Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Repetitive ischemia may result in more severe damage than a single similar duration insult. Inter-ischemic hypothermia significantly decreases this damage. It is unclear if protection would be evident if cooling was delayed until after the repeated insults. In this study, we evaluated the effects of 3 h of mild cooling (34-35 degrees C) beginning immediately after the third insult of ischemia, 0.5 h after the third insult and 1 h after the third insult in a gerbil model of repetitive ischemia. Neuronal damage was assessed in the cerebral cortex (CTX), hippocampus (CA1, CA4), striatum (STR), thalamus (THL), medial geniculate nucleus (MGN), and the substantia nigra reticulata (SNr). A '4-point' damage scale was used and evaluation was done in a blinded way. Group comparisons were done using the Mann-Whitney U-test for significance between the control and hypothermic groups. Immediate hypothermia after the third ischemic insult produced a significant protection in the CTX (P < 0.05), hippocampus (CA1 and CA4, P < 0.01), STR (P < 0.001), SNr (P < 0.01), MGN (P < 0.01) and THL (P < 0.01). Cooling at 0.5 and 1 h after the third insult produced no protection when compared to ischemic controls. The window of opportunity with hypothermia is narrow in repetitive ischemia. To be effective, therapy must be initiated as soon as possible after ischemic insults.
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PMID:The effect of post-ischemic hypothermia following repetitive cerebral ischemia in gerbils. 777 88

The beta-amyloid precursor protein (APP) bears characteristics of an acute-phase protein and therefore is likely to be involved in the glial response to brain injury. In the brain, APP is rapidly synthesized by activated glial cells in response to comparatively mild neuronal lesions, e.g., a remote peripheral nerve injury. Perfusion deficits in the brain result largely in neuronal necrosis and are a common condition in elderly patients. This neuronal necrosis is accompanied by a pronounced reaction of astrocytes and microglia, which can also be observed in animal models. We have therefore studied in the rat, immunocytochemically, the induction of APP after 30 min of global ischemia caused by four-vessel occlusion. The postischemic brain injuries were examined at survival times from 12 h to 7 days. From day 3 onward, APP immunoreactivity was strongly induced in the CA1 and CA4 regions of the rat dorsal hippocampus as well as in the dorsolateral striatum. In these areas, the majority of APP-immunoreactive cells were reactive glial fibrillary acidic protein (GFAP)-positive astrocytes, as shown by double-immunofluorescence labeling for GFAP and APP. Additionally, small ramified cells, most likely activated microglia, expressed APP immunoreactivity. In contrast, in the parietal cortex, APP immunoreactivity occurred focally in clusters of activated microglia rather than in astrocytes, as demonstrated by double-immunofluorescence labeling for APP and the microglia-binding lectin Griffonia simplicifolia isolectin B4. In conclusion, following global ischemia, APP is induced in reactive glial cells with spatial differences in the distribution pattern of APP induction in astrocytes and microglia.
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PMID:Glial expression of the beta-amyloid precursor protein (APP) in global ischemia. 779 Apr 14

Regional changes in the mRNA accumulations for cytoskeletal proteins alpha-tubulin and beta-actin were examined by in situ hybridization and Northern blot analysis in spontaneously hypertensive rat brains at chronic stages after 3 hours of transient ischemia. alpha-Tubulin mRNA accumulations showed no significant change at 2 weeks after transient ischemia except for a significant decrease in the frontal cortex (9.7%, p < 0.01) coinciding with ischemia induced histological changes. beta-Actin mRNA level was significantly increased in the parietal cortex (8.5%), septum (10.0%), amygdala (11.0%), CA4 area (5.8%) and the dentate gyrus (7.5%) of the hippocampus at 2 weeks after recirculation compared with a sham-operated control group (p < 0.01). The ischemic areas of hippocampal and frontocortical lesions receive afferent neurons from those regions where beta-actin mRNA was increased, suggesting that ischemia-induced increases in beta-actin mRNA may reflect actin synthesis in these neurons to compensate for lost synaptic connections. Two cytoskeletal mRNA concentrations reacted differently to cerebral ischemia, and did not parallel histological signs of ischemia either temporally or spatially.
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PMID:Regional changes in alpha-tubulin and beta-actin mRNA accumulations after transient ischemia in spontaneously hypertensive rat brains. 788 65

The mechanisms by which brain cells die after brief episodes of cerebral ischemia are not fully understood. In certain brain regions this damage may not be apparent for days. Hypothyroidism is known to decrease cerebral metabolism. We postulated that this slowing in cerebral metabolism may be neuroprotective after transient cerebral ischemia. To test this hypothesis, a total of 10 gerbils had thyroidectomies performed 2 weeks prior to ischemia. Six gerbils served as euthyroid controls. All animals were exposed to 5 min of transient ischemia and sacrificed 7 days after the insult. Silver degeneration staining was used for histological evaluation. Hippocampal damage [subiculum (P < 0.001), CA1 (P = 0. < .001), CA3 (P < 0.05), and CA4 (P < 0.001)] was significantly less in the hypothyroid animals. There was also significantly less damage in the cerebral cortex (P < 0.05) and thalamus (P < 0.05) in the hypothyroid animals. The exact mechanism of this protection is not fully understood but could be secondary to a decrease in the metabolic activity, or a reduced generation of free radicals (as is seen with protection from ischemia in kidney and liver under hypothyroid conditions). Further studies are required in order to gain a better understanding of the protective effects of hypothyroidism on cerebral ischemia.
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PMID:Hypothyroidism protects the brain during transient forebrain ischemia in gerbils. 791 Oct 86

Repeated ischemic insults at one hour intervals result in more severe neuronal damage than a single similar duration insult. The mechanism for the more severe damage with repetitive ischemia is not fully understood. We hypothesized that the prolonged reperfusion periods between the relatively short ischemic insults may result in a pronounced generation of oxygen free radicals (OFRs). In this study, we tested the protective effects of superoxide dismutase (SOD) and catalase (alone or in combination), and U78517F in a gerbil model of repetitive ischemia. Three episodes (two min each) of bilateral carotid occlusion were used at one hour intervals to produce repetitive ischemia. Superoxide dismutase and catalase were infused via osmotic pumps into the lateral ventricles. Two doses of U78517F were given three times per animal, one half hour prior to each occlusion. Neuronal damage was assessed 7 days later in several brain regions using the silver staining technique. The Mann-Whitney U test was used for statistical comparison. Superoxide dismutase showed significant protection in the hippocampus (CA4), striatum, thalamus and the medial geniculate nucleus (MGN). Catalase showed significant protection in the striatum, hippocampus, thalamus, and MGN and the substantia nigra reticulata. Combination of the two resulted in additional protection in the cerebral cortex. Compared to the controls, there was little protection in a dose of 3 mg/kg of U78517F. There was significant protection with a dose of 10 mg/kg in the hippocampus (CA4), striatum, thalamus, medial geniculate nucleus and the substantia nigra reticulata.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Superoxide dismutase, catalase, and U78517F attenuate neuronal damage in gerbils with repeated brief ischemic insults. 806 23

The neuroprotective effect of a novel anticonvulsant, zonisamide, was investigated in neonatal rats with hypoxic-ischemic brain damage. Rats underwent left carotid ligation followed by hypoxic exposure (8% O2) for 2.5 h. When zonisamide (75 mg/kg) was administered i.p. 1 h before hypoxia, it reduced the cortical infarction volume to 6 +/- 5% (mean +/- S.E.M.) from 68 +/- 7% in vehicle-treated controls and the striatal volume to 8 +/- 4% from 78 +/- 7%. Zonisamide also reduced neuronal necrosis in 5 hippocampal regions (the dentate gyrus, CA4, CA3, CA1, and the subiculum). The plasma zonisamide concentration before and after hypoxia was 47.9 +/- 2.0 microgram/ml and 42.3 +/- 3.9 microgram/ml, respectively. Epidural electrodes were implanted in 6 pups one day before hypoxia-ischemia. Electroencephalograms were recorded during hypoxia-ischemia in rats given zonisamide or vehicle before the insult. The intensity of seizure activities was similar in the zonisamide-treated pups and the vehicle-treated controls. These findings demonstrate that zonisamide reduces neonatal hypoxic-ischemic brain damage and that this protective effect does not depend on its anticonvulsant action.
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PMID:Zonisamide reduces hypoxic-ischemic brain damage in neonatal rats irrespective of its anticonvulsive effect. 808 94

We report the regional variation in relative in vivo binding of the L-type voltage sensitive calcium channel (VSCC) antagonist [3H]nimodipine to brain following transient forebrain ischemia in the rat. At 30-min of reperfusion after 20 min of forebrain ischemia, [3H]nimodipine binding was significantly increased in striatum, CA3 and CA4, and dentate relative to binding in sham-operated rats, suggesting that VSCCs were responding to ischemic depolarization. Two h following ischemia, binding in all brain structures returned to normal levels indicating repolarization of cell membranes. At 24 h of recirculation, increased [3H]nimodipine binding was again observed in striatum and dentate. Binding remained elevated in the striatum and dentate, and increased binding became evident in the CA1 region of the hippocampus after 48 h of reperfusion. With the exception of the dentate gyrus, the second rise in [3H]nimodipine binding anticipated or coincided with the observed regional ischemic cell changes. These observations in global cerebral ischemia support previous work indicating that in vivo binding of [3H]nimodipine to the L-type VSCC may be an early and sensitive indicator of impending ischemic injury. Such measurements may be of use in identifying vulnerable brain regions and defining a therapeutic window of opportunity in models of cerebral ischemia.
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PMID:In vivo binding of [3H]nimodipine in rat brain after transient forebrain ischemia. 816 82

Rats were subjected to hypoxia for 30 min in a chamber containing 5% O2 and 95% N2. The distribution of damaged neurons in the hippocampus was then examined at various predetermined times, ranging from 3 hours to 21 days after hypoxia. Hematoxylin-eosin stained sections showed shrunken and eosinophilic neurons in the CA3 and CA4 regions. Similar, but less severe, changes were also observed in the granule cell layer of the dentate gyrus. In contrast, neurons in the CA1 region were relatively resistant to hypoxia. These results showed the susceptibility of the hippocampus to hypoxia, although the affected neurons are not the same as those vulnerable to ischemia.
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PMID:Neuronal damage in the rat hippocampus induced by in vivo hypoxia. 821 9

Various studies have demonstrated increased synthesis of heat shock protein 70 (HSP70) in brain following transient ischemia, and a protective role for HSP70 against ischemic insult has been hypothesized. In this study, we determined the time course of HSP70 mRNA and HSP70 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 (pH 2.3) as a probe, the accumulation of HSP70 mRNA became evident at 4 h, and continued until 16 h, after 5 min ischemia, while it appeared at 2 h, and continued above control level until 24 h, after 30 min ischemia. In immunoblot analysis using anti-HSP70 antibody, induction of HSP70 appeared 24 h and reached a maximum level 48 h after 5 min ischemia. In immunohistochemical analysis using anti-HSP70 antibody, no staining was detected until 16 h after 5 min ischemia but staining in CA1 gradually increased from 1 day after ischemia and reached a maximum level 2 days after ischemia. Similar time profiles in staining pattern of HSP70 were observed in CA3 and CA4 neuronal cells following 30 min ischemia. Rats pretreated with 5 min ischemia (nonlethal for CA1 pyramidal neurons) were exposed to a 30 min, lethal period of ischemia, 2 days after pretreatment, at which time considerable staining of HSP70 was present. Pretreated rats had much neuronal damage in the CA1 sector less than did rats subjected to lethal, 30 min ischemia alone. These results suggest that neurons in rat hippocampus become tolerant to lethal treatment due to expression of the HSP70 gene and HSP70 protein synthesis induced by mild ischemic pretreatment.
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PMID:[Induction of HSP70 and neuronal damage following transient cerebral ischemia in rats]. 823 64

The hsp70 gene is induced by denatured protein in injured cells and is an extremely sensitive and reliable marker of cells injured by ischemia, seizures, and toxins. Normal brains have little detectable hsp70 mRNA or HSP70 protein. After status epilepticus produced by systemic injections of kainic acid, however, HSP70 protein is induced in neurons but not glia in brain regions known to be injured by kainic acid. Global and focal ischemia also induce the hsp70 gene in brain. The induction of HSP70 protein in hippocampus following increasing durations of global ischemia correlates with the regional and cellular vulnerability to ischemia: CA1 neurons express HSP70 after the briefest periods of ischemia followed by CA4, CA3, dentate granule neurons, glia, and lastly, endothelial cells. Moreover, as the severity of ischemia worsens, a transcriptional and/or translational blockade of the hsp70 gene occurs in the same order so that moderate degrees of ischemia induce HSP70 in CA3 neurons and dentate granule neurons but not necrotic CA1 neurons, and severe ischemia induces HSP70 in capillary endothelial cells of hippocampus but not in any infarcted neurons or glia throughout the hippocampus. Brief periods of focal ischemia induce HSP70 primarily in neurons, suggesting that even focal ischemia can produce selective neuronal injury without infarction. In some instances, HSP70 immunoreactive astrocytes surround the HSP70 immunostained neurons. Focal ischemia that produces infarction induces HSP70 primarily in endothelial cells of cerebral blood vessels in the regions of infarction and in neurons and astrocytes on the perimeter or the penumbral area of infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HSP70 heat shock gene regulation during ischemia. 824 24


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