Protective effects of focal ischemic preconditioning and HSP70 expression on middle cerebral artery occlusion in rats.
To systematically evaluate the importance of protein synthesis in ischemic preconditioning (PC)-induced ischemic tolerance (IT), temporary middle cerebral artery occlusion (MCAO) by Longa (20 min) was used for PC (ischemic precondioning). Twenty-four hours of reperfusion was allowed after PC and before permanent MCAO to establish ischemic tolerance (IT) to compare with non-PC (sham-operated) rats (n = 5 for each group). Infarct size and neurological deficits were measured 24 h after PMCAO. Samples of brain were taken for the determination of HSP70 expression by Western blot analysis. The effects of the protein synthesis inhibitor cycloheximide administered just before PC or administered long after PC but just before PMCAO on IT were also determined (n = 5 for each group). Our results showed that hemispheric infarct was significantly reduced (P < 0.01) only if PC was performed after 24 h, and PC significantly (P < 0.05) reduced neurological deficits (similar to reductions in infarct size). Cycloheximide eliminated ischemic PC-induced IT effects on bothbrain injury and neurological deficits if administered before PC but not if administered long after PC but before PMCAO. PC produced no brain injury but did increase HSP70 protein 24 h after PC. Cycloheximide eliminated that effect. The results suggest that PC is a powerful inducer of ischemic brain tolerance as reflected by the preservation of brain tissue and motor function. PC induces IT that is dependent on de novo protein synthesis.
Zhao
Jianhua
J
Department of Neurology, Union Hospital, Tongji Medical College, Huagzhong University of Science and Technology, Wuhan 430022, China.
Sun
Senggang
S
Chen
Xiaowu
X
D000818:Animals; D015153:Blotting, Western; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology*; D019194:Ischemic Preconditioning; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control
D018840:HSP70 Heat-Shock Proteins