HEME OXYGENASE-1 (HO-1) PROTEIN INDUCTION IN RAT-BRAIN FOLLOWING FOCAL ISCHEMIA

The induction of the heme oxygenase-1 (HO-1) protein, also called HSP3 2, was compared to HSP70 heat shock protein induction following focal ischemia. Adult Sprague-Dawley male rats (n = 14) were subjected to ei ther 30 min or 2 h of focal cerebral ischemia using the suture, middle -cerebral-artery (MCA) occlusion model. Controls (n = 4) had sham surg ery. Following 24 h of reperfusion, subjects were killed and their bra ins stained immunocytochemically for HO-1 and the HSP70 heat shock pro teins. One day following 30 min of ischemia, HO-1 and HSP70 staining i n striatum occurred mainly in endothelial cells in infarcts and in gli al cells surrounding the areas of infarction. Following the 30 min isc hemia HO-1 was not induced in cortex whereas HSP70 was induced in cort ical neurons in the MCA distribution. One day following 2 h of MCA isc hemia, both HO-1 and HSP70 were induced in neurons in cortex in the MC A distribution. HO-1, however, was induced in glial cells throughout i psilateral cortex, inside as well as outside the MCA distribution. Thi s suggests that translation and/or transcription of the HO-1 and HSP70 genes are blocked in neurons and glia destined to die within infarcts , whereas translation of these stress genes continues in the endotheli al cells. The duration of ischemia required to induce HSP70 in cortica l neurons appears to be less than that required to induce HO-1 in cort ical glia. Prolonged spreading depression and/or diffuse hemispheric i schemia may induce HO-1 in glia throughout the ipsilateral cortex via immediate early gene activation of the AP-1 site in the HO-1 promoter. Since HO-1 degrades heme, a pro-oxidant, to antioxidant molecules, th e induction of HO-1 may augment oxidative defense mechanisms compromis ed by cerebral ischemia.