Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During and after middle cerebral artery occlusion in mice, CaMKII alpha protein was irreversibly translocated from the soluble to the Triton X-100-nonsoluble fraction. This decrease in solubility had a strong effect on activity: CaMKII alpha was almost completely inactivated after being translocated. Results from solubilization experiments suggest that different mechanisms underlie the conversion of CaMKII alpha protein from a soluble to a detergent nonsoluble form in ischemic as opposite to nonischemic tissue. Analysis of the phosphorylation state of CaMKII alpha revealed that in the total homogenate and the Triton X-100-nonsoluble fraction, CaMKII alpha phosphorylated at only one site was the dominant phosphorylated form, whereas in the soluble fraction CaMKII phosphorylated at two sites was the predominant phosphorylated species. Investigation of the mechanisms underlying ischemia-induced changes in the solubility of CaMKII alpha could help to elucidate processes triggered by transient focal cerebral ischemia that lead to neuronal cell injury.
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PMID:Phosphorylation state, solubility, and activity of calcium/calmodulin-dependent protein kinase II alpha in transient focal ischemia in mouse brain. 1219 52

Neuronal repair following injury requires recruitment of large amounts of membranous proteins into synaptic and other cell membranes, which is carried out by the fusion of transport vesicles to their target membranes. A critical molecule responsible for assemblage of membranous proteins is N-ethylmaleimide-sensitive factor (NSF) which is an ATPase. To study whether NSF is involved in ischemic neurological deficits and delayed neuronal death, we investigated alterations of NSF after transient cerebral ischemia by means of biochemical methods, as well as confocal and electron microscopy. We found that transient cerebral ischemia induced depletion of free NSF and concomitantly relocalization of NSF into the Triton X-100-insoluble fraction including postsynaptic densities in CA1 neurons during the postischemic period. The NSF alterations are accompanied by accumulation of large quantities of intracellular vesicles in CA1 neurons that are undergoing delayed neuronal death after transient cerebral ischemia. Therefore, permanent depletion of free NSF and relocalization of NSF into the Triton X-100-insoluble fraction may disable the vesicle fusion machinery necessary for repair of synaptic injury, and ultimately leads to synaptic dysfunction and delayed neuronal death in CA1 neurons after transient cerebral ischemia.
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PMID:Alterations of N-ethylmaleimide-sensitive atpase following transient cerebral ischemia. 1546 84

Membrane rafts, rich in sphingolipids and cholesterol, are membrane microdomains important in neuronal domain-specific signaling events such as during axonal outgrowth and neuronal death. The present study seeks to determine the spatiotemporal association of several axonal guidance signaling molecules with membrane rafts. These molecules are Neuropilin-1 (NRP-1), Fer Kinase, and collapsin response mediator proteins (CRMPs), which are known to have important functions in axonal outgrowth and neuronal death caused by cerebral ischemia. Mice were subjected to sham or a 1h unilateral middle cerebral artery occlusion (MCAO) followed by a time course of reperfusion up to 24h. Brain cortices were separated and membrane rafts were extracted based on their insolubility in Triton X-100 and separation by sucrose gradient fractionation. We demonstrate the early and transient induction of NRP-1 and CRMP-2 in membrane rafts in both ipsilateral and contralateral hemispheres, in contrast to an early, but sustained elevation of Fer kinase and other CRMPs (1, 3, 4, 5) in response to unilateral MCAO. The fact that NRP1/Fer kinase/CRMP-2 co-localize in membrane rafts early during ischemic injury suggests that the membrane rafts may form a scaffold to support and initiate NRP1/Fer/CRMP-2-mediated signal transduction in neuronal damage response during ischemia-reperfusion. Further understanding of the time-specific and membrane domain-specific protein-protein interaction may lead to the identification of therapeutic targets for stroke.
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PMID:Transient and bilateral increase in Neuropilin-1, Fer kinase and collapsin response mediator proteins within membrane rafts following unilateral occlusion of the middle cerebral artery in mouse. 2049 26

Poloxamer 188 (P188), a multiblock copolymer surfactant, has been shown to protect against ischemic tissue injury of cardiac muscle, testes and skeletal muscle, but the mechanisms have not been fully understood. In this study, we explored whether P188 had a protective effect against cerebral ischemia/reperfusion injury and its underlying mechanisms. The in vivo results showed that P188 significantly reduced the infarct volume, ameliorated the brain edema and neurological symptoms 24 h after ischemia/reperfusion. In the long-term outcome study, P188 markedly alleviated brain atrophy and motor impairments and increased survival rate in 3 weeks of post stroke period. Additionally, P188 protected cultured hippucampal HT22 cells against oxygen-glucose deprivation and reoxygenation (OGD/R) injury. The ability in membrane sealing was assessed with two fluorescent membrane-impermeant dyes. The results showed that P188 treatment significantly reduced the PI-positive cells following ischemia/reperfusion injury and repaired the HT22 cell membrane rupture induced by Triton X-100. In addition, P188 inhibited ischemia/reperfusion-induced activation of matrix metalloproteinase (MMP)-9 and leakage of Evans blue. Therefore, the present study concludes that P188 can protect against cerebral ischemia/reperfusion injury, and the protection involves multi-mechanisms in addition to the membrane resealing.
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PMID:Poloxamer 188 protects neurons against ischemia/reperfusion injury through preserving integrity of cell membranes and blood brain barrier. 2361 90