[Induction of HSP70 and neuronal damage following transient cerebral ischemia in rats].
Various studies have demonstrated increased synthesis of heat shock protein 70 (HSP70) in brain following transient ischemia, and a protective role for HSP70 against ischemic insult has been hypothesized. In this study, we determined the time course of HSP70 mRNA and HSP70 induction in rat hippocampus following ischemia using Pulsinelli's four-vessel occlusion model, and suggested a protective role for HSP70 induction in limiting ischemic damage to neurons and delayed neuronal death. In Northern blotting analysis using human HSP70 DNA (pH 2.3) as a probe, the accumulation of HSP70 mRNA became evident at 4 h, and continued until 16 h, after 5 min ischemia, while it appeared at 2 h, and continued above control level until 24 h, after 30 min ischemia. In immunoblot analysis using anti-HSP70 antibody, induction of HSP70 appeared 24 h and reached a maximum level 48 h after 5 min ischemia. In immunohistochemical analysis using anti-HSP70 antibody, no staining was detected until 16 h after 5 min ischemia but staining in CA1 gradually increased from 1 day after ischemia and reached a maximum level 2 days after ischemia. Similar time profiles in staining pattern of HSP70 were observed in CA3 and CA4 neuronal cells following 30 min ischemia. Rats pretreated with 5 min ischemia (nonlethal for CA1 pyramidal neurons) were exposed to a 30 min, lethal period of ischemia, 2 days after pretreatment, at which time considerable staining of HSP70 was present. Pretreated rats had much neuronal damage in the CA1 sector less than did rats subjected to lethal, 30 min ischemia alone. These results suggest that neurons in rat hippocampus become tolerant to lethal treatment due to expression of the HSP70 gene and HSP70 protein synthesis induced by mild ischemic pretreatment.
Nishi
S
S
Department of Neurosurgery, Faculty of Medicine, Kyoto University, Japan.
D000818:Animals; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D006360:Heat-Shock Proteins; D012333:RNA, Messenger