Production of leukotrienes in a model of focal cerebral ischaemia in the rat

The aim of this work was to evaluate the role of leukotrienes in brain damage in vivoin a model of focal cerebral ischaemia in the rat, obtained by permanent occlusion of middle cerebral artery.A significant (P<0.01) elevation of LTC4, LTD4and LTE4(cysteinyl‐leukotrienes) levels occurred 4 h after ischaemia induction in the ipsilateral cortices of ischaemic compared to sham‐operated animals (3998±475 and 897±170 fmol g−1tissue, respectively, P<0.01).The NMDA receptor antagonist MK‐801 and the adenosine A2Areceptor antagonist SCH 58261 were administered in vivoat doses known to reduce infarct size and compared with the leukotriene biosynthesis inhibitor MK‐886.MK‐886 (0.3 and 2 mg kg−1i.v.) and MK‐801 (3 mg kg−1i.p.) decreased cysteinyl‐leukotriene levels (−78%, P<0.05; −100%, P<0.01; −92%, P<0.01, respectively) 4 h after permanent occlusion of the middle cerebral artery, whereas SCH 58261 (0.01 mg kg−1i.v.) had no significant effects.MK‐886 (2 mg kg−1i.v.) was also able to significantly reduce the cortical infarct size by 30% (P<0.05).We conclude that cysteinyl‐leukotriene formation is associated with NMDA receptor activation, and that it represents a neurotoxic event, the inhibition of which is able to reduce brain infarct area in a focal ischaemic event.