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)

1. We investigated the alterations in binding sites of three major second messengers, phorbol 12,13-dibutyrate, inositol 1,4,5-trisphosphate and forskolin following transient cerebral ischemia in gerbils, and examined the effects of a novel vinca alkaloid derivative, vinconate against the alterations in the binding of the second messengers following ischemia. 2. Transient cerebral ischemia produced by bilateral occlusion of the common carotid arteries was induced for 10 min, and intraperitoneal administration of vinconate (100 mg/kg and 300 mg/kg) was given 10 min before ischemia. 3. Morphological study indicated that transient ischemia can produce severe neuronal damage in striatum, hippocampal CA1 sector and hippocampal CA3 sector. 4. Transient cerebral ischemia caused the postischemic alterations in the binding of three second messengers. 5. The postischemic alterations in the binding of second messengers were ameliorated by pretreatment with vinconate. This effect was especially observed in the striatum which was most vulnerable to ischemia. 6. These findings are discussed in relation to the mechanism of ischemic neuronal damage.
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PMID:Protective effect of a novel vinca alkaloid derivative, vinconate, against alterations in binding sites of second messengers after transient cerebral ischemia in gerbils. 159 19

We studied delayed postischemic calcium accumulation and neuronal damage in the gerbil brain, using 45Ca autoradiography as a marker for detection of injured tissue and light microscopy. Transient cerebral ischemia was induced for 15 min. Sham-operated gerbils showed no abnormal calcium accumulation and neuronal damage throughout the brain. At 2 and 7 days following 15 min of ischemia, marked calcium accumulation and mild to severe neuronal damage were found in the selectively vulnerable areas such as neocortex, striatum, hippocampus and thalamus, and brainstem such as medial geniculate body, substantia nigra and inferior colliculus. After 1-2 months of recirculation, the calcium accumulation was not recognized in the brainstem. But, the accumulation was still detectable in the striatum, the hippocampus and the thalamus. Morphological study showed that marked proliferation of glia cells was rapid in the inferior colliculus and was relatively slow in the striatum and the hippocampus, although these structures were severely damaged after ischemia. The result suggests that the speed of restoration of injured tissue and the mechanisms for the damage after cerebral ischemia may be different between the selectively vulnerable areas and the brainstem. Furthermore, they suggest that 45Ca autoradiographic technique may provide a useful approach for diagnosis of the restoration of injured tissue at chronic stage following cerebral ischemia.
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PMID:Long-term observations on calcium accumulation in postischemic gerbil brain. 204 98

Transient cerebral ischemia in normoglycemic animals is followed by a decrease in glucose utilization, reflecting a postischemic cerebral metabolic depression and a reduction in the activity of the pyruvate dehydrogenase complex (PDHC). Preischemic hyperglycemia, which aggravates ischemic brain damage and invariably causes seizure, is known to further reduce cerebral metabolic rate. To investigate whether these effects are accompanied by changes in PDHC activity, the postischemic cerebral cortical activity of this enzyme was investigated in rats with preischemic hyperglycemia (plasma glucose 20-25 mM). The results were compared with those obtained in normoglycemic animals (plasma glucose 5-10 mM). The activated portion of PDHC and total PDHC activity were measured in neocortical samples as the rate of decarboxylation of [14C]pyruvate in crude brain mitochondrial homogenates after 5 min, 15 min, 1 h, 6 h, and 18 h of recirculation following 15 min of incomplete cerebral ischemia. In normoglycemic animals the fraction of activated PDHC, which rises abruptly during ischemia, was reduced to 19-25% during recirculation compared with 30% in sham-operated controls. In hyperglycemic rats the fraction of activated PDHC was higher during the first 15 min of recirculation. However, after 1 and 6 h of recirculation, the fraction was reduced to values similar to those measured in normoglycemic animals. Fifteen of 26 rats experienced early (1-4 h post ischemia) seizures in the recovery period. The PDHC activity appeared unchanged prior to these early postischemic seizures. We conclude that the accentuated depression of postischemic metabolic rate observed in hyperglycemic animals is not coupled to a corresponding postischemic depression of PDHC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preischemic hyperglycemia and postischemic alteration of rat brain pyruvate dehydrogenase activity. 234 83

Vasoactive arachidonic acid metabolites are postulated to play a role in the pathogenesis of cerebral ischemia. In order to characterize the local generation of cyclooxygenase and lipoxygenase metabolites of arachidonic acid in transient ischemia with reperfusion, Mongolian gerbils were studied for regional cerebral blood flow (CBF), using the hydrogen clearance technique, and for cerebral levels of the thromboxane metabolite TXB2, and prostaglandins 6-keto-PGF1 alpha and PGE2, as well as the leukotriene LTB4. The gerbils were anesthetized with pentobarbital, and half of the animals were pretreated with the cyclooxygenase inhibitor indomethacin. All received 10 or 20 minutes of dense forebrain ischemia followed by reperfusion of 10 minutes, 50 minutes, or 100 minutes. A separate control group received no ischemic lesion. Regional CBF decreased significantly from 23.7 +/- 2.6 to 4.3 +/- 1.7 cc/100 gm/min during ischemia (p less than 0.01). Reperfusion resulted in initially normal flows (22.5 +/- 5.1 cc/100 gm/min) followed by a progressive hypoperfusion (11.3 +/- 2.7 cc/100 gm/min). All metabolites showed parallel significant (p less than 0.05) increases after transient ischemia and reperfusion compared to baseline levels (values (in pg/mg protein) were: TXB2 45.5 +/- 7.1 vs 23.3 +/- 3.6; 6-keto-PGF1 alpha 262.8 +/- 47.9 vs 175.8 +/- 26.8; PGE2 256.5 +/- 35.6 vs 112.5 +/- 11.2; and LTB4 37.8 +/- 4.6 vs 24.6 +/- 6). These levels were all significantly decreased (p less than 0.05) by pretreatment with indomethacin except for the leukotriene LTB4, which was increased. Transient cerebral ischemia results in a reperfusion abnormality and the local generation of cyclooxygenase products, which are reduced by pretreatment with indomethacin; however, cyclooxygenase inhibition may result in increased substrate availability for the lipoxygenase system. Studies of such an interaction may lead to new understandings of the pharmacological modification of detrimental vascular changes after transient cerebral ischemia.
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PMID:Development of cyclooxygenase and lipoxygenase metabolites of arachidonic acid after transient cerebral ischemia. 300 Dec 48

The gerbil model was used to assess the therapeutic effects of the calcium antagonist nimodipine on cerebral ischemia. Transient cerebral ischemia was produced in each gerbil by bilateral common carotid occlusion of 10-, 15- or 20-min duration. Nimodipine (0.01 or 0.1 mg/kg) was administered intraperitoneally just before the carotid occlusion or 10-30 min after the removal of the arterial clips. Morbidity of each animal was evaluated using the stroke index, and the sum of stroke indices was calculated for evaluating the overall morbidity during a particular period of reperfusion. Mortality was observed for 24 hours after clip removal. Although, depending on the timing of the drug administration, the low-dose (0.01 mg/kg) nimodipine worsened the morbidity in the gerbils with 10-min ischemia, the high-dose (0.1 mg/kg) of the drug had a clear beneficial effect on the mortality associated with cerebral ischemia. These results are considered worthwhile for further trials to assess the usefulness of nimodipine as a therapeutic agent in the management of the acute ischemic stroke.
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PMID:The effect of the calcium antagonist nimodipine on the gerbil model of experimental cerebral ischemia. 373 60

Transient cerebral ischemia and stroke may occur despite previous occlusion of the artery supplying the appropriate part of the brain. After occlusion of the internal carotid artery, emboli may pass from the "stump" of the occluded artery to later produce transient cerebral ischemia or a stroke. Transient cerebral ischemia and stroke are due to a variety of conditions, some of which are strongly correlated with platelet thromboembolism, while others have little primary relation to thrombosis. The impact of this on therapeutic considerations is obvious. Thromboembolism related to myxomatous degeneration of the mitral valve (mitral valve prolapse) is a factor to consider in determining the cause of a stroke in a younger person. The prognosis for the different varieties of threatened stroke is incompletely known. When due to arteriosclerosis of the large cerebral arteries, transient cerebral ischemia and minor strokes pose a cumulative threat for a major stroke or death of 13% in the first year, 22% in the second year and 30% in the third year.
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PMID:Randomized trial of therapy with platelet antiaggregants for threatened stroke. 2: Observations on the pathogenesis and natural history of threatened stroke. 698 64

Transient cerebral ischemia was the initial manifestation of a ruptured intracranial dermoid cyst in a young adult male. The ischemia could have resulted from vasospasm caused by release of the contents of the dermoid cyst into the subarachnoid space or from other local effects of the tumor. The role of computed tomography in the evaluation of patients with transient cerebral ischemia is discussed.
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PMID:Case report. Transient cerebral ischemia as a manifestation of ruptured intracranial dermoid cyst. 732 Feb 99

Immunohistochemical changes of heat shock protein 70 (HSP 70) and glial fibrillary acidic protein (GFAP) were investigated in the gerbil hippocampus 1 h-7 days after 10 min of cerebral ischemia. Transient cerebral ischemia caused HSP 70 expression in GFAP-positive astrocytes in a delayed fashion, as compared with a rapid induction in vulnerable neurons such as hilar neurons. The present results may offer clues to elucidate the mechanisms of ischemic neuronal damage.
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PMID:Induction of heat shock protein 70 and glial fibrillary acidic protein in the postischemic gerbil hippocampus. 789 3

We examined the alterations of opioid (naloxone), N-methyl-D-aspartate and gamma-aminobutyric acidA receptors in the gerbil brain 7 days after cerebral ischemia using [3H]naloxone, [3H]MK-801 and [3H]muscimol autoradiography, respectively. We also evaluated the effect of vinconate against the alterations in these receptors. Transient cerebral ischemia was induced for 10 minutes, and vinconate (100 and 300 mg/kg) was given intraperitoneally 10 minutes before ischemia. [3H]MK-801 binding showed a more severe reduction than [3H]naloxone binding 7 days after cerebral ischemia, whereas [3H]muscimol binding was unchanged in almost all brain regions. Vinconate showed a significant prevention against the reduction in [3H]naloxone binding in all brain areas. This drug also prevented a significant reduction in [3H]MK-801 binding in most of the brain regions. Furthermore, [3H]muscimol binding in vinconate-treated gerbils exhibited a significant increase compared with that in sham-operated animals. These results show that opioid and N-methyl-D-aspartate receptors are very sensitive to transient cerebral ischemia, whereas gamma-aminobutyric acidA receptors are particularly resistant. They also suggest that vinconate has a potent protective effect against the alterations of opioid and N-methyl-D-aspartate receptors. These findings might be of interest in relation to the mechanism of ischemic neuronal damage.
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PMID:Effect of vinconate against alterations in [3H]naloxone, [3H]MK-801 and [3H]muscimol bindings after transient cerebral ischemia in gerbils. 811 27

We investigated the postischemic alterations in dopamine D1 receptor and Ca2+/calmodulin independent cyclic adenosine monophosphate (cyclic AMP) selective phosphodiesterase in gerbils and examined the effect of pentobarbital on these alterations. [3H]SCH 23390 and [3H]rolipram, respectively, were used to label dopamine D1 receptor and Ca2+/calmodulin independent cyclic-AMP selective phosphodiesterase. Transient cerebral ischemia was induced for 10 min, and pentobarbital (40 mg/kg) was administered intraperitoneally 30 min prior to ischemia. 5 h after ischemia, [3H]rolipram binding decreased significantly in the striatum and hippocampus, whereas no significant change was found in [3H]SCH 23390 binding. 7 days after ischemia, however, there was a marked reduction in both [3H]SCH 23390 and [3H]rolipram binding in the striatum and hippocampus, where histological neuronal damage was found. Pentobarbital significantly ameliorated postischemic decreases in [3H]rolipram binding both 5 h and 7 days after recirculation in most areas studied. Furthermore, this drug significantly prevented postischemic reduction in [3H]SCH 23390 binding (only) 7 days after ischemia. These results suggest that alteration of cyclic AMP selective phosphodiesterase is more sensitive at an earlier stage after ischemic insult than that of dopamine D1 receptors. Our results also demonstrate that pentobarbital reduces the alteration in [3H]SCH 23390 and [3H]rolipram binding after cerebral ischemia.
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PMID:Effect of pentobarbital on postischemic SCH 23390 and rolipram binding in gerbil brain. 822 65


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