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

The tyrosine phosphorylation of microtubule-associated protein (MAP) kinase was examined in the gerbil brain after transient ischemia and reperfusion. Phosphorylation of MAP kinase was maximal within 1 min of reperfusion following 5 min of ischemia and returned to control levels as early as 5 min postischemia. The greatest increase in MAP kinase phosphorylation was detected in the hippocampus, with minor increases in other ischemic regions of the brain. Several tyrosine-phosphorylated proteins were detected in the gerbil hippocampus; however, the ischemia and reperfusion injury only increased tyrosine phosphorylation of MAP kinase. The increase in tyrosine phosphorylation was prevented by the N-methyl-D-aspartate (NMDA) receptor blocker (+)-MK-801, whereas a non-NMDA receptor blocker, 6-cyano-7-nitroquinoxaline-2,3-dione, was ineffective. Pretreatment of gerbils with calcium channel blockers also prevented the tyrosine phosphorylation of MAP kinase in the ischemic brain. Altogether, these results imply an involvement of glutamate receptors and calcium during the tyrosine phosphorylation of MAP kinase. Tyrosine phosphorylation was also prevented when ischemia and reperfusion were conducted under hypothermic conditions, which protect against neurodegenerative damage. These findings implicate a role for MAP kinase in neuronal damage resulting from ischemia and reperfusion.
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PMID:Tyrosine phosphorylation of microtubule-associated protein kinase after transient ischemia in the gerbil brain. 132 34

Differential vulnerability of the major components of microtubules was examined in ischemic gerbil brains by a light microscopic, immunohistochemical method using monoclonal antibodies for microtubule-associated protein (MAP) 1A and MAP2, polyclonal antibody for MAP1 and 2 as well as monoclonal antibody for alpha-tubulin. Progressive cerebral ischemia during unilateral carotid occlusion for 5, 15 and 120 min and reperfusion for 3, 12 and 48 h following bilateral carotid occlusion for 10 min were studied. Ischemic lesions in the subiculum-CA1 region were visualized by all antibodies after ischemia for 5 min but the antibody for alpha-tubulin was less sensitive. The antibody for alpha-tubulin was also less sensitive than antibodies for MAPs for detection of early postischemic lesions. Differential sensitivity was also observed in the cerebral cortex and other brain regions. Microtubules in myelinated axons were more stable than those in dendrites. The observed loss of immunohistochemical reactivities for MAPs and alpha-tubulin may have been caused by activation of calcium-dependent proteolytic enzymes such as calpains. The discrepancy between MAPs and alpha-tubulin could be due to differences in affinities or topographic distributions of these proteins within microtubules.
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PMID:Differential vulnerability of microtubule components in cerebral ischemia. 225 7

Previous studies in gerbils have shown that cytoskeletal disruption and a loss of the dendritic microtubule-associated protein, MAP2, may occur after short periods of transient global ischemia. tau, a predominantly axonal microtubule-associated protein, has not been examined following ischemia. We compared neuronal damage with alterations in MAP2, tau, and 72-kD heat shock protein (HSP72) immunostaining at various reperfusion times following 20 min of ischemia in the rat four-vessel occlusion model. tau accumulated in neuronal cell bodies throughout the hippocampal formation 30 min to 2 h after the ischemic insult. Perikaryal tau immunostaining was transient in most regions, but persisted in polymorphic hilar neurons. This was accompanied by a loss of immunostaining in the target of many hilar neurons, the inner molecular layer of the dentate gyrus. The same neuronal populations that exhibited increased tau immunostaining of perikarya later displayed an induction of HSP72 immunoreactivity. In contrast, loss of MAP2 immunostaining was not consistently observed before neuronal death and did not correspond to HSP72 induction. The altered tau immunostaining is not the direct result of excitotoxic insult, as intrahippocampal injection of kainic acid did not cause the somal accumulation of tau, but did cause disruption of MAP2 immunostaining. Taken together, the results suggest that the somal accumulation of tau is an early, sensitive, and selective marker of ischemic insult.
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PMID:Alterations in tau immunostaining in the rat hippocampus following transient cerebral ischemia. 751 35

The protective effects of a novel dihydropyridine calcium antagonist with platelet-activating factor-antagonistic action, F-0401, on ischemic brain damage were investigated using experimental ischemia models in rats and gerbils. F-0401 (1 and 10 mg/kg, i.p.) prevented increases in water content, determined by the wet-dry method, in ischemic areas 24 hr after 1 hr of middle cerebral artery occlusion in the rat. Pretreatment with F-0401 (1 and 10 mg/kg, i.p.) prevented extravasation of Evans blue dye in the brain following 2 hr of bilateral carotid artery occlusion and 2 hr of reperfusion in the rat. Pretreatment with F-0401 (1 and 10 mg/kg, i.p.) protected against neuronal damage to hippocampal CA1 pyramidal cells following 3 and 5 min of forebrain ischemia in the gerbil. Immunostaining against microtubule-associated protein-2 also demonstrated preservation of CA1 neurons in F-0401-treated animals. Thus, this study shows that F-0401 prevents the occurrence of brain edema, disruption of blood-brain barrier and neuronal damage caused by cerebral ischemia. The results demonstrate that F-0401 may be a powerful candidate as a therapeutic agent in the treatment of acute stroke in man.
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PMID:Protective effects of a novel calcium antagonist with platelet-activating factor-antagonistic action, F-0401, against ischemic brain damage. 784 11

The effect of naftidrofuryl, a drug used in ischemia for its vasodilator properties and its protective effect on neuronal survival, was investigated on the maturation of cultured chicken spinal cord neurons, focusing on the presence of proteins specific for the developing neuronal cytoskeleton. Although no influence of naftidrofuryl on the rate of growth of neurites was observed, the drug enhanced the relative amount of the high molecular weight neurofilament subunit without affecting the concentration of a microtubule-associated protein, MAP2. These findings suggest that the effect of naftidrofuryl on cultured spinal cord neurons might involve molecular events directly associated with the induction of a mature cytoskeleton architecture, instead of stimulating undifferentiated neurite growth.
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PMID:Naftidrofuryl, a putative activator of neuron survival, stimulates the expression of neurofilament heavy subunit in cultivated spinal cord neurons from chicken. 816 24

Protein tyrosine phosphorylation plays an important role in the regulation of neuronal function. We examined the effects of inhibition of tyrosine phosphorylation on ischemic neuronal damage in the CA1 region of the hippocampus. In the gerbil hippocampus, genistein and lavendustin A, tyrosine kinase inhibitors, were administered 30 min before initiation of 5-min ischemia and reperfusion. Both genistein and lavendustin A blocked tyrosine phosphorylation and prevented delayed neuronal death (DND). However, genistein, an inactive analogue of genistein, did not block DND. Genistein was dose-dependent in the inhibition of DND after ischemia and reperfusion. Administration of genistein 5 to 10 min after ischemia and reperfusion was ineffective in blocking DND in the CA1 region of the hippocampus. The tyrosine kinase inhibitors selectively blocked the phosphorylation of microtubule-associated protein (MAP)-2 kinase following ischemia and reperfusion injury. These results suggest that tyrosine phosphorylation in the ischemic brain is important for neuronal injury and that MAP-2 kinase may play a role in the onset of delayed neuronal death.
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PMID:Inhibition of tyrosine phosphorylation prevents delayed neuronal death following cerebral ischemia. 838 29

Post-ischemic treatment of di-Calciphor (16,16'-dimethyl-15- dehydroprostaglandin B1) significantly improves animal survival and prevents ischemia-induced neurodegeneration of vulnerable forebrain regions assessed with histochemical and biochemical techniques in gerbils. Neuronal degeneration seen by Cresyl violet staining and silver impregnation in the CA1 sector of the hippocampus and the dorso-lateral sector of the striatum was significantly reduced in animals treated with di-Calciphor. In addition, the early onset of selective degradation of calpain I substrates spectrin and microtubule-associated protein (MAP2) in these same vulnerable regions was prevented. The lack of adverse side effects may facilitate the potential therapeutic use of this drug in preventing neuronal damage caused by stroke.
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PMID:Neuroprotective activity of dimer of 16,16'-dimethyl-15-dehydroprostaglandin B1 (di-Calciphor) in cerebral ischemia. 846 94

We have studied amyloid precursor protein (APP) expression in rat brain following transient global ischemia. Ischemic damage 24 h after 30 min of four-vessel occlusion (4VO) was limited to the caudate nucleus; hippocampal pyramidal neurons appeared histologically normal by light microscopy. Consistent with ongoing neurodegeneration in the caudate nucleus, microtubule-associated protein-2 (MAP-2) levels assessed by immunoblots were significantly reduced in homogenates of caudate nucleus after 4VO. MAP-2 levels In the hippocampus were comparable to control values. In contrast, full length APP levels in both the caudate nucleus and hippocampal homogenates were significantly decreased following 4VO despite normal hippocampal morphology at 24 h. These findings suggest that decrements in full length APP precede overt neuronal damage and may play a role in the subsequent delayed neurodegeneration in the hippocampus.
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PMID:Decrease in amyloid precursor protein precedes hippocampal degeneration in rat brain following transient global ischemia. 849 67

Following 5 min in vitro ischemia, total protein synthesis is dramatically and persistently inhibited in neurons in the rat hippocampal slice. This model system was used to explore the responses of individual proteins to this irreversible insult. In vitro ischemia inhibited new protein synthesis of most proteins analyzed; however, the synthesis of a 68/70 kDa protein was substantially stimulated for the first hour after ischemia. By 3 hr postischemia, its synthesis rates were depressed to 60% of control rates. Although the total amounts of most proteins were not significantly depleted for the first few hours after ail ischemic episode, there were several notable exceptions. The levels of HSC73, a constitutively expressed member of the 70 kDa stress protein family, were reduced after in vitro ischemia. In addition, MAP-2 (microtubule-associated protein-2) and alpha-tubulin were depleted in the early hours after the insult, with MAP-2 exhibiting a detectable depletion earlier than tubulin. In contrast, the levels and distribution of a 68 kDa neurofilament protein localized to CA3 pyramidal neurons in the slice, apparently distinct from the band whose new synthesis was stimulated, were not affected by the 5 min in vitro ischemia insult. Thus, the responses of individual proteins to ischemia varied considerably, These individual responses could play an important role in the damage mechanism that is initiated in response to in vitro ischemia.
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PMID:Time course of protein changes following in vitro ischemia in the rat hippocampal slice. 897 69

We developed a mouse model of embolic focal cerebral ischemia, in which a fibrin-rich clot was placed at the origin of the middle cerebral artery (MCA) in C57BL/6J mice (n = 31) and B6C3 mice (n = 10). An additional three non-embolized C57BL/6J mice were used as a control. Embolus induction, cerebral vascular perfusion deficit, and consequent ischemic cell damage were confirmed by histopathology, immunohistochemistry, laser confocal microscopy, and regional cerebral blood flow (rCBF) measurements. Reduction in rCBF and cerebral infarct were not detected in the control animals. An embolus was found in all C57BL/6J and B6C3 mice at 24 hours after injection of a clot. Regional CBF in the ipsilateral parietal cortex decreased to 23% (P < 0.05) and 17% (P < 0.05) of preembolization levels immediately and persisted for at least 1 hour in C57BL/6J mice (n = 6) and in B6C3 mice (n = 3), respectively. A significant decrease of rCBF was accompanied by a corresponding reduction of plasma perfusion in the ipsilateral MCA territory. Neurons exhibited marked reduction in microtubule-associated protein-2 immunostaining coincident with the area of perfusion deficit. The percent infarct volume was 30.3% +/- 13.4% for C57BL/6J mice (n = 17), and 38.3% +/- 15.3% for B6C3 mice (n = 7) at 24 hours after embolization. This model of embolic ischemia is relevant to thromboembolic stroke in humans and may be useful to investigate embolic cerebral ischemia in the genetically altered mouse and for evaluation of antiembolic therapies.
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PMID:A mouse model of embolic focal cerebral ischemia. 934 33


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