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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In small animals the damaging effects of repetitive ischemia are more severe than a single insult of similar duration. Prolonged release of glutamate may correlate with the degree of damage. We report the protective effects of CGS-19755 (an N-methyl-D-aspartate receptor blocker), hypothermia or CGS-19755 in combination with mild hypothermia, in a gerbil model of repetitive ischemia. We used 3 min of forebrain ischemia and repeated it for a total of three times as 1-h intervals. Damage was assessed seven days after the insult. In the group where only CGS-19755 was used, significant neuronal protection was evident in the hippocampus (CA1 and CA3), striatum, and medial geniculate nucleus. With hypothermia significantly less damage was seen in the cerebral cortex, hippocampus (CA1 and CA4), and substantia nigra reticulata. When CGS-19755 was combined with mild hypothermia the effects of repetitive ischemia were completely abolished in all but one gerbil. Compared to hypothermia alone, significant protection was seen in the cerebral cortex, hippocampus (sibiculum, CA1 and CA4), striatum, medial geniculate nucleus, thalamus, and substantia nigra reticulata. The use of N-methyl-D-aspartate receptor blockers may protect the brain in repetitive ischemia. Combination with hypothermia may further enhance this protection.
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PMID:CGS-19755 is neuroprotective during repetitive ischemia: this effect is significantly enhanced when combined with hypothermia. 828 43

Various studies have demonstrated an increase in heat shock protein 70 (HSP70) synthesis in the brain following transiently induced ischemia, suggesting a protective role for HSP70 against ischemic insult. In this study, we determined the time course of HSP70 mRNA and protein induction in rat hippocampus following ischemia using Pulsinelli's four-vessel occlusion model, and suggested a protective role for HSP70 induction in limiting ischemic damage to neurons and delayed neuronal death. In Northern blotting analysis using human HSP70 DNA as a probe, the accumulation of HSP70 mRNA after 5 min ischemia became evident at 4 h, and continued until 16 h, while after 30 min ischemia, HSP70 mRNA appeared at 2 h, and continued above control level until 24 h after treatment. In immunoblot analysis using anti-HSP70 antibody, induction of HSP70 protein appeared 24 h and reached a maximum 48 h after 5 min ischemia. In immunohistochemical analysis using anti-HSP70 antibody, staining was not detected in CA1 neurons until 16 h after 5 min ischemia, but staining in CA1 gradually increased 1 day after ischemia and reached a maximum level 2 days after ischemia. Similar time profiles in the staining pattern of HSP70 protein were observed in CA3 and CA4 neuronal cells following 30 min ischemia. When rats pretreated with 5 min ischemia (non-lethal for CA1 pyramidal neurons) were exposed to a 30 min, lethal period of ischemia, 2 days after pretreatment, considerable staining of HSP70 was observed. Pretreated rats had much less neuronal damage in the CA1 sector than did rats subjected to lethal, 30 min ischemia alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ischemic tolerance due to the induction of HSP70 in a rat ischemic recirculation model. 836 36

The damaging effects from transient forebrain ischemia may be a result of excessive excitability or loss of inhibitory influences. In the brain, GABA acts as the major inhibitory neurotransmitter and its loss may be an important factor leading to delayed neuronal damage in the substantia nigra reticulata (SNr). In this study, we looked at the protective effects of muscimol, a GABA A agonist in a gerbil model of repetitive forebrain ischemia. For cerebral ischemia, we used three episodes of 2 min with a reperfusion period of 1 h between the insults. Histological evaluations were done 7 days after the insult using silver degeneration staining. Muscimol was infused into the third ventricle continuously for 7 days beginning just prior to the insult. There were a total of 20 animals, 12 treated with muscimol and the other 8 serving as controls. At 7 days, there was significant protection in the cortex (P = 0.007), hippocampus [CA1 (P = 0.01), CA4 (P = 0.015)], substantia nigra reticulata (P = 0.007), striatum (P = 0.049), and thalamus (P = 0.012). All statistical comparisons were done using nonparametric tests (Mann-Whitney U test). Our study shows that potentiation of inhibitory mechanisms may be important mechanisms of neuronal protection from the effects of repetitive ischemia and the effects are not limited to the SNr. Further studies are needed to better understand their mechanism of action.
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PMID:GABA agonist "muscimol" is neuroprotective in repetitive transient forebrain ischemia in gerbils. 840 90

Using in situ hybridization histochemistry, we examined changes in the cytoskeletal protein alpha-tubulin and beta-actin mRNAs in the gerbil brain 14 days after transient ischemia. In an attempt to identify the changes induced in the synthesis of cytoskeletal protein by ischemia, we also evaluated the effects of post-ischemia administration of bifemelane on these cytoskeletal proteins. alpha-Tubulin and beta-actin mRNAs were decreased in the CA1 region 14 days after transient ischemia. These decreases coincided with the loss of CA1 pyramidal cells, suggesting that they may have been related to delayed neuronal death. The beta-actin mRNA level in ischemic controls was significantly increased in the dentate gyrus, habenular nucleus, and medial and lateral thalamic nuclei, where some afferent nerves project into the hippocampal pyramidal cells. The increased beta-actin mRNA suggests that there may be a compensatory enhancement of actin synthesis in the afferent neurons that restores loosened synaptic connections with the ischemic cells in the CA1-4 fields. Administration of bifemelane just after recirculation prevented most of the ischemia-induced mRNA reductions in the CA1 field. Bifemelane's effect may be related to inhibition of Ca2+ influx and its radical scavenging activity. When bifemelane was administered to the ischemic group, alpha-tubulin mRNA levels significantly increased in the dentate gyrus and amygdaloid nucleus, and beta-actin mRNAs showed a tendency to increase in the CA3 and CA4 fields, dentate gyrus, and medial and lateral thalamic nuclei. These findings suggest that bifemelane may enhance synthesis of cytoskeletal protein, especially in the ischemic brain, inducing axon outgrowth or synapse formation.
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PMID:Ischemia-induced changes in alpha-tubulin and beta-actin mRNA in the gerbil brain and effects of bifemelane hydrochloride. 843 49

The protective effect on ischemic hippocampal damage was compared between intra- and postischemic hypothermia in Mongolian gerbils and its regional preference was evaluated. Male Mongolian gerbils were subjected to transient forebrain ischemia and the hippocampus 7 days after ischemia was examined histologically. In the intraischemic hypothermia (29-31 degrees C) group, CA1 damage was completely prevented in spite of spontaneous postischemic hyperthermia. In contrast, the same degree of brief postischemic hypothermia exerted no preventive effect. While neurons in the subiculum and CA2 sector were also protected against ischemic damage by intraischemic hypothermia, injured pyramidal neurons were always seen in the CA4 sector.
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PMID:Hypothermic prevention of the hippocampal damage following ischemia in Mongolian gerbils comparison between intraischemic and brief postischemic hypothermia. 844 93

1. The effect of transient forebrain ischemia on endothelin-1 (ET-1) and endothelin-3 (ET-3) production in the hippocampus of stroke-prone spontaneously hypertensive rats (SHRSPs) was investigated using immunohistochemical techniques. 2. In SHRSPs subjected to 10-min bilateral carotid occlusion, neuronal degeneration in the CA1 pyramidal cell layer of the hippocampus was detectable at 4 days and remarkable at 7 days after reperfusion. 3. Coinciding with neuronal degeneration, ET-1- and ET-3-like immunoreactivities were intense in the CA1 pyramidal-cell layer, the stratum lacunosum moleculare, and the CA4 subfield of the hippocampus. Almost all of the immunostained cells had morphological characteristics of astrocytes. 4. The possibility that ET has a role in the development of neuronal cell death following transient forebrain ischemia warrants further attention.
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PMID:Increased production of endothelins in the hippocampus of stroke-prone spontaneously hypertensive rats following transient forebrain ischemia: histochemical evidence. 845 60

We investigated the correlation between protection against ischemic neuronal damage by preconditioning with sublethal ischemia and the expression of heat shock protein-70 (HSP70). Three minutes of forebrain ischemia in the rat induced by four-vessel occlusion and 3 days of reperfusion was followed by 6, 8, and 10 minutes of ischemia. Seven days after the second ischemia, the brains were used for histology. Two hours, 1, 3, and 7 days after 3 or 6 minutes of ischemia, the brains were used for immunohistochemistry with an antibody raised against HSP70. Three minutes of ischemia produced no neuronal damage in the hippocampus. Six, 8, and 10 minutes of ischemia produced severe neuronal damage to CA1. However, CA1 neurons were preserved in animals subjected to 6 and 8 minutes of ischemia following preconditioning with 3 minutes of ischemia. Immunostaining showed that HSP70 was induced in the CA1 subfield 3 days after 3 minutes of ischemia. HSP70 was stained in the CA1, CA3, and CA4 subfields 1 and 3 days after 6 minutes of ischemia with or without preconditioning. However, HSP70 was also stained in CA1 2 hours and 7 days after 6 minutes of ischemia following preconditioning. These results strongly suggest that stress response induced by sublethal ischemia protects against ischemic neuronal damage. However, the protection was not seen when HSP70 synthesis was delayed. Presence of HSP70 during and immediately after ischemia may be critical for the protection against ischemic neuronal damage following preconditioning.
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PMID:[Correlation between induction of ischemic tolerance and expression of heat shock protein-70 in the rat hippocampus]. 847 66

Brief periods of forebrain ischemia result in consistent damage in the hippocampus in gerbils. This damage can be attenuated by free radical scavengers, glutamate antagonists and GABA agonists. Most of the work with cerebral protection has been done with agents infused prior to the insult. In this experiment we tested clomethiazole, a GABA agonist, as a neuroprotective agent 1 and 4 h after a 5 min ischemic insult (bilateral carotid occlusion) in gerbils. Damage was assessed using silver staining techniques at 7 days after the insult. There were 10 animals in each group. Clomethiazole was given subcutaneously at a dose of 100 mg/kg. Compared to controls, there was significant protection in the CA1 (P < 0.01) and CA4 (P < 0.01) regions of the hippocampus at 1 and 4 h after the ischemic insult. GABAergic agents may play an important role in neuronal protection when used after ischemic insults.
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PMID:Clomethiazole protects the brain in transient forebrain ischemia when used up to 4 h after the insult. 855 72

Brain damage accompanying cardiac arrest and resuscitation is frequent and devastating. Neurons in the hippocampus CA1 and CA4 zones and cortical layers III and V are selectively vulnerable to death after injury by ischemia and reperfusion. Ultrastructural evidence indicates that most of the structural damage is associated with reperfusion, during which the vulnerable neurons develop disaggregation of polyribosomes, peroxidative damage to unsaturated fatty acids in the plasma membrane, and prominent alterations in the structure of the Golgi apparatus that is responsible for membrane assembly. Reperfusion is also associated with vulnerable neurons with prominent production of messenger RNAs for stress proteins and for the proteins of the activator protein-1 complex, but these vulnerable neurons fail to efficiently translate these messages into the proteins. The inhibition of protein synthesis during reperfusion involves alteration of translation initiation factors, specifically serine phosphorylation of the alpha-subunit of eukaryotic initiation factor-2 (elF-2 alpha). Growth factors--in particular, insulin--have the potential to reverse phosphorylation of elF-2 alpha, promote effective translation of the mRNA transcripts generated in response to ischemia and reperfusion, enhance neuronal defenses against radicals, and stimulate lipid synthesis and membrane repair. There is now substantial evidence that the insulin-class growth factors have neuron-sparing effects against damage by radicals and ischemia and reperfusion. This new knowledge may provide a fundamental basis for a rational approach to "cerebral resuscitation" that will allow substantial amelioration of the often dismal neurologic outcome now associated with resuscitation from cardiac arrest.
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PMID:Global brain ischemia and reperfusion. 862 79

We examined the effect of subarachnoid administration of lidocaine on delayed neuronal damage due to forebrain ischemia in rats. Sixteen rats were divided at random into two groups: lidocaine group rats (n = 8) and control group rats (n = 8) were subarachnoidally administrated lidocaine 5mg.kg-1 and normal saline, respectively, prior to ischemia. Forebrain ischemia was induced by bilateral carotid artery occlusion combined with systemic hypotension for 10 min. Cerebral perfusion-fixation was performed 7 days after ischemia, subsequent to which the brains were sectioned coronally and stained with celestine blue/acid fuchsin. In the neocortex and the hippocampal CA4 region, the lidocaine group showed less ischemic neuronal injuries than the control group. However, in the hippocampal CA1/CA3 regions and the caudoputamen, neuronal injuries in the lidocaine group were not significantly different from those in the control group. We conclude that the pre-ischemic subarachnoid administration of lidocaine reduces the delayed neuronal damage in neocortex and hippocampal CA4 region in the rat with forebrain ischemia.
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PMID:[Subarachnoid administration of lidocaine reduces delayed neuronal damage due to forebrain ischemia in rats]. 872 95


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