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

Immunohistochemical changes of striatal interneurons in the gerbil were investigated 1 h-7 days after 10 min cerebral ischemia. Marked reduction of parvalbumin-immunoreactive interneurons was seen in the striatum from 24 h after ischemia. MAP2 (microtubule-associated protein 2) immunoreactivity markedly decreased in striatal neurons 5 h after ischemia but was unaffected in interneurons. Thereafter, a severe loss of MAP2 immunoreactivity in the interneurons was found 48 h and 7 days after ischemia. The results demonstrate that transient cerebral ischemia can cause a loss of parvalbumin and MAP2 immunoreactivity in interneurons in the dorsolateral striatum in a delayed fashion as compared with a rapid loss of striatal neurons.
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PMID:Delayed damage of striatal interneurons after cerebral ischemia in the gerbil. 797 Feb 28

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

Cerebral ischemia induces major neuronal morphological alterations. It is not clear, however, whether this is directly caused by O2 deprivation. To determine the effect of hypoxia on cytoskeletal structures and neuronal morphology, we performed experiments and examined anoxia-induced changes in microtubule-associated protein 2 (MAP2) and cell morphology in hippocampal slices in vitro. Anoxia (measured PO2 = 0 Torr) induced a marked loss in dendritic MAP2 immunoreactivity and cell swelling of hippocampal neurons by 2 h after O2 reinstitution. These changes were severe in CA1 and CA3 neurons and comparatively mild in dentate gyrus neurons. Quantitative analysis showed that 10 min of anoxia induced a 30% loss of MAP2-positive dendrites but this increased to 70% after 30 min of anoxia. A concurrent major increase in somata area of about 100% and 200% was observed in CA1 and CA3 neurons respectively. Somata area in the lower dentate gyrus, however, increased either insignificantly or by only 30% for the respective periods of anoxia. These results suggest that deprivation of O2 can by itself induce a major loss in dendritic MAP2 immunoreactivity and changes in cell morphology in hippocampal neurons. These alterations occur rapidly after hypoxia, and the severity of these changes is directly related to the duration of anoxia and brain region in the hippocampus.
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PMID:Acute anoxia-induced alterations in MAP2 immunoreactivity and neuronal morphology in rat hippocampus. 836 56

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

Calpain, a neutral protease activated by calcium, may promote microtubular proteolysis in ischemic brain. We tested this hypothesis in an animal model of focal cerebral ischemia without reperfusion. The earliest sign of tissue injury was observed after no more than 15 min of ischemia, with coiling of apical dendrites immunolabeled to show microtubule-associated protein 2 (MAP2). After 6 h of ischemia, MAP2 immunoreactivity was markedly diminished in the infarct zone. Quantitative Western analysis demonstrated that MAP2 was almost unmeasurable after 24 h of ischemia. An increase in calpain activity, shown by an antibody recognizing calpain-cleaved spectrin fragments, paralleled the loss of MAP2 immunostaining. Double-labeled immunofluorescent studies showed that intraneuronal calpain activity preceded evidence of MAP2 proteolysis. Perikaryal immunolabeling of tau protein became increasingly prominent between 1 and 6 h in neurons located within the transition zone between ischemic and unaffected tissue. Western blot experiments confirmed that dephosphorylation of tau protein occurred during 24 h of ischemia, but was not associated with significant loss of tau antigen. We conclude that focal cerebral ischemia is associated with early microtubular proteolysis caused by calpain.
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PMID:Microtubular proteolysis in focal cerebral ischemia. 889 91

Increased intracellular calcium and cytoskeletal damage play a crucial role in neuronal death following injury such as cerebral ischemia. The effect of brain temperature on early intracellular calcium increase and neuronal cytoskeletal damage following cerebral ischemia has not been rigorously investigated. In the current communication we evaluated calmodulin (CaM) and microtubule-associated protein 2 (MAP2) in the same brain section using a double labeling immunohistochemical technique, and obtained evidence that the brain temperature has a significant effect on the early calcium increase and cytoskeletal damage as well as the delayed neuronal death occurring in CA1 sector of the gerbil hippocampus after transient forebrain ischemia. In the normothermia (36.7 degrees C) group, CaM and MAP2 immunoreactivity were markedly decreased within 48 h after ischemia and thereafter dramatic neuronal death (grade 3) was seen in the CA1 sector at 7 days. Mild hypothermia (33.3 degrees C) significantly protected against all these changes, whereas cytoskeletal damage and delayed neuronal death were aggravated by mild hyperthermia (39.7 degrees C). We conclude that mild hypothermia protects the brain against transient forebrain ischemia by reducing early cytoskeletal damage and subsequent neuronal death.
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PMID:Effects of brain temperature on calmodulin and microtubule-associated protein 2 immunoreactivity in the gerbil hippocampus following transient forebrain ischemia. 906 42

Calpain (calcium-activated neutral protease) has been implicated as playing a role of neuronal injury in cerebral ischemia and excitotoxicity. Here we report that, in addition to extreme excitotoxic conditions [N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainate challenges], other neurotoxins such as maitotoxin, A23187, and okadaic acid also induce calpain activation, as detected by m-calpain autolytic fragmentation and nonerythroid alpha-spectrin breakdown. Under the same conditions, calmodulin-dependent protein kinase II-alpha (CaMPK-IIalpha) and neuronal nitric oxide synthase (nNOS) are both proteolytically cleaved by calpain. Such fragmentation can be reduced by calpain inhibitors (acetyl-Leu-Leu-Nle-CHO and PD151746). In vitro digestion of protein extract from cortical cultures with purified mu- and m-calpain produced fragmentation patterns for CaMPK-IIalpha and nNOS similar to those produced in situ. Also, several other calpain-sensitive calmodulin-binding proteins (plasma membrane calcium pump, microtubule-associated protein 2, and calcineurin A) and protein kinase C-alpha are also degraded in neurotoxin-treated cultures. Lastly, in a rat pup model of acute excitotoxicity, intrastriatal injection of NMDA resulted in breakdown of CaMPK-IIalpha and nNOS. The degradation of CaMPK-IIalpha, nNOS, and other endogenous calpain substrates may contribute to the neuronal injury associated with various neurotoxins.
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PMID:Neuronal nitric oxide synthase and calmodulin-dependent protein kinase IIalpha undergo neurotoxin-induced proteolysis. 928 22

We investigated the expression of cyclin D1 and its kinase, cdk4, after induction of focal cerebral ischemia in the rat. Brain from rats (n = 6) subjected to 2 hours of transient middle cerebral artery occlusion and 46 hours of reperfusion, and control sham-operated (n = 3) and normal (n = 2) rats were processed for dual label immunohistochemical study for cellular identification of the expression of these cell cycle proteins. Antibodies raised against microtubule-associated protein 2 and neuronal specific enolase for neurons, glial fibrillary acidic protein for astrocytes, myelin basic protein for oligodendrocytes and lectin histochemical study with the B4-isolectin for microglia were used for cell type identification. Double staining for DNA fragmentation detection (TUNEL) and expression of cyclin D1 and cdk4 also was performed. Cyclin D1 and cdk4 were selectively expressed in morphologically intact or altered neurons and oligodendrocytes localized to the ischemic tissue. Apoptotic cells were not immunoreactive to cyclin D1 and cdk4 at 46 hours after 2 hours of middle cerebral artery occlusion. The selective expression of cell cycle proteins observed in nonapoptotic ischemic postmitotic neurons and oligodendrocytes suggests a role for these proteins in cell survival after transient focal cerebral ischemia.
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PMID:Immunoreactivity of cyclin D1/cdk4 in neurons and oligodendrocytes after focal cerebral ischemia in rat. 929 May 82

Recently, attention has been focused on the degradation of cytoskeletal proteins in animal models of cerebral ischemia, as the collapse of cytoskeletal proteins may be closely related to cytoskeletal disintegration and ultimate neuronal cell death. Among these proteins, microtubule-associated protein 2 (MAP2) has been shown to be highly vulnerable to ischemic injuries. To determine the degree of anesthetic effect on the collapse of cytoskeletal proteins, we compared the effect of three inhalation anesthetics; isoflurane, halothane, and nitrous oxide (N2O), on MAP2 degradation during 20 min of forebrain ischemia in the rat. Under equipotent anesthesia, forebrain ischemia was induced by the occlusion of the bilateral common carotid artery (CCA) combined with a lowering of mean arterial pressure (mAP) to 50 mmHg. After 20 min of ischemia, three regions of the brain, the frontoparietal cortex, brainstem, and hippocampus, were removed and separately homogenized. Subsequently, MAP2 of each region was measured using an enzyme-linked immunosorbent assay (ELISA). In the frontoparietal cortex and hippocampus, MAP2 was significantly protected from degradation when isoflurane was used combined with nitrogen (N2). However, the protective effects of isoflurane were drastically reduced when N2O was given instead of N2. These results suggest that the use of N2O should be discontinued when severe cerebral ischemia is accidentally incurred during anesthetic management.
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PMID:Nitrous oxide attenuates the protective effect of isoflurane on microtubule-associated protein2 degradation during forebrain ischemia in the rat. 932 46


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