Ebselen lowers plasma interleukin-6 levels and glial heme oxygenase-1 expression after focal photothrombotic brain ischemia

Heme oxygenase-1, an inducible heat shock protein, is upregulated by oxidat ive stress, and its expression is modulated by proinflammatory cytokines su ch as IL-1 and IL-6. In the present study, we investigated the effects of p ostlesional, orally applied ebselen, a neuroprotective antioxidant, on seru m levels of IL-6 and cerebral heme oxygenase-l expression following focal i schemia induced by photothrombosis. Ebselen (50 mg/kg body weight) was give n 30 min postlesion to male Wister rats. Animals were divided into four gro ups: sham-operated vehicle control (n = 9), sham-operated ebselen control ( n = 8), lesioned vehicle control (n = 14), and lesioned ebselen-treated (n = 17). Ebselen treatment resulted in a significant lowering of IL-6 plasma levels (26 +/- 5 pg/ml) as compared with that seen in lesioned vehicle cont rols (48 +/- 9 pg/ml) at 24 h postlesion. In sham-operated rats IL-6 was no t detectable, Heme oxygenase-1-positive glial cells were quantitated within topographically determined perilesional brain regions. Within the 0.5-mm-w ide rim region directly associated with the lesion core, no differences in the amount of heme oxygenase-1 positive glial cells were found. However, in the more remote ipsilateral perilesional cortex, significantly fewer heme oxygenase-1-positive glial cells were present within the supragranular cort ical layers of lesioned ebselen-treated rats compared to lesioned vehicle c ontrols (P < 0.001), In sham-operated rats, no glial heme oxygenase-1 induc tion occurred. The results indicate that postlesional ebselen treatment low ered plasma IL-6 levels subsequent to a photothrombotic lesion concomitant with a lowering of the heme oxygenase-1 response in glial cells. (C) 2000 A cademic Press.