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)

We report the regional variation in relative in vivo binding of the L-type voltage sensitive calcium channel (VSCC) antagonist [3H]nimodipine to brain following transient forebrain ischemia in the rat. At 30-min of reperfusion after 20 min of forebrain ischemia, [3H]nimodipine binding was significantly increased in striatum, CA3 and CA4, and dentate relative to binding in sham-operated rats, suggesting that VSCCs were responding to ischemic depolarization. Two h following ischemia, binding in all brain structures returned to normal levels indicating repolarization of cell membranes. At 24 h of recirculation, increased [3H]nimodipine binding was again observed in striatum and dentate. Binding remained elevated in the striatum and dentate, and increased binding became evident in the CA1 region of the hippocampus after 48 h of reperfusion. With the exception of the dentate gyrus, the second rise in [3H]nimodipine binding anticipated or coincided with the observed regional ischemic cell changes. These observations in global cerebral ischemia support previous work indicating that in vivo binding of [3H]nimodipine to the L-type VSCC may be an early and sensitive indicator of impending ischemic injury. Such measurements may be of use in identifying vulnerable brain regions and defining a therapeutic window of opportunity in models of cerebral ischemia.
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PMID:In vivo binding of [3H]nimodipine in rat brain after transient forebrain ischemia. 816 82

We investigated the relationships among N-methyl-D-aspartate, glycine, L-type voltage-dependent calcium channels, and [3H]dopamine release in a canine model of global cerebral ischemia/reperfusion. The binding of [3H]PN200-110 ([3H]isradipine) to L-type voltage-dependent calcium channels, that open as a consequence of N-methyl-D-aspartate-induced changes in membrane potential, was approximately doubled in striatal membranes prepared from ischemic animals relative to controls, and remained significantly elevated at 30 min and 2 h of reperfusion. These changes coincided temporally with changes in the ability of the voltage-sensitive calcium channel blocker nitrendipine to inhibit glycine enhancement of N-methyl-D-aspartate-stimulated [3H]dopamine release in striatal slices prepared from the same animals. Compared with nonischemic controls, N-methyl-D-aspartate-stimulated [3H]dopamine release was increased in ischemic animals and remained increased throughout reperfusion up to at least 24 h. Glycine enhanced N-methyl-D-aspartate-stimulated release in all treatment groups. The enhancement of N-methyl-D-aspartate-stimulated dopamine release by glycine was reduced by the inclusion of nitrendipine in striatal slices from ischemic and 30-min reperfused animals. These data suggest that glycine may facilitate opening of the voltage-dependent calcium channels activated by N-methyl-D-aspartate and that this facilitation is blocked by the antagonist nitrendipine.
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PMID:Increased activation of L-type voltage-dependent calcium channels is associated with glycine enhancement of N-methyl-D-aspartate-stimulated dopamine release in global cerebral ischemia/reperfusion. 820 31

1. Putrescine has been implicated in modulating cytoplasmic calcium concentration and is correlated with selective neuronal vulnerability in cerebral ischaemia. In order to determine whether putrescine modulates voltage-activated calcium channels, whole-cell and single channel patch clamp experiments were performed with N1E-115 mouse neuroblastoma cells. 2. L-type calcium channel currents showed a 34 +/- 21% increase (n = 6 cells) during external application of 1 mM putrescine. There was no change in the kinetics of the current and no shift in the current-voltage relationship along the voltage axis. 3. T-type calcium channel currents were not affected by 1 mM putrescine. 4. The effect of putrescine on single L-type calcium channels was studied using the cell-attached configuration of the patch clamp technique. Putrescine (5 mM) applied to the bathing solution, but not present in the pipette, caused an increase in open time of the single channel current without changing the conductance of the channel. In 345 depolarizing steps compiled from three cells, the number of channel openings longer than 3 ms increased from six to seventy-six, and the number of channel openings longer than 9 ms increased from zero to twenty-seven. This single channel study supports the hypothesis that putrescine acts on the L-type channel from the inside of the cell. 5. External application of 1 mM spermine and 1 mM spermidine had no effect on T- and L-type calcium channels. Thus, the effect of putrescine is probably not mediated by the higher polyamines. 6. In order to test whether the effect of putrescine is mediated by a second messenger, specific protein kinase C and cyclic AMP-dependent protein kinase inhibitors, staurosporine and KT5720, respectively, were applied prior to putrescine. When cells were preconditioned with 200 nM staurosporine, the increase of the L-type calcium current by 1 mM putrescine was inhibited. By contrast, 200 nM KT5720 did not inhibit the putrescine effect. Therefore, the increase of L-type channel currents by putrescine may be mediated by protein kinase C but not the cyclic AMP-dependent protein kinase. 7. The putrescine-induced enhancement of the L-type calcium channel activity may play an important role in calcium-induced neurotoxicity.
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PMID:The effect of polyamines on voltage-activated calcium channels in mouse neuroblastoma cells. 839 76

A 3-year-old Chinese girl with alternating hemiplegia syndrome failed to respond to anticonvulsants, antimigrainous drugs, and calcium channel blockers. She made a complete remission with a 4-week course of steroid, and relapsed after steroid withdrawal. Electroencephalogram and brain mapping during the hemiplegic attack showed unilateral high-voltage sharp slow-wave discharges in the temporo-occipital region contralateral to the hemiplegic side and diffuse high-voltage slowing during attacks of quadriplegia or other clinical manifestation such as dullness, lethargy, or yawning. Brain perfusion single photon emission computed tomographic (SPECT) scan study during the attack showed decreased uptake in the temporoparietal region contralateral to the hemiplegic side and in the ipsilateral basal ganglia, whereas the perfusion was normal between attacks. Electroencephalogram background activity was improved while the child was in clinical remission with steroid treatment. Computed tomographic and magnetic resonance imaging scans of the brain were normal. Carotid angiogram failed to show any structural or dynamic changes of the carotid arteries. The possible mechanism underlying alternating hemiplegia syndrome might be transient and reversible cerebral ischemia with high-voltage slow-wave discharges shown in the electroencephalogram and decreased perfusion in SPECT scan.
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PMID:Alternating hemiplegia syndrome: electroencephalogram, brain mapping, and brain perfusion SPECT scan study in a Chinese girl. 840 62

The anti-ischemic and anoxic effects of NC-1100, a piperazine type calcium channel blocker, were investigated in various cerebral ischemia and anoxia models in mice, gerbils and guinea pigs. Minimal effective doses of NC-1100 were 8 mg/kg, i.p. and 30 mg/kg, p.o. for KCN-induced anoxia; 16 mg/kg, i.p. for decapitation-induced gasping; 30 mg/kg, i.p. for cerebral ischemia induced by occlusion of bilateral carotid arteries in gerbils; and 10 microM for the in vitro ischemic model in hippocampal slices. Moreover, NC-1100 attenuated the disturbance of cerebral energy metabolism induced by decapitation in mice. These results suggest that NC-1100 has a cerebral protective effect, and that attributable to its ability to improve the cerebral energy metabolism disturbance.
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PMID:[Effects of NC-1100, a calcium channel blocker, on experimental cerebral ischemia/anoxia in rodents]. 848 22

Neurologic injury that occurs after ischemia results from a cascade of events involving the release of various endogenous neurotoxins. A portion of the release of excitatory neurotransmitters is calcium dependent and may be attenuated by administration of calcium channel blockers. Using an in vivo model of ischemia, we studied the effects of omega-conopeptide MVIIC, a voltage-sensitive calcium channel blocker, and hypothermia (32 degrees C) on hippocampal glutamate and aspartate release in the peri-ischemic period. Thirty-four New Zealand white rabbits of either sex were anesthetized with halothane, intubated, and mechanically ventilated. Monitored variables included blood gases, mean arterial blood pressure, and the electroencephalogram. Microdialysis catheters were transversely inserted through the anterior portion of the dorsal hippocampus and perfused with artificial cerebrospinal fluid at a rate of 2 microliters/min. After stabilization period, animals were randomly assigned to one of the following groups: Control group (n = 8), 10 microM omega-conopeptide MVIIC group (n = 7), 100 microM omega-conopeptide MVIIC group (n = 7), Hypothermia group (n = 6; cranial temperature = 32 degrees C), and omega-conopeptide MVIIC + hypothermia group (n = 6; 100 microM omega-conopeptide MVIIC and cranial temperature 32 degrees C). All the rabbits were subjected to 10 minutes of global cerebral ischemia produced by neck tourniquet inflation combined with hypotension during halothane anesthesia. Conopeptide MVIIC was administered in the artificial cerebrospinal fluid used to perfuse the microdialysis catheter. In control animals, ischemia caused a significant increase in glutamate (9.7 fold) and aspartate (11.3 fold) concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transient brain ischemia in rabbits: the effect of omega-conopeptide MVIIC on hippocampal excitatory amino acids. 854 94

Levemopamil, a novel calcium channel blocker with antagonistic action on serotonin S2-receptors has been reported to be a promising compound for therapy in cerebral ischemia. This data has been obtained in the rat only, and it is of interest to determine if these beneficial effects are present in other models of ischemia in other species. The present study was therefore designed to examine its effect on histological outcome and changes in EEG after focal cerebral ischemia and reperfusion in the cat. Focal cerebral ischemia was induced by a reversible 1 hour occlusion of the middle cerebral artery followed by reperfusion of the brain. Six hours after the induction of the insult, the brain was perfusion-fixed and evaluated for histological damage by light microscopy. In 8 animals an intravenous infusion of levemopamil was initiated 5 minutes after middle cerebral artery occlusion at a rate of 4 mg/kg/h for 15 min and then at 0.6 mg/kg/h until the end of the study. A control group (n = 7) received a similar infusion of saline. The EEG amplitude did not differ between the two groups at any point of the study. The area of ischemic damage in the sections obtained for histological examination at 1-mm intervals, as well as the total volume of ischemic damage for both groups (treated: 1.33 cm3; untreated: 0.97 cm3) also did not show any significant differences. These results indicate that postischemic treatment with levemopamil at this dose, and in this model of focal cerebral ischemia and reperfusion, does not attenuate the ischemic damage.
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PMID:Failure of levemopamil to improve histological outcome following temporary occlusion of the middle cerebral artery in cats. 858 75

It have been reviewed the different mechanisms involved in the development of cerebral ischemia and infarct, as well as the possible interaction and potentiation among them. Experimental and clinical trials undertaken with different drugs, such as glutamate antagonists, calcium channel blockers and free radical antagonists are discussed on the light of their possible application in prophylactic neuroprotection.
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PMID:[Neuroprotection in cerebral ischemia]. 871 48

1. The neuroprotective properties of fasudil (HA1077), a novel protein kinase inhibitor, were evaluated in two animal models of cerebral ischaemia: transient bilateral carotid artery occlusion in Mongolian gerbils and cerebral microembolization in rats. 2. The cytoprotective effect of fasudil on delayed neuronal death in gerbils was compared with the effects of nimodipine, a calcium channel antagonist and ozagrel, a thromboxane A2 synthetase inhibitor. The average of the neuronal cell density in the ischaemic control group was 17.8 +/- 2.1 cells mm-1, whereas fasudil (30 mg kg-1) significantly diminished the loss of CA1 neurones with the average of the neuronal cell density of 101.0 +/- 22.0 cells mm-1; nimodipine (10 mg kg-1) and ozagrel (30 mg kg-1) did not significantly protect against the ischaemia-induced neuronal loss. 3. In the rat model, the effects of fasudil on the histological and neurological consequences of cerebral microembolization produced via the injection of microspheres were examined. Twenty-four hours after the injection of microspheres into the internal carotid artery, all animals in the control group showed typical symptoms of stroke. Neurological function was significantly improved in the fasudil-treated animals. In the controls, the infarcted area in a cortical slice selected to include the hippocampal area was 0.25 +/- 0.01 cm2 (mean +/- s.e.mean) (43.9 +/- 2.4% of cortical section of the half hemisphere); the difference was significant compared to the mean area of 32.7 +/- 2.8 and 21.5 +/- 4.8% observed in rats treated with fasudil (3, 10 mg kg-1), respectively. Fasudil (10 mg kg-1) significantly suppressed the increased water content in ischaemic brain tissues (saline-treated rats, 82.4 +/- 0.2% vs fasudil-treated rats, 81.0 +/- 0.4%). 4. These results suggest that: (i) various protein kinases are involved in the pathogenesis of ischaemic injury; and (ii) the inhibition of protein kinases may be efficacious in preventing neuronal death, thus improving neurological function in the brain damage associated with ischaemic stroke.
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PMID:Neuroprotective properties of a protein kinase inhibitor against ischaemia-induced neuronal damage in rats and gerbils. 884 19

Resting and depolarization-induced 45CaCl2 accumulation was compared for synaptosomes isolated from hibernating and nonhibernating ground squirrels. Channel subtype antagonists were used to identify the active voltage-sensitive calcium channel subtypes in these preparations. There was significantly less 45Ca2+ accumulation in synaptosomes isolated from hibernating as compared to cold-adapted nonhibernating ground squirrels in both basal (p < 0.005) and depolarizing (p < 0.03) media over a 30 sec to 5 min incubation period. The elevation in 45Ca2+ accumulation triggered by K+ depolarization was blocked by 50 microM CdCl2, 1 microM omega-conotoxin MVIIC or 1 microM omega-agatoxin IVA. Inhibition was not observed with 1 microM nifedipine or with 1 microM omega-conotoxin GVIA. These results suggest that hibernation is associated with reduced presynaptic 45Ca2+ conductance via voltage-sensitive channels with a pharmacological sensitivity that is different from the established L-, N-, and P-types in other systems but share features of the recently described Q-type calcium channel. This decrease may reflect a cellular adaptation that helps confer tolerance to the near total cerebral ischemia associated with hibernation.
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PMID:Decreased calcium accumulation in isolated nerve endings during hibernation in ground squirrels. 889 49


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