P Q-TYPE CA2+ CHANNEL BLOCKER OMEGA-AGATOXIN IVA PROTECTS AGAINST BRAIN INJURY AFTER FOCAL ISCHEMIA IN RATS/

Recently, P/Q-type Ca2+ channels have been shown to be involved in neu rotransmission in the central nervous system in mammals. We evaluated the effects of the P/Q-type Ca2+ channel blocker omega-agatoxin IVA (o mega-Aga-IVA) on brain edema formation and infarct size determined aft er 24 h of reperfusion following 1 h of middle cerebral artery (MCA) o cclusion in rats. Intracerebroventricular (i.c.v.) treatment with omeg a-Aga-IVA significantly attenuated the postischemic increase of brain water content. omega-Aga-IVA also significantly reduced the size of th e infarct area determined by triphenyltetrazolium chloride staining af ter 24 h of reperfusion. omega-Aga-IVA (30 pmol, i.c.v.), which exhibi ted a neuroprotective effect, had no significant effect on the magnitu de of intra-and postischemic brain temperature when compared with vehi cle-treated rats. This indicates that the postischemic neuroprotective effect of omega-Aga-IVA is produced by a direct and not an indirect e ffect via hypothermia. These results suggest that P/Q-type Ca2+ channe ls may be involved in the development of focal ischemic brain injury a nd that blockers of these channels may be therapeutically useful again st ischemic injury. (C) 1997 Elsevier Science B.V.