title: The role of GTP binding proteins in ischemic brain damage: autoradiographic and histopathological study.
abstract: Cerebral ischemia produces perturbation of signal transduction systems in neurons. In order to estimate the contribution of guanine nucleotide-binding protein (G-protein) to hippocampal neuronal death, the effect of pertussis toxin (PTX) on the CA1 pyramidal cell damage after transient forebrain ischemia in rats was examined. PTX was administered 3 days before 20 min of transient forebrain ischemia. PTX injection into the CA1 subfield failed to alter the number of ischemic-damaged CA1 pyramidal cells. In contrast, ventricular PTX injection exacerbated CA1 pyramidal cell damage. We also studied postischemic alteration of GTP binding sites in the hippocampal formation using quantitative in vitro autoradiography. Autoradiographic imaging demonstrated predominant distribution of GTP binding sites in synaptic areas in the hippocampus. No significant change of GTP binding activity was observed in the hippocampus until 2 days after recirculation. Seven days after ischemia, when the CA1 pyramidal cells were depleted, the GTP binding sites of the strata oriens and radiatum in the CA1 subfield had reduced by 32% and 31%, respectively. In contrast, GTP binding in the CA3 subfield and the dentate gyrus remained unaltered throughout the reperfusion period. These results suggest that the amount of G-proteins as estimated by GTP binding remained unaltered in the hippocampus during the early recirculation period, when the CA1 pyramidal cells were morphologically intact, and that signal transduction pathways mediated by Gi and Go do not play a major role in delayed death of the CA1 pyramidal cells.
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Aoki
authors.forename: H
authors.initials: H
authors.lastname: Onodera
authors.forename: Y
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: T
authors.initials: T
authors.lastname: Yae
authors.forename: Z
authors.initials: Z
authors.lastname: Jian
authors.forename: K
authors.initials: K
authors.lastname: Kogure
mesh_terms: D000818:Animals; D001345:Autoradiography; D019204:GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009419:Nerve Tissue Proteins / Q000502:physiology*; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
chemical_list: D009419:Nerve Tissue Proteins; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins