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

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

The protective effect of E-2001 (2-(4-(p-fluorobenzoyl)-piperidin-1-yl)-2'-acetonaphthone hydrochloride) was examined in various ischemic models, and the mechanisms of its action were investigated in vitro and in vivo. 1. Pretreatment with E-2001 ameliorated the degeneration of pyramidal neurons in the hippocampal CA1 sector following transient ischemia in Mongolian gerbils. 2. E-2001 improved stroke symptoms induced by permanent unilateral carotid artery ligation in gerbils. 3. E-2001 prolonged the survival time following permanent bilateral carotid artery ligation in gerbils and mice. E-2001 also prolonged the survival time following intravenous injection of KCN into mice. 4. E-2001 suppressed the high potassium-evoked release of glutamate from rat hippocampal slices. Furthermore, E-2001 prevented the excessive accumulation of extracellular glutamate induced by a brief ischemia in gerbils. 5. E-2001 exerted calcium antagonistic action, i.e., a relaxing effect on high potassium-induced contraction of rat aorta. 6. E-2001 exerted inhibitory action on the lipoperoxide production in vitro and in vivo, and exhibited a radical scavenging effect against O- and N-radicals. These results suggest that E-2001 might be effective as a novel anti-ischemic agent.
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PMID:Anti-ischemic effect of the novel anti-ischemic agent 2-(4-(p-fluorobenzoyl)-piperidin-1-yl)-2'-acetonaphthone hydrochloride and possible mechanism of its action. 275 30

We looked at FiO2, choice of anesthetic, nutritional status, and body temperature in a gerbil model of forebrain ischemia to determine their effect on data interpretation, ischemic outcome, and extent of pharmacologic protection. We subjected 484 gerbils to 5 minutes of forebrain ischemia under different experimental conditions. The gerbils were anesthetized with 3% halothane and inspired 21% O2, 37% O2 and 60% N2O, or 97% O2. Six groups of gerbils pretreated with 200 mg/kg phenytoin or 2 ml/kg polyethylene glycol (vehicle) underwent ischemia in the fasted or fed state. Three groups of gerbils receiving no pretreatment underwent ischemia with rectal temperatures of 32-33 degrees C, 34-35 degrees C, or 37 degrees C. We counted intact neurons in the CA1 hippocampal sector in brains fixed on Day 7 after ischemia. t tests of square-root-transformed cell counts were used to assess the effect of hypothermia, and analysis of variance of the transformed data was used to test for the effects of phenytoin, FiO2, and nutritional status. Phenytoin pretreatment provided significant protection from CA1 neuron loss in all groups tested (p less than 0.001), but the degree of protection varied from 20% to 44%. In spite of significantly higher serum glucose concentrations in fed than in fasted gerbils (173 and 118 mg/dl, respectively), we found no significant effect of nutritional status upon neuron loss in phenytoin- or vehicle-pretreated gerbils. An FiO2 of 21% significantly decreased the number of viable neurons in both vehicle- and phenytoin-pretreated groups (p less than 0.03), despite the lack of an effect of hypoxemia on arterial blood gases.(ABSTRACT TRUNCATED AT 250 WORDS)
Stroke 1989 Nov
PMID:Conditions for pharmacologic evaluation in the gerbil model of forebrain ischemia. 281 90

The ability of the kappa-opioid receptor agonists U50488H and U62066E (spiradoline mesylate) compared with the non-kappa close structural analogue U54494A to affect postischemic necrosis of the selectively vulnerable hippocampal CA1 neurons was examined in male Mongolian gerbils. The gerbils were treated with either saline vehicle or 10 mg/kg i.p. of one of the test drugs 30 minutes before and again 2 hours after a 10-minute period of bilateral carotid artery occlusion or sham occlusion under light methoxyflurane anesthesia. Seven days after ischemia and reperfusion the brains were perfusion-fixed, and hippocampal CA1 cells were counted in a blind fashion. In ischemic gerbils that received only vehicle, there was a 78.9% loss of CA1 neurons compared with sham-occluded gerbils. In contrast, in U50488H-treated gerbils, mean cell loss was reduced to 33.9% (p less than 0.01 vs. vehicle-treated group). U62066E was even more effective in reducing postischemic CA1 degeneration to only 20.7% (p less than 0.0001 vs. vehicle-treated group). However, treatment with the non-kappa analogue U54494A did not cause any apparent protection; the gerbils in this group showed an 80.7% loss of CA1 neurons. Our results are consistent with the hypothesis that kappa-receptor stimulation is associated with improved postischemic neuronal preservation.
Stroke 1988 Aug
PMID:Quantitative analysis of effects of kappa-opioid agonists on postischemic hippocampal CA1 neuronal necrosis in gerbils. 284 Jul 59

Peptides derived from each of the 3 endogenous opioid precursors were measured in gerbil brain regions at various times after transient bilateral carotid artery occlusion using radioimmunoassays specific for beta-endorphin-, met-enkephalin-, and dynorphin A-related peptides. Lasting changes were observed only in the hippocampus. The most striking effect was on dynorphin A immunoreactivity, which was reduced by 30-40% as early as 1 hour after recirculation and remained at 50% of the control level for at least 1 week. In some experiments dynorphin levels showed a transient recovery at 24 hours. These results demonstrate a unique sensitivity of the dynorphin-containing dentate granule cell-mossy fiber pathway to transient ischemia. Although these cells remain histologically intact, the decrease in dynorphin level precedes and continues during the delayed loss of hippocampal CA1 neurons characteristic of this model and further defines the selective vulnerability of hippocampal circuitry following ischemia. These observations clearly identify the hippocampus as a well-defined brain region in which further studies of the postischemic pathophysiology of endogenous opioid peptides may provide a rational basis for evaluating the place of opiate pharmacology in stroke treatment.
Stroke
PMID:Opioid peptide levels in gerbil brain after transient ischemia: lasting depletion of hippocampal dynorphin. 288 47

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

We investigated the effects of intravenous application of nimodipine on the neurophysiologic, biochemical, and morphologic consequences of 15 minutes of global cerebral ischemia in seven rabbits. In vivo dialysis of the hippocampus was used to determine changes in extracellular concentrations of extracellular calcium and amino acids and blood-brain barrier permeability. Ischemia without treatment produced a rapid disappearance of electroencephalographic activity, a decrease in the concentration of extracellular calcium, the release of neuroactive amino acids, and leakage of methionine to the tissue fluid, plus a significant increase of the blood-brain barrier permeability to fluorescein. Except for permeability and electroencephalographic activity, these parameters normalized during 45 minutes of recirculation; permeability and activity failed to normalize completely during 3 hours of recirculation. After 3 hours of recirculation, morphologic changes in the CA1 hippocampal area were observed. Treatment with nimodipine significantly enhanced electroencephalographic activity recovery and normalization during recirculation, reduced the decrease in extracellular calcium concentration, and prevented the increased permeability of the blood-brain barrier. Nimodipine protected the CA1 area from early morphologic changes and reduced leakage of methionine from brain cells. The beneficial cytoprotective effect of nimodipine, probably related to normalization of calcium homeostasis and blood-brain barrier permeability after ischemia, may reflect both vascular and cellular sites of action.
Stroke 1989 Jan
PMID:Beneficial effect of nimodipine on metabolic and functional disturbances in rabbit hippocampus following complete cerebral ischemia. 291 38

We tested the efficacy of various putative neuroprotective agents in the gerbil model of delayed neuronal death. The selective loss of anterior CA1 neurons of the hippocampus 4 days after 5 minutes of bilateral ischemia was complete in greater than 90% of the gerbils examined. We tested 11 agents for their ability to protect against neuronal loss. Only those agents that were associated with the GABAergic system exhibited protection and only when administered before the ischemic insult. The possibility that delayed neuronal death is the result of a primary defect in inhibitory neurotransmission is considered.
Stroke 1989 Feb
PMID:Role for gamma-aminobutyric acid in selective vulnerability in gerbils. 291 17

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


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