PROTECTIVE EFFECT OF THE 5-LIPOXYGENASE INHIBITOR AA-861 ON CEREBRAL EDEMA AFTER TRANSIENT ISCHEMIA

This study examined the effect of AA-861, a specific 5-lipoxygenase in hibitor, on brain levels of leukotriene C-4 (LTC(4)) and correlated an y changes with changes in edema formation and cerebral blood flow (CBF ) after transient ischemia In gerbils. Brain levels of LTC(4) were obs erved to be increased at 1, 2, and 6 hours of reperfusion following 20 minutes of occlusion. At 2 hours of reperfusion, a pretreatment dose of 1000 mg/kg of AA-861 was required to inhibit more than 90% of the r eperfusion-induced increases in brain LTC(4). At this dose, inhibition of LTC(4) production was observed at 2 and 6 hours of reperfusion. Th e specific gravity of both the cortex and subcortex was decreased at 6 hours of reperfusion after 20 minutes of occlusion. At 2 hours of rep erfusion, no significant difference was observed in the specific gravi ty of the cortex and subcortex regions of gerbils pretreated with AA-8 61 or with vehicle, but at 6 hours of reperfusion significant positive differences were observed. Cerebral blood flow decreased to approxima tely 10% of preocclusion values during occlusion and returned to near- preocclusion values after 10 minutes of reperfusion. No significant di fferences were observed in regional CBF in the AA-861- and vehicle-pre treated gerbils during reperfusion. These findings indicate that LTC(4 ) production after transient cerebral ischemia may be an important con tributor to the development of cerebral edema and that CBF does not me diate the LTC(4)-involved development of edema.