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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracellular pH can be measured quantitatively in rat brain in vivo and in vitro using spectrophotometric detection of the vital dye neutral red. This method preserves spatial information and is compatible with microhistochemistry. The intracellular pH indicated by this method is in close agreement with that indicated by 31P-NMR spectroscopy. During ischemia, intracellular acidification is correlated with tissue lactate accumulation. The spatial distribution of pH values becomes more heterogeneous as the tissue becomes more acidic. Resuscitation from total cerebral ischemia produced by cardiac arrest results in rapid intracellular realkalinization. This realkalinization is at least partially inhibited by amiloride pretreatment. Some neuronal populations, especially in the hippocampal CA1 and CA4 regions, may become more acidic during ischemia and realkalinize more slowly after reperfusion than other tissue regions. The intracellular pH of hippocampal brain slice preparations is more alkaline than expected from in vivo studies. The intracellular pH of the brain slice can be acidified to near neutrality by specific inhibitors of the sodium/hydrogen ion exchanger.
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PMID:Intracellular pH in rat brain in vivo and in brain slices. 129 77

We induced repeated focal cerebral ischemia in gerbils. Single 5-min ischemia produced neuronal damage limited to the ipsilateral CA1 and CA4 hippocampus. Two 5-min ischemic insults spaced at a 1-h interval caused selective neuronal damage to the CA1, CA3 and CA4 hippocampus, striatum, neocortex, and thalamus. Three 5-min ischemic insults at 1-h intervals produced infarction. Thus, repeated focal ischemia produced cumulative brain damage by conversion of sublethal damage into selective neuronal damage and of the neuronal damage into infarction.
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PMID:Repeated focal cerebral ischemia in gerbils is associated with development of infarction. 146 95

We investigated the effects of mild and non-lethal ischemic insult on neuronal death following subsequent lethal ischemic stress in various brain regions, using a gerbil model of bilateral cerebral ischemia. Single 10-min ischemia consistently caused neuronal damage in the hippocampal CA1, CA2, CA3 and CA4, layer III/IV of the cerebral cortex, dorsolateral part of the caudoputamen and ventrolateral part of the thalamus. On the other hand, in double ischemia groups, 2-min ischemic insult 2 days before 10-min ischemia exhibited significant protection in the CA1 and CA3 of the hippocampus, the cerebral cortex, the caudoputamen and the thalamus. Five-min ischemic insult 2 days before 10-min ischemia also showed protective effect in the same areas as those of 2-min ischemia except for the CA1 region of the hippocampus, while 1-min ischemic insult exhibited no protective effect in any brain regions. In the immunoblot analysis, both 2- and 5-min ischemia caused increased synthesis of heat shock protein 72 (HSP 72) in the hippocampus, but 1-min ischemia did not. The present study demonstrated that the 'ischemic tolerance' phenomenon was widely found in the brain and also suggested that ischemic treatment severe enough to cause HSP 72 synthesis might be needed for induction of 'ischemic tolerance'.
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PMID:'Ischemic tolerance' phenomenon detected in various brain regions. 180 39

This study compared the ability of three N-methyl-D-aspartate (NMDA) receptor antagonists to prevent neuronal degeneration in an animal model of global cerebral ischemia. The model employed is characterized by damage to the striatum, hippocampus, and neocortex. Antagonists were administered to gerbils either before or after a 5-min bilateral carotid occlusion. The intraischemic rectal temperature was either maintained at 36-37 degrees C or allowed to fall passively to 28-32 degrees C. Antagonists and doses tested were 1 and 10 mg/kg of MK-801 (pre- or postischemia), 30 mg/kg of CGS 19755 preischemia, four 25 mg/kg doses of CGS 19755 administered between 0.5 and 6.5 h postischemia, and 40 mg/kg of MDL 27,266 (pre- or postischemia). All three NMDA receptor antagonists exhibited some degree of neuroprotective activity when the carotid occlusion was performed under normothermic conditions. Most of the treatments with antagonist markedly reduced striatal damage. CA1 hippocampal and neocortical pyramidal cells were spared by only three of the treatments, however, and the extent of neuroprotection varied widely from case to case. Toxic doses of antagonist were required to protect CA1 pyramidal cells from ischemic damage. Ischemic damage to hippocampal areas CA2-CA3a and CA4 appeared to be resistant to all of these treatments. Most CA1 pyramidal cells that were protected from degeneration by an NMDA receptor antagonist were histologically abnormal. The neuroprotective effects of MK-801 and intraischemic hypothermia appeared to be additive. MK-801 (10 mg/kg) consistently reduced the postischemic brain temperature, but only the magnitude of hypothermia produced soon after reperfusion correlated with its neuroprotective action. These results suggest that NMDA receptor antagonists are relatively poor neuroprotective agents against a moderately severe ischemic insult.
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PMID:Regionally selective effects of NMDA receptor antagonists against ischemic brain damage in the gerbil. 182 9

Survival, quantitative morphology of the hippocampus, cerebral tissue impedance and regional cerebral blood flow (rCBF) were studied in the Mongolian gerbil after 15 minutes of bilateral common carotid occlusion. A subgroup of animals was placed in cages with free access to running-wheels for two weeks preceding ischaemia to measure voluntary locomotor activity. Survival was enhanced in the running-wheel subgroup, with 90% of the animals still alive after 14 days as compared to 48% of the non-running group. Neuronal loss was found in all animals in the hippocampus (CA1, CA2, CA3 and CA4), and was most pronounced in the CA1 sector. In the running-wheel group, however, neuronal loss was significantly lower in sectors CA2, CA3 and CA4. The increases of cerebral impedance, which indicate ischaemic cell swelling, reached 190% in both groups during ischaemia. During postischaemic recirculation, however, impedance normalized more rapidly in the running-wheel group, indicating earlier resolution of ischaemic cell swelling. In wheel-running gerbils, postischaemic hyperperfusion evolved earlier and was more pronounced as compared to non-runners. No differences in systemic blood pressure were observed during cerebral ischaemia or thereafter.
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PMID:Electrical impedance, rCBF, survival and histology in Mongolian gerbils with forebrain ischaemia. 208 90

The purpose of this study was to examine the distribution of neuronal damage following transient cerebral ischemia in the rat model of four-vessel occlusion utilizing light microscopy as well as 45Ca-autoradiography. Transient ischemia was induced for 30 min. The animals were allowed to survive for 7 d after ischemia. In the animals subjected to ischemia, the most frequently and seriously damaged areas were the paramedian region of hippocampus, the hippocampal CA1 sector, and the dorsolateral part of striatum, followed by the inferior colliculus, the substantia nigra, the frontal cortex, and the thalamus, which were moderate damaged. Furthermore, the cerebellar Purkinje neurons, the hippocampal CA4 sector, the medial geniculate body, and the hippocampal CA3 sector were slightly affected. 45Ca-autoradiographyic study also revealed calcium accumulation in the identical sites of ischemic neuronal damage, except for the frontal cortex. Regional cerebral blood flow during 10 min of ischemia was severely decreased in selectively vulnerable areas. The blood flow in the medial geniculate body, the substantia nigra, the inferior colliculus, and the cerebellum was less pronounced than that in the selectively vulnerable areas. The present study demonstrates that transient cerebral ischemia can produce significant neuronal damage not only in the selectively vulnerable regions, but also in the brainstem.
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PMID:Neuronal damage and calcium accumulation following transient cerebral ischemia in the rat. 209 66

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.
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PMID:Effects of ischemia on multifunctional calcium/calmodulin-dependent protein kinase type II in the gerbil. 217 73

The fluorescent dye 6-methoxy-8-p-toluene sulfonamide quinoline (TSQ) was used to monitor the distribution of zinc in the hippocampus and fascia dentata of adult rats subjected to 20 min of cerebral ischemia. In normal brains TSQ stains only neuropil, in particular the mossy fiber layers in the dentate hilus (CA4) and CA3, but within 2 h after ischemia, TSQ-fluorescent cells were observed in the dentate hilus. At longer survival times TSQ-positive cells stained positively with acid fuchsin, a sign of cellular degeneration. At the same time a decrease in the TSQ fluorescence of the mossy fiber terminals in the dentate hilus (CA4) and the CA3 mossy fiber layer was noted. The observations suggest that zinc many play a role in the selective death of dentate hilar neurons after cerebral ischemia.
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PMID:Possible role of zinc in the selective degeneration of dentate hilar neurons after cerebral ischemia in the adult rat. 233 Jan 28

The pathogenesis of perinatal hypoxic-ischemic encephalopathy is poorly understood. Most insults are thought to occur before or during birth. We have investigated the evolution of parasagittal EEG activity and distribution of neuronal damage after cerebral ischemia in chronically instrumented fetal sheep (119-126 d gestation). The vertebral-carotid anastomoses were ligated and cerebral ischemia was induced by inflating occluder cuffs around the carotid arteries for 30 min. Parietal cortical EEG activity was analyzed with real-time spectral analysis with reference to control fetuses. After ischemia, EEG activity was suppressed, then rapidly increased in intensity at 8 +/- 1 h to a peak at 9 +/- 1 h postischemia. There was increased intensity of the lower frequencies (1-7 Hz) apparent as epileptiform activity with convulsions. This low-frequency hyperactivity gradually resolved by 28 +/- 7 h postinsult. After 72 h, the loss of intensity at all frequencies and laminar necrosis of the underlying parasagittal cortex indicated irreversible brain injury. Ranking the structures in order of decreasing amounts of damage: parasagittal cortex greater than hippocampal CA1, 2, and 3 regions greater than lateral cortex, hippocampal CA4 region and striatum greater than amygdala, dentate gyrus, thalamus, and cerebellum. The evolution of EEG activity and the distribution of damage after cerebral ischemia closely resembles the time course and pathology of hypoxic-ischemic encephalopathy seen in some severely asphyxiated term neonates. The consistent electrophysiologic and histologic outcome should allow this experimental approach to be valuable in testing a number of current hypotheses relating to perinatal asphyxial encephalopathy.
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PMID:Delayed seizures occurring with hypoxic-ischemic encephalopathy in the fetal sheep. 235 99

The ability of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 to prevent neuronal degeneration in the rat striatum and hippocampus caused by intracerebral injection of excitotoxins has been examined. Excitotoxic damage was assessed after 7 d, using histological and biochemical [choline acetyltransferase (ChAT) glutamate decarboxylase (GAD)] measurements. Systemically administered MK-801 was found to protect against neurodegeneration caused by NMDA (200 nmol) and the naturally occurring NMDA receptor agonist quinolinate (120-600 nmol) but not against that induced by kainate (5 nmol) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA; 50 nmol), indicating a selectivity for NMDA receptor-mediated neuronal loss. Neurotoxicity caused by NMDA (200 nmol) or quinolinate (200 nmol) was prevented by MK-801 (1-10 mg/kg, i.p.) administered in a single dose after excitotoxin injection. In the striatum, significant protection of cholinergic neurons (assessed by ChAT measurements) was observed when MK-801 was given up to 5 hr after injection of NMDA or quinolinate, whereas protection of GABAergic neurons (assessed by GAD measurements) was obtained up to 2 hr. The results suggest that GABAergic neurons degenerate more rapidly than cholinergic neurons. The competitive NMDA receptor antagonist 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonate (100 mg/kg, i.p.) gave partial protection of striatal neurons when administered 1 hr after quinolinate injection. In the rat hippocampus, administration of 10 mg/kg MK-801 i.p. 1 hr after quinolinate injection caused almost complete protection of pyramidal and granule neurons, whereas the degeneration of CA3/CA4 pyramidal neurons caused by kainate injection was unaffected. These observations indicate that neurons in rat striatum and hippocampus do not die as an immediate consequence of exposure to high concentrations of NMDA agonists but that a delayed process is involved that requires NMDA receptor activation. In this respect, intracerebral injections of NMDA agonists may mimic the pathological changes that are thought to occur in the brain following periods of cerebral ischemia, where delayed neuronal degeneration occurs.
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PMID:Neuroprotective effects of MK-801 in vivo: selectivity and evidence for delayed degeneration mediated by NMDA receptor activation. 290 93


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