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

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

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

One of the most prominent features of the early phase of cerebral ischaemia is the immunohistochemical collapse of cytoskeletal proteins. Among these proteins, microtubule-associated protein 2 (MtP2) has been shown to be vulnerable to ischaemic injuries. In order to identify a suitable volatile anaesthetic on the basis of cytoskeletal protein breakdown during cerebral ischaemia, we have compared the effects of isoflurane and halothane on MtP2 degradation in rats. Under equipotent isoflurane or halothane anaesthesia, forebrain ischaemia was induced by occlusion of the bilateral common carotid artery, combined with a decrease in mean arterial pressure to 50 mm Hg. After 20 min of ischaemia, the frontoparietal cortex, brainstem, hippocampus and cerebellum were removed separately and homogenized. MtP2 from each region was measured using an enzyme-linked immunosorbent assay. MtP2 degradation in the frontoparietal cortex and hippocampus was significantly (P < 0.05 and P < 0.01) less with isoflurane anaesthesia (75.6 (SD 10.7)% and 72.3 (12.8)%, respectively) than with halothane (65.0 (13.1)% and 54.7 (13.9)%, respectively).
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PMID:Isoflurane reduces microtubule-associated protein 2 degradation compared with halothane during forebrain ischaemia in the rat. 812 1

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

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

Using a silver impregnation (argyrophil III) and immunohistochemistry, acute cytopathic features after cerebral ischemia were investigated. Additionally, functional recovery and interconnection between the host and graft was also explored after neural graft. Animals were embolized in unilateral middle cerebral artery for 1 h. Argyrophil III method demonstrated "collapsed" dark neurons in the striatum, cortex, reticular thalamus, amygdala, and hypothalamus on ischemic side. These neurons exhibited characteristic shrunken somata with corkscrew-like dendrites, suggesting changes in cytoskeletal protein. In the above mentioned areas, the loss of immunoreactivity for mu-calpain proenzyme and microtubule-associated protein 2 was also detected. Neural graft into the ischemic striatum was made 2 weeks after the ischemia paradign. The grafted striatal cells were prepared from E15 fetuses to make cell suspension marked by rhodamine-labeled latex microspheres. Methamphetamine-evoked rotations were detected after ischemia. These motor alterations were reduced gradually but significantly at 8 weeks after the graft. Interconnecton between the host and grafted cells was then studied in a brain slice preparation after loading fura-2 AM. About 10% of grafted cells tested from rats that showed motor amelioration exhibited [Ca2+]i increase to the electrical stimulation applied to the neighboring host tissue. Data indicate that, in the very early stage after ischemia, cytoskeletal damages, especially on microtubules, started and this would lead to later infarct. The graft survived in the ischemic striatum having connections with the host, and this might be partly involved in the amelioration of motor function.
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PMID:Early cytopathic features in rat ischemia model and reconstruction by neural graft. 863 48

Axonal injury following cerebral ischaemia has attracted less attention than damage in grey matter. However, it is becoming increasingly recognised that axons are highly vulnerable to focal ischaemia [D. Dewar, D.A. Dawson, Changes of cytoskeletal protein immunostaining in myelinated fibre tracts after focal cerebral ischaemia in the rat, Acta. Neuropathol., 93 (1997) 71-77] [2]; [L. Pantoni, J.H. Garcia, J.A. Gutierrez, Cerebral white matter is highly vulnerable to ischemia, Stroke, 27 (1996) 1641-1647] [10]; [P. S. Yam, T. Takasago, D. Dewar, D.I. Graham, J. McCulloch, Amyloid precursor protein accumulates in white matter at the margin of a focal ischaemic lesion, Brain Res., 760 (1997) 150-157] [15]. Since white matter does not contain neuronal cell bodies or synapses it is likely that the mechanisms of injury and strategies for its protection are different from those in grey matter. In order that the effect of therapeutic intervention on the protection of axons can be assessed, a method by which axonal injury can be mapped and quantified is required. For this purpose, we investigated immunocytochemical methods using amyloid precursor protein (APP) following permanent middle cerebral artery occlusion in the rat. APP is transported by fast anterograde axonal transport [E.H. Koo, S.S. Sisodia, D.R. Archer, L.J. Martin, A. Weidemann, K. Beyreuther, P. Fischer, C.L. Masters, D.L. Price, Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport, Proc. Natl. Acad. Sci. U.S.A. 87 (1990) 1561-1565] [7] and has been shown to accumulate following a variety of insults to axons, indicative of dysfunction of axonal transport [R.N. Kalaria, S.U. Bhatti, E.A. Palatinsky, D.H. Pennington, E.R. Shelton, H.W. Chan, G. Perry, W.D. Lust, Accumulation of the beta amyloid precursor protein at sites of ischemic injury in rat brain, Neuroreport, 4 (1993) 211-214] [4]; [T. Kawarabayashi, M. Shoji, Y. Harigaya, H. Yamaguchi, S. Hirai, Expression of APP in the early stage of brain damage, Brain Res., 563 (1991) 334-338] [5]; [N. Otsuka, M. Tomonaga, K. Ikeda, Rapid appearance of beta-amyloid precursor protein immunoreactivity in damaged axons and reactive glial cells in rat brain following needle stab injury, Brain Res., 568 (1991) 335-338] [9]; [K. Shigematsu, P. L. McGeer, Accumulation of amyloid precursor protein in neurons after intraventricular injection of colchicine, Am. J. Pathol., 140 (1992) 787-794] [12]. We have been able to map the topographical relationship between APP accumulation and region of infarction using immunocytochemistry and image analysis techniques. Additionally, using a semi-quantitative scoring system, we have demonstrated that there is a relationship between the amount of APP accumulation and the volume of infarction following middle cerebral artery occlusion. These methods will be useful in the future for the assessment of therapeutic interventions on the protection of axons following ischaemic injury.
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PMID:Topographical and quantitative assessment of white matter injury following a focal ischaemic lesion in the rat brain. 963 Jul

Although stroke in humans usually afflicts the elderly, most experimental studies on the nature of cerebral ischemia have used young animals. This is especially important when studying restorative processes that are age dependent. To explore the potential of older animals to initiate regenerative processes after cerebral ischemia, the authors studied the expression of the juvenile-specific cytoskeletal protein, microtubule-associated protein (MAP) 1B, and the adult-specific protein, MAP2, in male Sprague-Dawley rats at 3 months and 20 months of age. The levels of MAP1B and MAP2 transcripts and the corresponding proteins declined with increasing age in the hippocampus. In the cortex, the levels of the transcripts did not change significantly with age, but the morphologic features of immunostained fibers were clearly affected by age; that is, cortical MAP1B fibers became thicker, and MAP2 fibers, more diffuse, in aged rats. Focal cerebral ischemia, produced by reversible occlusion of the right middle cerebral artery, resulted in a large decrease in the expression of both MAP1B and MAP2 in the infarct core at the messenger ribonucleic acid and protein levels. However, at 1 week after the stroke, there was vigorous expression of MAP1B and its messenger ribonucleic acid, as well as MAP2 protein, in the border zone adjacent to the infarct of 3-month-old and 20 month-old male Sprague-Dawley rats. The upregulation of these key cytologic elements generally was diminished in aged rats compared with young animals, although the morphologic features of fibers in the infarct border zone were similar in both age groups. These results suggest that the regenerative potential of the aged rat brain appears to be competent, although attenuated, at least with respect to MAP1B and MAP2 expression up to 20 months of age.
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PMID:Upregulation of MAP1B and MAP2 in the rat brain after middle cerebral artery occlusion: effect of age. 1019 12

The pathogenesis of cerebral ischemia/reperfusion (I/R) involves cytokine/chemokine production, inflammatory cell influx, astrogliosis, cytoskeletal protein degradation and breakdown of the blood-brain barrier. (-)-Naloxone is able to reduce infarct volume and has been used as a therapeutic agent for cerebral I/R injuries. However, its effects on the mentioned pathophysiologic changes have scarcely been addressed. Cerebral I/R was produced by occluding and opening bilateral common carotid artery and unilateral middle cerebral artery in Sprague-Dawley rats. After cerebral I/R, the degradation of neuronal microtubule-associated protein-2 (MAP-2) was strongly associated with astrogliosis, inflammatory cell infiltration, cytokine/chemokine overproduction, and matrix metalloproteinase-9 activation. (-)-Naloxone pretreatment suppresses post-ischemic activation and preserves more MAP-2 protein. Therefore, (-)-naloxone administration might be an effective therapeutic intervention for reducing ischemic injuries.
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PMID:Cerebral ischemia/reperfusion injury in rat brain: effects of naloxone. 1133

In the present study, we evaluated the time-course of caspase-3 activation, and the evolution of cell death following focal cerebral ischemia produced by transient middle cerebral artery occlusion in rats. Ischemia-induced active caspase-3 immunoreactivity in the striatum but not the cortex at 3 and 6 h time points post-reperfusion. Furthermore, using a novel approach to visualize enzymatic activity, deltaC-APP, a C-terminal cleavage product of APP generated by caspase-3, was found to immunolocalize to the same areas as active caspase-3. Double-labeling studies demonstrated co-localization of these two proteins at the cellular level. Further double-labeling experiments revealed that active caspase-3 was confined to neuronal cells which were still viable and thus immunoreactive for NeuN. DNA fragmentation, assessed histologically by terminal dUTP nick-end labeling (TUNEL), was observed in a small number of cells in the striatum as early as 3 h, but only began to appear in the cortex by 6 h. DNA fragmentation was progressive, and by 24 h post-reperfusion, large portions of both the striatum and cortex showed TUNEL positive cells. However, double-labeling of active caspase-3 with TUNEL showed only minimal co-localization at all time-points. Thus, caspase-3 activation is an event that appears to occur prior to DNA fragmentation. As a confirmation of the histological TUNEL data, 24 h ischemia also induced the generation of nucleosome fragments, evidenced by cell death enzyme-linked immunosorbent assay. Using a novel ischemia-induced substrate cleavage biochemical approach, spectrin P120 fragment, a caspase-specific cleavage product of alpha II spectrin, a cytoskeletal protein, was shown to be elevated by western blotting. Brain concentrations of both nucleosomes and spectrin P120 correlate with the degree of injury previously assessed by triphenyltetrazolium chloride staining and infarct volume calculation. Together, our findings suggest a possible association between caspase-3 activation and ischemic cell death following middle cerebral artery occlusion brain injury.
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PMID:Immunohistochemical and biochemical assessment of caspase-3 activation and DNA fragmentation following transient focal ischemia in the rat. 1240 27


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