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)

Cerebral ischemia induces a massive efflux of glutamate causing delayed neuronal death in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats (WKY). It is obvious that L-N-nitroarginine (L-NNA; NO synthase (NOS) inhibitor), benzamide (poly(ADP-ribose) synthetase inhibitor), and growth factors are involved in reducing neuronal cell death due to toxic conditions, especially phosphatidylinositol 3 (PI3)-kinase activity; however, no studies have clarified whether genetic vulnerability to neurotoxic states is present in cortical neurons isolated from SHRSP. For this purpose, we prepared cortical neurons from WKY and SHRSP (15 weeks of gestation) to test the genetic vulnerability involved in the pathogenesis of stroke as well as apoptosis of cortical neurons isolated from SHRSP. We also examined the mechanisms necessary to reduce apoptosis under neurotoxic states using ultrastructural and biochemical techniques. Cortical neurons from SHRSP were in fact found to be more vulnerable than neurons from WKY and resulted in apoptosis when treated with nitric oxide (NO)- and N-methyl-D-aspartate (NMDA)-mediated neurotoxic agents. Growth factors, especially insulin-like growth factor (IGF), rescued neurons from NO- and NMDA-mediated neurotoxicity, particularly those from SHRSP. Conversely, benzamide and L-NNA reduced NMDA-mediated neurotoxicity but not NO-mediated toxicity. The ability to protect neurons from neurotoxicity was as follows: IGF-->nerve growth factor epidermal growth factor-->L-NNA-->benzamide. In addition, it was demonstrated that wortmannin, a PI3-kinase inhibitor, lessened the protective effects of these growth factors against NO-mediated toxicity. The data thus indicate that genetic factors related to neuronal vulnerability to apoptosis are involved in the pathogenesis of stroke lesions in SHRSP. PI3-kinase activity, which is stimulated by growth factors, is closely related to protective effects against NO- and NMDA-mediated toxicity in cortical neurons, especially those isolated from SHRSP. Moreover, the genetic vulnerability observed in SHRSP neurons is possibly linked to the inadequate activation of signaling pathways in the downstream of protein tyrosine kinases.
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PMID:Insulin-like growth factors prevent apoptosis in cortical neurons isolated from stroke-prone spontaneously hypertensive rats. 916 79

There is evidence that the excessive generation of reactive-oxygen radicals contributes to the brain injury associated with transient, cerebral ischemia. This study investigates the effects of tempol, a small, water-soluble molecule, that crosses biological membranes, on the brain injury caused by bilateral occlusion and reperfusion of both common carotid arteries in the gerbil (BCO). Treatment of gerbils with tempol (30 mg/kg i.p. at 30 min prior to reperfusion and at 1 and 6 h after the onset of reperfusion) reduced the formation of post-ischemic brain oedema. Tempol also attenuated the increase in the cerebral levels of malondialdehyde (MDA) and the hippocampal levels of myeloperoxidase (MPO) caused by cerebral ischemia and reperfusion. The immunohistochemical analysis of the hippocampal region of brains subjected to ischemia-reperfusion exhibited positive staining for nitrotyrosine (an indicator of the generation of peroxynitrite) and poly(ADP-ribose) synthetase (PARS) (an indicator of the activation of this nuclear enzyme secondary to single strand breaks in DNA). In gerbils subjected to BCO, which were treated with tempol, the degree of staining for nitrotyrosine and PARS was markedly reduced. Tempol increased survival and reduced the hyperactivity (secondary to the ischemia-induced neurodegeneration) caused by cerebral ischemia and reperfusion. The loss of neurons from the pyramidal layer of the CA1 region caused by ischemia and reperfusion was also attenuated by treatment of gerbils with tempol. This is the first evidence that the membrane-permeable, radical scavenger tempol reduces the cerebral injury caused by transient, cerebral ischemia in vivo.
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PMID:Effects of tempol, a membrane-permeable radical scavenger, in a gerbil model of brain injury. 1096 3