title: Immunohistochemical study on distribution of NF-kappaB and p53 in gerbil hippocampus after transient cerebral ischemia: effect of pitavastatin.
abstract: We investigated the immunohistochemical alterations of the transcription nuclear factor kappa-B (NF-kappaB) and transcription factor p53 in the hippocampus after transient cerebral ischemia in gerbils. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin against the alterations of NF-kappaB, p53 and neuronal nuclei in the hippocampus after ischemia. Severe neuronal damage was observed in the hippocampal CA1 neurons 5 and 14 days after ischemia. In the present study, the increase of NF-kappaB immunoreactivity in glial cells and p53 immunoreactivity in neurons preceded neuronal damage in the hippocampal CA1 sector after ischemia. Thereafter, NF-kappaB immunoreactivity was induced highly in reactive astrocytes and microglia of the hippocampal CA1 sector where severe neuronal damage was observed. Our immunohistochemical study showed that pitavastatin prevented the alterations of NF-kappaB and p53 in the hippocampal CA1 sector 5 days after transient ischemia. Furthermore, our results with neuronal nuclei immunostaining indicate that pitavastatin dose-dependently prevented the neuronal cell death in the hippocampal CA1 sector 5 days after transient cerebral ischemia. These results suggest that the up-regulations of NF-kappaB in glia and p53 in neurons can cause neuronal cell death after ischemia. Our findings also support the hypothesis that NF-kappaB- and/or p53-mediated neuronal cell death is prevented through decreasing oxidative stress by pitavastatin. Thus, NF-kappaB and p53 may provide an attractive target for the development of novel therapeutic approaches for brain stroke.
authors.affiliation: Department of Drug Metabolism and Therapeutics, Graduate School and Faculty of Pharmaceutical Sciences, The University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tounai
authors.forename: Natsumi
authors.initials: N
authors.lastname: Hayakawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Araki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011804:Quinolines / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D011804:Quinolines; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; C108475:pitavastatin