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

The role of cytoskeletal damage in the disruption of the plasma membrane observed during myocardial ischemia has been studied using antibodies to vinculin to identify changes in the distribution of this membrane associated cytoskeletal protein. Vinculin is a component of the cytoskeletal attachment complex between the plasma membrane and the Z-line of the underlying myofibrils. The effects of varying periods of total ischemia on the localization of vinculin were assessed by immunofluorescence and evidence of membrane disruption was evaluated by electron microscopy. Thin tissue slices prepared from the ischemic tissue were incubated in oxygenated Krebs-Ringer phosphate buffer at 37 degrees C to assess inulin permeability, ultrastructure, and any changes in the distribution of vinculin associated with incubation. The previously reported costameric pattern of vinculin staining was observed in longitudinal sections of control myocardium, myocardium subjected to 60 minutes of total ischemia, and myocardium subjected to 60 minutes of ischemia followed by 60 minutes of incubation in oxygenated media. Electron microscopy and inulin permeability measurements confirmed that plasma membrane integrity was preserved under these conditions. However, when the duration of total ischemia was extended to 120 minutes or longer, there was a progressive loss of vinculin staining along the lateral margin of myocytes. This change correlates with the appearance of subsarcolemmal blebs and breaks in the plasma membranes observed by electron microscopy and confirmed by the increase in inulin permeability observed in tissue slices.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytoskeletal damage during myocardial ischemia: changes in vinculin immunofluorescence staining during total in vitro ischemia in canine heart. 243 27

Transient forebrain ischemia is followed within minutes by accelerated proteolysis of the cytoskeletal protein, spectrin. This effect is most pronounced in the selectively vulnerable CA1 region of hippocampus which also experiences a second proteolytic phase during the terminal stages of neuronal degeneration. Both proteolytic phases are suppressed by MK-801, an NMDA receptor antagonist. Cytoskeletal disruption, via NMDA receptor-linked proteolytic events, is suggested to predispose vulnerable neurons to delayed cell death.
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PMID:Ischemia triggers NMDA receptor-linked cytoskeletal proteolysis in hippocampus. 254 56

We have previously demonstrated that transient cerebral ischemia induces marked decreases in concentrations of cytoskeletal proteins and have suggested putative involvement of calpain in the decrease of microtubule-associated protein 2 (MAP2) content. We examine the effect of nilvadipine, a new calcium channel blocker, on protein degradation in gerbil brains after 5 minutes of bilateral carotid artery occlusion and compare this effect with those of nimodipine and nicardipine. By densitometric quantification of the electrophoretically separated soluble proteins, mean +/- SEM MAP2 content in the hippocampus (14.4 +/- 1.8 micrograms/mg protein) was depleted (5.4 +/- 0.5 micrograms/mg, p less than 0.01) 4 days after ischemia; this depletion was significantly inhibited by 1 or 10 mg nilvadipine/kg/day. MAP2 content was also depleted in vitro when normal nonischemic brain extract was incubated with calcium, but this degradation was not inhibited by the calcium channel blockers. Our results suggest that calcium channel blockers do not act directly on calpain but act at the calcium channels of neurons and may suppress activation of the enzyme and attenuate ischemic degradation of cytoskeletal protein. We found nilvadipine to be the most potent drug among those studied, and we believe it could be useful for the treatment of cerebral ischemia.
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PMID:Nilvadipine attenuates ischemic degradation of gerbil brain cytoskeletal proteins. 291 39

Methods are described for determining the expression of specific mRNAs and proteins in brain slices, in order to elucidate changes in gene expression during preparation of vibratome slices from hippocampus of adult rats. In situ hybridization with 35S-labeled oligonucleotides was used to evaluate the level and distribution of c-fos and hsp72 mRNAs in 15-microns frozen sections prepared from these slices. Commercially available antibodies were used to examine the distribution of induced Fos and Jun proto-oncogenes as well as expression of the neuronal cytoskeletal protein, microtubule-associated protein 2 (MAP2), in 50-microns vibratome sections from immersion-fixed slices. These studies confirm the induction of c-fos and hsp72 mRNAs during routine incubation, as previously observed in hippocampal slices obtained with a tissue chopper and incubated under somewhat different conditions, indicating that such responses are likely to be common features of many slice preparations. Accumulation of Fos and Jun immunoreactivities in neurons and glia was generally consistent with the distribution of c-fos mRNA induction observed in slices, and the neuronal component of this response was comparable to the expression of these proteins observed after transient ischemia in vivo. MAP2 immunoreactivity detected in the dendritic processes of neurons tended to show an increase in staining intensity during slice incubation, although loss of dendritic staining in specific regions was occasionally observed in association with the absence of Fos and Jun expression and histological evidence of neuron damage. These results support the use of MAP2 immunoreactivity as a sensitive indicator of neuronal integrity in slices.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunocytochemical and in situ hybridization approaches to the optimization of brain slice preparations. 747 55

The time course of mRNA expressions of two cytoskeletal proteins, beta-actin and alpha-tubulin, was studied by Northern blot analysis and in situ hybridization in the same gerbil brains at various periods of recirculation following 10 min of forebrain ischemia. On Northern blot analysis, beta-actin mRNA in the forebrain showed increase after 6 h and 24 h recirculation. There was wide variation in its expression 3 days postischemia (PI), and by 7 days PI it had returned to control. The alpha-tubulin mRNA in the forebrain was shown to be reduced 6 h PI in our previous study. In the present analysis of Northern blots of delayed postischemic periods, there was no significant change in its expression even though there were variations. In situ hybridization revealed a decline in the mRNA expressions of both alpha-tubulin and beta-actin in the CA1 region as early as 6-24 h PI with the reductions being prominent at 3 days PI. By 7 days PI, beta-actin was only faintly visible while alpha-tubulin was completely absent in the CA1 region. Neither RNA was detectable in CA1 1 month PI. The heat shock-70 protein was expressed by 1 h PI, and it continued to be expressed up to 24 h, returning to control by 3 days PI. These results indicate that ischemia inhibits mRNA expressions of cytoskeletal protein in the selectively vulnerable region of the brain, i.e. CA1. The time course of the reduction of the two mRNAs coincides with delayed neuronal death suggesting that the cytoskeletal proteins may play important roles in selective postischemic neuronal injury.
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PMID:Expression of beta-actin and alpha-tubulin mRNA in gerbil brain following transient ischemia and reperfusion up to 1 month. 760 36

The present study examined the immunoexpression of the neuronal cytoskeletal proteins, MAP-2 and beta-tubulin within a timed series of rat fetal neocortical transplants. beta-tubulin is a major component of microtubules and MAP-2 regulates the assembly and stability of neuronal microtubules and is a major site for the phosphorylation cAMP dependent protein kinase in neurons. Both proteins are strongly expressed in the soma and dendrites of normal neurons. MAP-2 has been shown to be a sensitive marker for ischemia in neurons and is downregulated in this form of injury. Immunoexpression of both MAP-2 and beta-tubulin in grafted cortical neurons was markedly reduced when compared to age-matched or even perinatal specimens at all post-operative times. Dendritic staining was confined to random, thin processes with no laminar patterns and staining within somata was very weak. In some specimens, somatic expression was increased and dendrites were more robustly stained when a portion of the graft was juxtaposed to a fiber tract even though in other regions of the same graft there was very weak immunostaining. The present results corroborate previous studies of cortical transplants indicating an immature structure and metabolism, and it is suggested here that the primary factor is a sublethal form of ischemic injury. Another possibility for the relative paucity of cytoskeletal protein expression could be that transplanted neurons undergo a new developmental scheme (neodevelopment) that is brought about by truncated migration patterns and abnormal synaptic connections.
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PMID:Diminished expression of microtubule-associated protein (MAP-2) and beta-tubulin as a putative marker for ischemic injury in neocortical transplants. 772 37

One of the most prominent phenomena that occurs during the early phase of cerebral ischemia has been shown to be the immunohistochemical collapse of cytoskeletal proteins. Among these, microtubule-associated protein 2 (MAP 2) has been shown to be vulnerable to ischemic injuries. In order to select a suitable volatile anaesthetic from the standpoint of cytoskeletal protein breakdown during cerebral ischemia, we compared the effect of isoflurane, halothane and sevoflurane on MAP 2 degradation during 20 min of forebrain ischemia in the rat. Under 1 MAC of three volatile anesthetics, forebrain ischemia was induced by the occlusion of the bilateral common carotid artery combined with a lowering of mean arterial pressure to 50 mmHg. Immediately after cerebral ischemia, four regions of the brain, the frontoparietal cortex, brainstem, hippocampus and cerebellum, were removed separately and homogenized. Subsequently, MAP 2 from each region was quantitatively measured using an enzyme-linked immunosorbent assay. MAP 2 in the frontoparietal cortex and hippocampus was significantly protected from degradation with isoflurane anaesthesia more than with halothane and sevoflurane anaesthesia.
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PMID:[Effects of volatile anesthetics on microtubule-associated protein 2 degradation during forebrain ischemia in the rat]. 783 96

Although specific patterns of cellular vulnerability have been identified in experimental models of cerebral ischemia, there is little data on the occurrence of similar abnormalities in human ischemia. We therefore used a variety of histochemical methods to define changes affecting specific classes of cells in post-mortem specimens from seven patients with hippocampal and neocortical ischemic lesions. In acute lesions, staining with SMI-32, an antibody directed against nonphosphorylated neurofilaments that labels pyramidal projection neurons, was prominently depleted even when conventional Nissl staining revealed only mild pyknosis. In contrast, staining for other markers such as microtubule-associated protein 2 (MAP-2), another cytoskeletal protein, or parvalbumin, a calcium-binding protein found in gamma-aminobutyric acid (GABA)-ergic interneurons, were relatively preserved. SMI-32 antibody also labeled dystrophic axons and axonal retraction balls in and around acute ischemic lesions. The pattern of differential changes in immunoreactivity was essentially the same in all acute ischemic injuries, including both diffuse lesions in the CA1 field (Sommer's sector) and discrete infarcts in CA1 and neocortex. In addition, immunoreactivity for the immediate early gene product c-fos was enhanced in and around the acute ischemic lesions that we studied. In some very acute lesions, immunoreactivity for glial fibrillary acidic protein (GFAP) was depleted in areas of severe ischemia and necrosis, but, as expected, GFAP immunoreactivity was increased in lesions more than a few days old. In contrast, the loss of SMI-32 immunoreactivity persisted in chronic lesions. These findings are consistent with those of experimental ischemia in animals and confirm the relevance of these studies for human cerebral ischemia. The pattern of selective changes also resembles that of injuries induced directly by excitatory amino acids, which may play a significant role in the pathogenesis of ischemic damage.
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PMID:Immunohistochemical patterns of selective cellular vulnerability in human cerebral ischemia. 827 38

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

Changes in drebrin, MAP2 (postsynaptic marker) and synaptophysin (presynaptic marker) in rat brains were examined after 20 min of transient cerebral ischemia. Immunoreactivity for drebrin and MAP2 in hippocampus CA1 area decreased 7 days after ischemia. The immunoreactivity for debrin in stratum lucidum of hippocampus CA3 area increased 7 days after ischemia. Sodium dodecyl sulfate gel electrophoresis and immunoblot procedures using an antibody to drebrin, MAP2 and synaptophysin were carried out. The levels of drebrin and MAP2 in hippocampus decreased significantly 4 hours and 7 days after recirculation. In contrast, the level of synaptophysin was unchanged. The levels of each protein in cerebral cortex showed no significant changes. The changes after ischemia seemed to occur at the same time both in the dendritic spines and in their shafts, and the increase of the immunoreactivity for drebrin in CA3 might suggest the change of cytoskeletal protein synthesis in survived neurons.
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PMID:[The changes of central nervous synapses after transient cerebral ischemia]. 858 59


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