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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effect of chlormethiazole, and other drugs which potentiate gamma-aminobutyric acid (GABA) function on delayed neuronal death in the hippocampus has been examined in the gerbil. 2. Chlormethiazole (100 mg kg-1, i.p.) and two other drugs previously reported to be neuroprotective (dizocilpine, 3 mg kg-1, i.p. and ifenprodil, 4 mg kg-1, i.p.) were all found to prevent neurodegeneration of CA1/CA2 neurones in the hippocampus when given 30 min before a 5 min episode of bilateral carotid artery occlusion. 3. Chlormethiazole (100 mg kg-1) was neuroprotective when given up to 3 h, after the ischaemic episode. 4. Given 1 h after the cartoid artery occlusion, chlormethiazole produced significant protection against hippocampal neurodegeneration at a dose of 50 mg kg-1, but not at 25 mg kg-1. 5. Phenobarbitone (100 mg kg-1, i.p.) and Saffan (alphaxalone, 45 mg kg-1 plus alphadalone, 15 mg kg-1, i.p.) were not protective when given 1 h after the ischaemic episode while pentobarbitone (30 mg kg-1, i.p.) had a modest protective effect. 6. Evidence is presented to show that neither the operating procedure nor the chlormethiazole administration lowered rectal or cerebral temperature. 7. The data suggest that chlormethiazole may be a useful treatment in the prevention of neurodegeneration following stroke or cardiac arrest.
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PMID:Neuroprotective activity of chlormethiazole following transient forebrain ischaemia in the gerbil. 179 7

A combined autoradiographic and immunohistochemical method was used to correlate the extent of focal cerebral ischemia and morphologic ischemic damage following unilateral carotid occlusion in 16 gerbils for 5-30 minutes. Immunohistochemical lesions detectable by the reaction for microtubule-associated proteins 1 and 2 were visible in the subiculum-CA1 and CA2 regions of the hippocampus and layer III/IV of the cerebral cortex after 5 minutes of ischemia (n = 4). Local blood flow was promptly reduced but still heterogeneous after 10 minutes of ischemia (n = 4); local blood flow in immunohistochemical lesions was less than 5 ml/100 g/min except in highly vulnerable regions, where flow values of 5-15 ml/100 g/min were observed. After 15 minutes of ischemia (n = 4) local blood flow in less vulnerable regions including the thalamus and caudoputamen also declined to less than 5 ml/100 g/min, and immunohistochemical lesions became visible in those regions after 30 minutes of ischemia (n = 4). On the other hand, many brain regions tolerated local blood flow of less than 5 ml/100 g/min without ischemic damage. The present study demonstrates that selective tissue vulnerability during progressive cerebral ischemia depends on the degree of hypoperfusion and on factors inherent to neurons in various brain regions.
Stroke 1990 Oct
PMID:Cerebral blood flow and neuronal damage during progressive cerebral ischemia in gerbils. 212 Aug 2

We used brief bilateral carotid artery occlusion in gerbils to examine the effects of temperature on ischemia-induced inhibition of calcium/calmodulin-dependent protein kinase II activity and neuronal death. In normothermic (36 degrees C) gerbils, ischemia induced a severe loss of hippocampal CA1 pyramidal neurons measured 7 days after ischemia (28.4 neurons/mm, n = 10; control density in 10 naive gerbils 262.1 neurons/mm) and a significant decrease in forebrain calcium/calmodulin-dependent protein kinase II autophosphorylation measured 2 hours after ischemia (12.9 fmol/min, n = 6; control phosphorylation in six naive gerbils 23.5 fmol/min). The effect of temperature on these indicators of ischemic damage was examined by adjusting intracerebral temperature before and during the ischemic insult. Hyperthermic (39 degrees C) gerbils showed almost complete loss of neurons in the CA1 region (3.0 neurons/mm, n = 11) and extension of neuronal death into the CA2, CA3, and CA4 regions. In addition, hyperthermia exacerbated ischemia-induced inhibition of calcium/calmodulin-dependent protein kinase II activity (4.2 fmol/min, n = 6). Hypothermia (32 degrees C) protected against ischemia-induced CA1 pyramidal cell damage (257.0 neurons/mm, n = 20) and inhibition of calcium/calmodulin-dependent protein kinase II activity (26.0 fmol/min, n = 6). Our results are consistent with the hypothesis that loss of calcium/calmodulin-dependent protein kinase II activity may be a critical event in the development of ischemia-induced cell death.
Stroke 1990 Dec
PMID:Temperature modulation of ischemic neuronal death and inhibition of calcium/calmodulin-dependent protein kinase II in gerbils. 226 78

Previous studies have shown that pyramidal neurons in hippocampal regions CA1 and CA3 are selectively vulnerable in several neurodegenerative disorders and that a subpopulation of pyramidal neurons in cell cultures of embryonic hippocampus are sensitive to glutamate neurotoxicity. In order to determine whether the patterns of cell loss seen in situ correlate with intrinsic differences in neuronal sensitivities to glutamate-induced degeneration acquired during development, we characterized cultures established from different regions of postnatal rat hippocampus and then examined neuronal sensitivity to glutamate. Tissue corresponding to the dentate gyrus (DG) and regions CA1, CA2 and CA3 of Ammon's horn was removed by microdissection from transverse hippocampal slices and was used to establish cultures of dissociated cells. Cultures from all 4 regions contained 3 major morphological classes of neurons; pyramidal-like, bipolar and stellate. Pyramidal-like neurons comprised the majority of neurons in all cultures; these neurons extended one long and branching axon, and one or more short dendrites. Immunocytochemistry showed that all neurons possessed high levels of glutamate-like and gamma-aminobutyric acid (GABA)-like immunoreactivity when grown in isolation. In contrast, when bipolar and pyramidal neurons were cultured in contact with glial cells, glutamate and GABA immunoreactivity were selectively reduced in the bipolar and pyramidal cells, respectively, suggesting that cell interactions influence neurotransmitter phenotype. Subpopulations of hippocampal neurons from each hippocampal region were vulnerable to glutamate-induced neurotoxicity. Bipolar and stellate cells were resistant to glutamate, while pyramidal-like neurons showed varying degrees of sensitivity to glutamate depending upon which region they were taken from. Experiments with specific glutamate receptor agonists and antagonists demonstrated that both non N-methyl-D-aspartic acid (NMDA) receptors and NMDA receptors mediated glutamate-induced degeneration. There were clear differences in the vulnerability of the pyramidal-like neuron populations in cultures from the different hippocampal regions. The rank order of the vulnerability of pyramidal-like neurons to glutamate-induced neurodegeneration between regions in culture was: DG less than CA2 less than CA3 less than CA1. This pattern of selective vulnerability in cell culture corresponds directly to the pattern of selective cell loss seen in situ in Alzheimer's disease, epilepsy, and stroke suggesting that intrinsic neuronal differences in glutamate sensitivity may be involved in these disorders.
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PMID:Development and selective neurodegeneration in cell cultures from different hippocampal regions. 256 50

Selective degeneration of pyramidal neurons in regions CA1 and CA3 of the hippocampus is a common structural correlate of several neurodegenerative conditions including Alzheimer's disease, epilepsy and stroke. Several lines of evidence suggest that glutamate, an excitatory neurotransmitter intimately involved in learning and memory processes, may also be involved in hippocampal neurodegeneration. High levels of glutamate are toxic to select groups of pyramidal neurons both in vivo and in vitro and subtoxic levels of glutamate can cause the regression of pyramidal neuron dendrites. In order to determine the basis for this selective vulnerability we employed two rat hippocampal culture paradigms. The first paradigm consisted of neurons isolated from different hippocampal regions (CA1, CA2, CA3, dentate gyrus). Selective vulnerability in the isolated neurons mirrored the selective cell loss that occurs in situ. Dentate granule cells and CA2 pyramidal-like neurons were relatively resistant to glutamate-induced neurodegeneration, while CA1 and CA3 pyramidal neurons were significantly more vulnerable. The second paradigm consisted of sister pyramidal neurons arising from a common progenitor cell. Sister neurons were found to be either both sensitive or both resistant to the degenerative effects of glutamate indicating that mitotic history was an important determinant of selective vulnerability. Experiments which examined the cellular mechanisms underlying selective vulnerability revealed that glutamate caused a large and sustained rise in intracellular calcium levels only in vulnerable neurons. Pharmacological experiments with glutamate receptor antagonists, the inhibitory transmitter GABA, and calcium blockers indicated that vulnerable, but not resistant, neurons expressed glutamate receptors which mediated large rises in intracellular calcium and subsequent degeneration. These results indicate that intrinsic differences in the expression of glutamate receptors linked to calcium influx may account for selective neuronal vulnerability. Treatments which block glutamate receptors, suppress electrical activity, or block calcium channels directly may prove useful in preventing the degeneration of the hippocampal circuitry whose integrity is critical for learning and memory processes.
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PMID:Intrinsic factors in the selective vulnerability of hippocampal pyramidal neurons. 269 Jan 6

To investigate experimentally the mnemonic and neuropathological effects of blockage of the posterior cerebral arteries (PCA), a cerebrovascular accident that can lead to global anterograde amnesia in humans, we permanently occluded these arteries bilaterally in six monkeys and then evaluated their performance on a visual recognition task, after which we assessed the extent of their ischemic infarcts. The latter showed substantial individual variation, ranging from almost no damage in one case to massive unilateral injury of both the ventromedial o occipitotemporal cortex and hippocampal formation in another. In the four remaining cases, however, the infarcts fell within a narrow range, being confined almost entirely to the hippocampal formation and parahippocampal gyrus, and then only to restricted portions of these structures, unilaterally in one case, and bilaterally in the three others. Performance on the recognition task was related to the presence and bilaterality of the hippocampal injury. Thus, the case without any hippocampal damage performed at a rate equal to that of normal controls; the case with unilateral hippocampal damage was mildly impaired; and the three cases with bilateral infarctions, involving between 20 and 55% of the hippocampal formation, showed substantial impairment, with scores averaging 20% below those of normal controls. The only subfields of the hippocampus damaged in common in these cases were CA1 and CA2. Paradoxically, the memory loss found in these three animals with only partial bilateral hippocampal damage was significantly greater than that found in animals with total bilateral ablation of the hippocampal formation, whose scores averaged only 10% below those of normal controls. Possible explanations for this extremely puzzling outcome are proposed.
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PMID:Mnemonic and neuropathological effects of occluding the posterior cerebral artery in Macaca mulatta. 271 Mar 18

We examined the effect of lidocaine on ischemic neuronal injury in the rat forebrain ischemia model. Cerebral ischemia was achieved with bilateral carotid artery occlusion and controlled hypotension to a mean of 50 torr for 10 minutes. Perfusion-fixation was performed 7 days after ischemia, subsequent to which the brains were sectioned coronally and stained with hematoxylin and eosin. Ischemic neuronal injury was quantitatively expressed (after direct counting) as a percentage of total neurons, that is, ischemic neurons divided by (ischemic neurons + normal neurons). Predictably, the selectively vulnerable hippocampal areas exhibited the most marked neuronal injury. In the CA1/CA2 sectors, lidocaine-treated rats demonstrated less injury (34 +/- 14%) than untreated (64 +/- 9%) or saline-treated (70 +/- 10%) rats. However, these superficially pronounced numerical differences were not of statistical significance (p greater than 0.05). In the CA3 sector, neuronal injury in lidocaine-treated rats (31 +/- 14%) was significantly different at p less than 0.05 from the untreated (80 +/- 5%) but not the saline-treated (59 +/- 13%) group. We conclude that lidocaine may have an only marginal beneficial effect on forebrain ischemia in rats.
Stroke 1989 Jan
PMID:Effect of lidocaine on forebrain ischemia in rats. 291 25

The effects of mannitol, nimodipine, and indomethacin on ischemic neuronal injury were examined in 45 rats divided equally into nine groups subjected to 10 minutes of forebrain ischemia. Of two control groups, one received maintenance fluids while the other received a normal saline bolus. In the remaining seven groups, mannitol, nimodipine, and indomethacin were administered singly or in combination 5 minutes before forebrain ischemia. Seven days after ischemia, the brains were perfusion-fixed, sectioned coronally into 2.8-mm slices, and stained with hematoxylin and eosin. Ischemic neurons were directly counted on predetermined regions of standardized serial sections. Considerable amelioration of ischemic injury (ischemic neurons/total neurons) was observed with mannitol (ischemic injury, 7 +/- 5% in the hippocampal CA1/CA2 sectors and 28 +/- 17% in the CA3 sector). This is in contrast to control values of 64 +/- 11% and 80 +/- 6%, respectively, and those obtained in the normal saline group of 70 +/- 10% and 59 +/- 13%, respectively. The beneficial effect with nimodipine reached significance in only the hippocampal CA3 sector (ischemic injury, 35 +/- 21%). Indomethacin showed no significant benefit. Combining the agents resulted in significantly reduced neuronal injury compared with control groups, although the effect was not greater than that achieved with mannitol alone. The degree of ischemic injury was least when all three agents were used in combination (ischemic injury, 12 +/- 12% in the hippocampal CA1/CA2 sectors and 4 +/- 4% in the CA3 sector). Our data support the concept that successfully blocking the ischemic cascade with a single, diversely acting agent or multiple agents will evoke the best beneficial response.
Stroke 1988 May
PMID:Effect of mannitol, nimodipine, and indomethacin singly or in combination on cerebral ischemia in rats. 312 27

We investigated progression and recovery of neuronal damage during and after global cerebral ischemia in gerbils after bilateral occlusion of the common carotid arteries, using the immunohistochemical method (reaction for tubulin and creatine kinase BB-isoenzyme). The earliest, but reversible, ischemic lesions occurred after 3 minutes' ischemia in the subiculum-CA1 and CA2 regions of the hippocampus. The lesions became irreversible after 4 minutes' ischemia. The ischemic and postischemic lesions in the cerebral cortex, thalamus, and caudoputamen were partially or completely reversible if the ischemic period was 5 minutes, whereas delayed degeneration occurred in the pyramidal cells of the medial CA1 region after reperfusion for 48 hours (delayed neuronal death). After 10 minutes' ischemia and subsequent reperfusion, delayed neuronal death extended from the medial to the lateral CA1 region; the ischemic and postischemic lesions in the cerebral cortex, thalamus, and caudoputamen also expanded during reperfusion. Our investigation demonstrates that selective vulnerability existed in global cerebral ischemia as in incomplete or regional ischemia and suggests that neurons in many areas of the brain possessed the potential for recovery, progressive deterioration, and even delayed neuronal death depending on the severity and duration of cerebral ischemia.
Stroke 1988 Dec
PMID:Immunohistochemical investigation of ischemic and postischemic damage after bilateral carotid occlusion in gerbils. 320 12

The effect of selective injury of hippocampal neurons on the consolidation of memory traces was studied in gerbils (meriones unguiculatus) after production of mild cerebral ischemia. The right carotid artery was permanently ligated, and animals without gross neurological deficits ("symptom-negative" gerbils) were selected. Eight days and eight weeks after vascular ligation, cell counts of hippocampal neurons were carried out and correlated with regional blood flow and the acquisition of operant behaviour. Eight days after carotid artery occlusion, learning behaviour was significantly impaired although the number of hippocampal neurons had not changed and blood flow had even increased above normal. After eight weeks, learning behaviour and blood flow were normal but now a significant loss of pyramidal neurons was present in the CA1 and CA2 sectors of the hippocampus. Our observations demonstrate that it is possible to detect subtle functional disturbances by appropriate behavioural investigation before manifestation of selective injury of the hippocampus. Recovery of integrative function, despite persistent cellular damage, provides further evidence for central nervous plasticity.
Stroke
PMID:Selective vulnerability of hippocampus and disturbances of memory storage after mild unilateral ischemia of gerbil brain. 381 Jul 15


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