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

The purpose of our experiment was to examine whether the cyclooxygenase inhibitor indomethacin ameliorates neuronal injury in the gerbil hippocampal CA1 sector following 5 minutes of forebrain ischemia. Thirty minutes before bilateral carotid artery occlusion, Mongolian gerbils were injected intraperitoneally with 1 (n = 10), 2 (n = 10), 5 (n = 12), or 10 (n = 7) mg/kg of indomethacin. Seven days after occlusion, the gerbils were perfusion-fixed and neuronal density in the hippocampal CA1 sector was assessed. The mean +/- SEM neuronal density in nine unoperated normal gerbils was 307 +/- 9/mm, in 10 untreated ischemic gerbils 55 +/- 21/mm, and in seven vehicle-treated ischemic gerbils 15 +/- 9/mm. The mean +/- SEM neuronal density in ischemic gerbils treated with 1, 2, 5, or 10 mg/kg indomethacin was 132 +/- 28/mm, 154 +/- 29/mm, 176 +/- 30/mm, and 136 +/- 39/mm, respectively. Indomethacin at any dose significantly ameliorated ischemic neuronal damage in the gerbil hippocampal CA1 sector.
Stroke 1988 Nov
PMID:Indomethacin ameliorates ischemic neuronal damage in the gerbil hippocampal CA1 sector. 318 24

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

We studied the xanthine derivative propentofylline (HWA 285) to determine its protection against ischemic brain damage when administered before and after ischemia. Transient forebrain ischemia was produced in 81 Mongolian gerbils by occluding both carotid arteries. The necessary surgery was performed under anesthesia with intraperitoneal pentobarbital/chloral hydrate 2 days before occlusion. We tested the parameters delayed selective hippocampal nerve cell damage, generation of seizures, and survival. Determination of the dose-response relation revealed the optimal dose of HWA 285 to be 10 mg/kg i.p. The effect of the drug on delayed selective nerve cell damage in the hippocampus was assessed by measuring the intensity of Nissl staining in the CA1 area by means of densitometry 4 days after a 10-minute occlusion. Gerbils treated with HWA 285 revealed significant protection of the CA1 neurons even when the drug was applied 1 hour after the end of the occlusion. In contrast to HWA 285, pentobarbital provided no detectable protection of the CA1 neurons in our experimental model when administered 1 hour after occlusion, suggesting different mechanisms of action. After a 15-minute occlusion, all six untreated gerbils developed convulsions and died within 2 days. Chronic (daily) treatment of nine gerbils with HWA 285 prevented the generation of convulsions in eight and allowed seven to survive for greater than 12 days.
Stroke 1988 Dec
PMID:Protection against ischemic brain damage using propentofylline in gerbils. 320 13

Induction of the 70-kDa heat shock protein, hsp70, has been demonstrated in brain following experimental stroke. In the present study, hsp70 was localized in gerbil brain at intervals after transient ischemia using a monoclonal antibody specific for stress-inducible forms of hsp70-related proteins. Induced immunoreactivity was found only in neurons, primarily in hippocampus, striatum, entorhinal cortex and some neocortical regions. Notably hsp70 accumulation was minimal in hippocampal CA1 neurons which die after brief ischemic episodes, but was most pronounced in dentate granule cells and CA3 neurons which are spared. The peak of CA3 immunoreactivity occurred at 48-h recirculation, at the onset of CA1 neuron loss at 2-4 days, demonstrating that hsp70 induction is also a component of this delayed hippocampal pathophysiology rather than a direct response to the metabolic disruption of the initial ischemic episode. These results suggest that hsp70 immunocytochemistry may serve as a marker for neuronal circuitry involved in proposed excitotoxic mechanisms after ischemia and other stresses. Control animals showed immunoreactivity in ependymal cells lining the ventricles, indicating a role for hsp70 in normal functioning of these specialized cells.
 ...
PMID:Localization of 70-kDa stress protein induction in gerbil brain after ischemia. 322 11

In vivo models of cerebral ischemia do not fully control for the interacting effects of many variables (e.g., anesthesia, temperature, cerebrovascular changes) and often do not clearly define the region affected. Numerous in vivo studies have indicated that hyperglycemia augments ischemic brain damage; this effect is often attributed to lactic acidosis. To separate the effects on neuronal tissue of ischemia from those due to actions on the cerebrovascular system, we used an in vitro blood-free system as an ischemic model. In our study we evaluated the effects of various combinations of oxygen and glucose levels on evoked synaptic activity in the CA1 region of the rat hippocampal slice preparation. A 50% inhibitory dose for both oxygen and glucose on neuronal synaptic function was determined. It is our intention to use this model for preliminary screening of antihypoxic/anti-ischemic drugs.
Stroke 1988 Apr
PMID:The rat hippocampal slice preparation as an in vitro model of ischemia. 336 78

U74006F (21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-16 alpha-methylpregna-1,4,9(11)-triene-3,20-dione, monomethane sulfonate) is a novel and potent inhibitor of central nervous system tissue lipid peroxidation that is devoid of classical steroid hormonal activities. Its possible efficacy in attenuating postischemic mortality and neuronal necrosis was examined in gerbils following 3-hour unilateral carotid artery occlusion. Male Mongolian gerbils received two intraperitoneal injections of either vehicle or U74006F (3 or 10 mg/kg), the first injection 10 minutes before and the second injection at the end of the 3-hour ischemic episode. In an initial series of experiments, vehicle-treated gerbils displayed 60.9% (14 of 23) survival 24 hours after ischemia, which decreased to 34.8% (8 of 23) at 48 hours. In contrast, the 10 mg/kg U74006F-treated group showed 86.7% (13 of 15) survival at 24 hours (p less than 0.15 vs. vehicle) and 80.0% (12 of 15) survival at 48 hours (p less than 0.02). In a second series, neurons in the hippocampal CA1 subfield and the medial and lateral cerebral cortex were counted in gerbils surviving 24 hours after unilateral carotid artery occlusion. Comparison of neuronal densities in the ischemic hemisphere with those in the contralateral nonischemic hemisphere revealed significant neuronal preservation in all three brain regions of 10 mg/kg i.p. x 2 U74006F-treated gerbils. Our results show that U74006F can improve survival and attenuate neuronal necrosis in a severe brain ischemia model.(ABSTRACT TRUNCATED AT 250 WORDS)
Stroke 1988 Aug
PMID:21-Aminosteroid lipid peroxidation inhibitor U74006F protects against cerebral ischemia in gerbils. 340 Jan 11

Sixty-five male gerbils were exposed to 30 minutes of cerebral ischemia induced by a bilateral carotid artery occlusion. One group of 15 gerbils received a single injection of 25 microliter of 5 microM cyclohexyladenosine into the cerebral ventricle 15 minutes after release of the occlusion. Another group of 45 gerbils received a similar injection of the vehicle. Five days after ischemia, the hippocampal histology was examined under light microscopy. In the gerbils treated with the adenosine receptor agonist N-6-cyclohexyladenosine, the CA1 region of the hippocampus showed significant quantitative pyramidal cell preservation (p less than 0.01, Mann-Whitney U test). Qualitatively, substantial destruction of CA1 neurons was present in all hippocampi of the vehicle-injected gerbils. The CA1 neurons in the cyclohexyladenosine-treated gerbils did not differ from those seen in the five nonischemic controls. The precise mechanism of the protective action of cyclohexyladenosine is unknown, although it has been demonstrated that adenosine agonists reduce presynaptic glutamate release in vitro. It is possible that postischemic administration of cyclohexyladenosine decreases the release of this neurotransmitter in the intact brain as well. The concomitant reduction of the neurotoxic effect of glutamate may, therefore, result in better histologic preservation of the pyramidal cells in the postischemic CA1.
Stroke 1988 Sep
PMID:Cyclohexyl adenosine protects against neuronal death following ischemia in the CA1 region of gerbil hippocampus. 341 11

Adult male gerbils were submitted to 5-minute cerebral ischemia by bilateral carotid artery occlusion. At the end of ischemia and at various recirculation times ranging from 15 to 120 minutes, brains were frozen in situ and the regional distribution of ATP, glucose, and tissue pH was studied on coronal cryostat sections by bioluminescent and fluoroscopic techniques. During ischemia ATP was completely depleted, glucose decreased to less than 10% of control, and regional tissue pH decreased from 7.04-7.09 to about 6.0. After the beginning of recirculation tissue pH and the regional content of metabolites exhibited a triphasic course. After 15 minutes pH returned to or even above normal, and ATP- and glucose-induced bioluminescence normalized. However, there was a secondary deterioration of both tissue acidosis and the metabolic state after 30 minutes. After longer recirculation times changes again improved and returned to normal within 2 hours. These changes were similar in all brain regions with the exception of the CA1 sector of the hippocampus, where the transient normalization of tissue pH was absent after 15 minutes of recirculation. This finding is in line with the previously observed microcirculatory insufficiency of this area and demonstrates that the CA1 sector of the hippocampus suffers more pronounced postischemic acidosis than other less vulnerable regions of the brain.
Stroke
PMID:Effect of 5-minute ischemia on regional pH and energy state of the gerbil brain: relation to selective vulnerability of the hippocampus. 356 98

[14C]Palmitate was injected intravenously in awake gerbils at various times after 5 minutes of bilateral carotid artery occlusion or a sham operation. Regional rates of incorporation of plasma palmitate into the hippocampus and other regions of the anterior circulation were determined relative to the mean rate of incorporation into regions of the posterior circulation using quantitative autoradiography and a ratio method of analysis. One day after bilateral carotid occlusion, relative palmitate incorporation was elevated significantly by 16% in the CA4 pyramidal cell layer and by 20% in the dentate gyrus of the hippocampus compared with sham-operated gerbils. At 3 days, significant elevations of this magnitude were found in the CA3 and CA4 cell layers, whereas relative incorporation was reduced by 26% in the CA1 pyramidal cell layer. At 7 days, the only significant difference from control was a 15% elevated incorporation in the CA3 pyramidal cell layer. Histologic examination indicated substantial cell death in the CA1 pyramidal layer at 3 days, with extensive glial reaction and phagocytic invasion at 7 days. Our results suggest that the turnover of palmitate-containing lipids is reduced in the CA1 layer of the gerbil hippocampus but that lipid synthesis is stimulated in hippocampal regions (CA3, CA4, dentate gyrus) affected by but recovering from transient bilateral carotid occlusion.
Stroke
PMID:Regional cerebral palmitate incorporation following transient bilateral carotid occlusion in awake gerbils. 368 87

The Mongolian gerbil is known to develop delayed neuronal death in the hippocampus following brief forebrain ischemia (Brain Res 239: 57-69, 1982). The effect of pentobarbital on this slow process of neuronal damage was examined. Immediately following 5 min of bilateral carotid occlusion, pentobarbital (10, 20, or 40 mg/kg) was injected. The control animals received saline injection. Seven days following ischemic insult, animals were perfusion-fixed and the neuronal density in the hippocampal CA1 subfield was counted. Most of the neurons in the CA1 sector survived ischemic insult when pentobarbital was given, whereas most of control group neurons were lost without the treatment. The average neuronal density of 20 mg/kg group was 168.2 +/- 12.3 (SEM) per 1 mm linear length of the CA1 subfield. The density in 40 mg/kg group was 181.1 +/- 14.9. The neuronal density in the whole control group was 34.3 +/- 5.1. The density of unoperated normal gerbils was 212.3 +/- 3.9. This result indicates that the neuronal damage of "delayed neuronal death" is reversible. On the other hand, when pentobarbital was injected 1 hr following ischemia, it showed no effect. The cell change in the CA1 sector, reversible at the initial stage, seems to rapidly become irreversible, while neurons still remain intact morphologically.
Stroke
PMID:A reversible type of neuronal injury following ischemia in the gerbil hippocampus. 371 42


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