ANIRACETAM, A PYRROLIDINONE-TYPE COGNITION ENHANCER, ATTENUATES THE HYDROXYL FREE-RADICAL FORMATION IN THE BRAIN OF MICE WITH BRAIN ISCHEMIA

We demonstrate here that aniracetam has the ability to block the forma tion of cytotoxic hydroxyl radicals (. OH) during ischaemia-reperfusio n of mouse brain. The fact that brain ischaemia for 40 min followed by reperfusion increased . OH was evidenced by detection of a peaked inc rease at 20 min after an ischaemic insult in the formation of 2,3-dihy droxy-benzoate (DHBA) from salicylate in cerebroventricular perfusate, a means of monitoring OH formation. A clearcut increase in dopamine w as also observed during and after brain ischaemia. The ischaemia-reper fusion mice given aniracetam at an intraperitoneal dose of 30 or 100 m gkg(-1) showed a smaller increase in the formation of DHBA than those given the vehicle only. Aniracetam at 100 mgkg(-1) significantly suppr essed the formation of DHBA by approximately 80%, becoming evident at 20 min after reperfusion and thereafter. Protection against death in m ice insulted with a 40-min brain ischaemia (3/13 vs 13/25) was observe d following 100 mgkg(-1) aniracetam. The increase in the dopamine leve ls was substantially reduced following aniracetam treatment and the re duction became significant at 20 min after reperfusion and thereafter in parallel with attenuation by aniracetam of DHBA formation. This fin ding suggests that the inhibitory activity of aniracetam in attenuatin g the hydroxyl free-radical formation in ischaemic mice is probably du e, at least in part, to its palliative action on the dopaminergic neur ons.