Regional expression of heat shock protein-70 mRNA and c-fos mRNA following focal ischemia in rat brain.
In situ hybridization was used to estimate regional levels of heat shock protein-70 (HSP-70) mRNA and c-fos mRNA in two related models of focal cerebral ischemia. In the first model, permanent occlusion of the distal middle cerebral artery (MCA) alone caused a patchy increase in HSP-70 mRNA by 1 h in the central zone of the MCA territory of the ipsilateral neocortex. Tissue levels of HSP-70 mRNA continued to increase for several hours and remained elevated at 24 h. In contrast to the focal expression of HSP-70, c-fos mRNA was increased throughout the ipsilateral cerebral cortex by 15 min and remained elevated for least 3 h. The wide distribution of c-fos expression suggests it may have been caused by spreading depression. In the second model, severe focal ischemia was produced with a combination of transient (1-h) bilateral carotid artery occlusion and permanent MCA occlusion. Combined occlusion for 1 h without reperfusion caused expression of HSP-70 mRNA only in regions adjacent to the central zone of the MCA territory of the neocortex. However, reperfusion of the carotids for 2 h generated intense expression of HSP-70 mRNA throughout most of the ipsilateral cerebral cortex, white matter, striatum, and hippocampus. The wide-spread increase in HSP-70 mRNA suggests that reperfusion triggered expression in all previously ischemic regions. However, at 24 h of reperfusion, increased levels of HSP-70 mRNA were restricted primarily to the ischemic core of the neocortex. These results suggest that expression of HSP-70 mRNA is prolonged in regions undergoing injury, but is transient in surrounding regions that recover.
Welsh
F A
FA
Division of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia.
Moyer
D J
DJ
Harris
V A
VA
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002339:Carotid Arteries / Q000601:surgery; D002536:Cerebral Arteries / Q000601:surgery; D015870:Gene Expression; D016762:Genes, fos; D006360:Heat-Shock Proteins / Q000235:genetics*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D006360:Heat-Shock Proteins; D012333:RNA, Messenger