focal cerebral ischemia, is multifactorial in its origins, a multifaceted approach probably will be most advantageous in minimizing retraction injury. Recommendations for operative management of cases involving significant brain retraction are made. These recommendations optimize the following goals: anesthesia and metabolic depression, improvement in cerebral blood flow and calcium channel blockade, intraoperative monitoring, and operative exposure and retraction efficacy. Through a combination of judicious retraction, appropriate anesthetic and pharmacological management, and aggressive intraoperative monitoring, brain retraction should become a much less common source of morbidity in the future.
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PMID:A review of brain retraction and recommendations for minimizing intraoperative brain injury. 793 45


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