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

We investigated the effect of mild (34 degrees C) postischemic hypothermia on hippocampal neuronal damage in 43 rats as a function of the duration of forebrain ischemia. Two temperatures and two durations were investigated. In two normothermic groups ischemia lasted 8 (n = 15) and 12 (n = 10) minutes, respectively. In two hypothermic groups ischemia lasted 8 (n = 9) and 12 (n = 9) minutes, respectively, and was followed immediately by the lowering and maintenance of rectal temperature to 34 degrees C for 2 hours. Seven days after the ischemic insult, the rats were sacrificed and the brains were prepared for histologic analysis; the percentage of necrotic neurons among the total neuronal population in selected CA1/2 sectors of the hippocampus was determined. There was a significant decrease in the percentage of necrotic neurons in the central (77.5% versus 55.5%, p = 0.006) and lateral (62.5% versus 38.9%, p=0.005) areas and in the overall CA1/2 sector of the hippocampus (71.8% versus 52.2%, p = 0.008) for the 8-minute hypothermic group compared with the 8-minute normothermic group. In contrast, no differences were detected in any area of the hippocampus between the 12-minute normothermic and the 12-minute hypothermic groups (p = 0.29-0.49). Our data indicate that mild postischemic whole-body hypothermia ameliorates neuronal survival when ischemia lasts 8 minutes but not 12 minutes.
Stroke 1991 Jan
PMID:Mild hypothermic intervention after graded ischemic stress in rats. 198 71

Twenty-four hour postischemic neuronal necrosis was compared in male vs. female Mongolian gerbils subjected to a 3-h period of severe incomplete hemispheric ischemia produced by unilateral carotid occlusion. The incidence of stroke-prone males was 42.9% versus 26.7% for the females. Among the stroke-prone animals, the males displayed significantly greater neuronal necrosis at 24 h after ischemia compared to the females in the cerebral cortex and CA1 region of the hippocampus. In the CA1 region of the stroke-prone males, only 2.0% of the normal neuronal population remained by 24 h compared to 36.8% in the stroke-prone females (p less than 0.02). In the cerebral cortex, the males had only 19.9% of normal versus 58.2% in the females (p less than 0.05). In a second series of mechanistic experiments, no differences in cortical blood flow (CBF) were disclosed between preselected male and female stroke-prone animals before, during, or for 2 h after ischemia. As with the CBF, the extent of cortical extracellular hypocalcia during ischemia did not differ significantly. However, the degree of postischemic recovery of cortical extracellular calcium was significantly better in the females from 30 min to 2 h after reperfusion. In the same experiments, hemispheric vitamin E levels were measured at the 2 h time point as an index of postischemic brain lipid peroxidation. No difference in baseline vitamin E levels was observed between male and female sham-operated gerbils. In the males subjected to 3 h of ischemia plus 2 h of reperfusion, the hemispheric vitamin E decreased by 43.5% compared to the sham-operated males.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sex differences in postischemic neuronal necrosis in gerbils. 199

Using proton and phosphorus magnetic resonance spectroscopy, we evaluated the metabolic effects of preischemic administration of the N-methyl-D-aspartate antagonist dextromethorphan (50 mg/kg i.p.) during global forebrain ischemia and subsequent reperfusion in rats. Dextromethorphan-treated animals (n = 10) showed less lactate formation during ischemia than untreated animals (n = 11, p less than 0.001). During reperfusion, the lactate level in the treated group was reduced (p less than 0.05). Tissue pH declined less in the treated group during ischemia (p less than 0.01). There was no difference in the phosphocreatine/inorganic phosphate peak height ratio between groups. During ischemia, the N-acetylaspartate resonance peaks decreased in both groups. Histologic damage assessed in the hippocampal CA1 region 7 days after the ischemic insult was more severe in the untreated group (p less than 0.05). There was a significant correlation between end-ischemic tissue pH and hippocampal damage (r = -0.73, p less than 0.05). In the dextromethorphan-treated animals, 90% of the rats survived compared with 47% of the untreated animals (p less than 0.05). These results support findings in previous studies that dextromethorphan attenuates ischemic damage.
Stroke 1991 Mar
PMID:Effects of dextromethorphan on rat brain during ischemia and reperfusion assessed by magnetic resonance spectroscopy. 200 3

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

Induction of messenger RNA encoding the 70-kDa heat shock or stress protein, hsp70, and the product of the proto-oncogene c-fos was evaluated in gerbil hippocampus by in situ hybridization at various recirculation intervals after 5 minutes of ischemia. Striking increases in c-fos RNA were observed in dentate granule cells within 15 minutes of recirculation and remained evident through 1 hour, returning to undetectable control levels by 3 hours. Modest c-fos hybridization was seen in CA1 and CA3 neurons during the same time course. These results are consistent with the rapid and transient stimulation-induced c-fos expression observed in many experimental systems. Hsp70 expression showed a longer time course, being strongly induced in all major hippocampal neuron populations within 3 hours and persisting for approximately 12 hours in dentate granule cells and through 24 hours in CA3 pyramidal neurons. Notably, the most prolonged expression of hsp70 RNA was observed in vulnerable CA1 neurons that minimally accumulate the immunoreactive protein, with hybridization detected essentially until the death of this cell population at 3-4 days. These studies demonstrate an overlapping distribution of hsp70 and c-fos expression in gerbil hippocampus after ischemia, although there are differences in time course and in the relative induction observed in different neuron populations. The transient increase in c-fos hybridization in dentate granule cells is identical to that seen in various seizure paradigms and provides further support for activation of hippocampal circuitry after ischemia. The prolonged time course of hsp70 messenger RNA expression in vulnerable CA1 neurons may provide a molecular correlate of proposed excitotoxic mechanisms mediating delayed neuronal death.
Stroke 1990 Nov
PMID:70-kDa heat shock protein and c-fos gene expression after transient ischemia. 212 54

The protective roles of Ca2+ channel blockers against ischemic hippocampal damage are still debated. We used autoradiography to study postischemic L-type Ca2+ channels (1,4-dihydropyridine Ca2+ channel blocker binding), adenosine A1 receptors, and muscarinic cholinergic receptors in the rat hippocampus using [3H]PN200-110 (PN), [3H]cyclohexyladenosine (CHA), and [3H]quinuclidinyl benzilate (QNB), respectively, in 49 rats subjected to 20 minutes of forebrain ischemia. The rats were decapitated after 1 (n = 7), 3 (n = 7), 6 (n = 8), 12 (n = 7), 24 (n = 6), 48 (n = 6), or 168 (n = 8) hours of recirculation; eight control rats were sham-operated but experienced no cerebral ischemia. Reduced receptor binding preceding the delayed death of CA1 pyramidal cells was first observed in the stratum oriens of the CA1 subfield. Significant reductions in [3H]PN, [3H]CHA, and [3H]QNB bindings of this stratum compared with control were noticed after 3 (35%, p less than 0.01), 12 (31%, p less than 0.01), and 1 (10%, p less than 0.05) hours of recirculation, respectively. By 168 hours after ischemia (when the populations of CA1 pyramidal cells were depleted) all strata in the CA1 subfield had lost most of their receptor sites, and [3H]PN, [3H]CHA, and [3H]QNB bindings in the stratum oriens were decreased to 23%, 30%, and 63% of control (p less than 0.01). Although [3H]PN binding in the CA3 subfield did not change significantly during 168 hours after ischemia, the histologically intact dentate gyrus exhibited a 31% loss of binding sites compared with control (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Stroke 1990 May
PMID:Calcium antagonist, adenosine A1, and muscarinic bindings in rat hippocampus after transient ischemia. 214 Feb 13

There is a net movement of calcium into brain cells during anoxia and ischemia. This communication examines the mechanisms of this movement in rat hippocampal slices by analyzing changes in 45Ca2+ distribution. The CA1 pyramidal cells are the most sensitive to anoxic/ischemic damage; therefore, our measurements of Ca2+ and high-energy nucleotides are restricted to this region. The increase in intracellular Ca2+ levels during anoxia is not blocked by the Ca2+ channel blocker cobalt, nor is it blocked by N-methyl-D-aspartate receptor antagonists kynurenic acid, D-2-amino-5-phosphonovaleric acid, or ketamine. Kinetic measurements show that the rate of Ca2+ efflux across the plasmalemma during anoxia is sufficiently decreased to account for the increase in intracellular Ca2+. It thus appears that the net increase in calcium does not result from the opening of voltage-sensitive Ca2+ channels, nor from flux through the N-methyl-D-aspartate channel. Rather, it results from inhibition of the adenosine triphosphate-dependent extrusion mechanism for Ca2+. The relation of this conclusion to mechanisms of anoxic cell damage is discussed.
Stroke 1990 Nov
PMID:Mechanisms of intracellular calcium accumulation in the CA1 region of rat hippocampus during anoxia in vitro. 214 81

The activation of 5-hydroxytryptamine receptors exerts an inhibitory influence on neuronal activity in a way similar to the activation gamma-amino-n-butyric acid and adenosine A1 receptors. Therefore, we hypothesized that 5-HT1A-receptor agonists might exert a neuroprotective effect. We tested the full agonists Bay R 1531 and 8-OH-DPAT and the partial agonists ipsapirone and gepirone in the model of transient global ischemia in the Mongolian gerbil. Ipsapirone protected 53% of pyramidal neurons (p less than 0.05) in the CA1 area of the hippocampus from ischemic damage at a dose of 3 mg/kg. Bay R 1531 showed a powerful neuroprotective effect with 100% preservation of neurons at a dose of 3 mg/kg (p less than 0.001) while gepirone and 8-OH-DPAT were ineffective. These findings suggest that 5-HT1A-receptor agonists might be effective tools for the therapy of cerebral ischemia. However, the varying results indicate that transient forebrain ischemia in the gerbil may not be the optimal model system to demonstrate clearly the neuroprotective activity of these compounds.
Stroke 1990 Dec
PMID:Effects of 5-hydroxytryptamine1A-receptor agonists on hippocampal damage after transient forebrain ischemia in the Mongolian gerbil. 214 36

Cerebral ischemia produces a disruption of calcium homeostasis in neurons. This may explain the extreme sensitivity of these cells to ischemic insult. Prolonged increases in calcium levels may produce irreversible damage to the cell by altering important calcium-dependent enzyme systems such as calcium/calmodulin-dependent protein kinase II. Five minutes of acute forebrain ischemia in the gerbil produced a significant decrease in calcium/calmodulin-dependent protein kinase II activity as early as 10 seconds postischemia and persisting up to 7 days after insult. Because hypothermia protects against ischemia-induced cell death in the gerbil, we examined the effect of ischemia on cell death and calcium/calmodulin-dependent protein kinase II at different intracerebral temperatures: hyperthermia (39 degrees C), normothermia (36 degrees C), and hypothermia (32 degrees C). In ischemic animals, hyperthermia produced severe loss of neurons in CA1 and moderate loss in CA3-CA4 subregions. Normothermia in ischemic animals produced severe loss of neurons in the CA1 subregion. Hypothermic ischemic animals showed no significant loss of neurons in any hippocampal region. Ischemia produced a severe decrease (17 +/- 6% of control) in calcium/calmodulin-dependent kinase II activity in hyperthermic animals, a moderate decrease (55 +/- 15% of control) in normothermic animals, and no decrease of enzyme activity in hypothermic animals. Thus, lowering and raising intracerebral temperature decreased and increased, respectively, the extent of ischemia-induced damage in the gerbil. Because ischemia-induced effects on calcium/calmodulin-dependent protein kinase II activity are rapid and long-lasting, hypothermia may protect through preservation of calcium/calmodulin-dependent protein kinase II activity.
Stroke 1990 Nov
PMID:Effects of ischemia on multifunctional calcium/calmodulin-dependent protein kinase type II in the gerbil. 217 73

Previous therapeutic studies on the prevention of selective vulnerability of neurons in the hippocampus have suggested that the critical period for induction of delayed neuronal injury occurs early during recirculation. To determine the onset and duration of this period, an ultrashort-acting barbiturate (methohexital) was infused into the left carotid artery of 47 gerbils after various times of recirculation following 10 minutes of bilateral forebrain ischemia. Neuronal density in the left CA1 sector was determined 7 days later by counting the number of surviving neurons per millimeter of pyramidal cell layer. In 16 saline-treated gerbils, less than 10% of the CA1 neurons survived the 10 minutes of ischemia. Postischemic carotid infusion of methohexital improved neuronal survival, the degree of improvement depending on the timing and duration of the methohexital infusion. When carried out during the initial 40 minutes of recirculation, methohexital infusion for 10 minutes increased the number of surviving neurons to approximately 60% of that in five sham-operated control gerbils. This increase was significant for infusions carried out between the 10th and 20th minutes (n = 6, p less than 0.05) and between the 30th and 40th minutes (n = 6, p less than 0.05) of recirculation. Methohexital infusion for 20 minutes increased neuronal survival to 95% and 73% of that in the controls when carried out between the 0th and 20th minutes (n = 5, p less than 0.005) and between the 20th and 40th minutes (n = 5, p less than 0.005) of recirculation, respectively. Protection was nonsignificant for 10- or 20-minute methohexital infusions carried out after the 40th minute of recirculation. Our results demonstrate that the pathologic processes leading to delayed neuronal injury in the CA1 sector are induced during the initial 40 minutes of recirculation and that barbiturates are able to reverse these processes only if given during this period.
Stroke 1990 Oct
PMID:Therapeutic window of CA1 neuronal damage defined by an ultrashort-acting barbiturate after brain ischemia in gerbils. 221 15


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