PROTECTION FROM HYPOXIC AND N-METHYL-D-ASPARTATE INJURY WITH AZELASTINE, A LEUKOTRIENE INHIBITOR

The 5-lipoxygenase metabolites, leukotrienes, increase in concentratio n during cerebral ischemia. Azelastine is a new anti-allergic agent wh ich inhibits leukotriene C4 synthesis and release. We examined the neu roprotective properties of azelastine using the hippocampal slice. Aze lastine 15 muM significantly protected CA1 evoked responses from hypox ic injury, with CA1 population spike amplitude recovering to a mean 76 +/- 13% in azelastine treated slices, compared to 4 +/- 3% recovery i n paired unmedicated slices. The EC50 for this azelastine hypoxic prot ection was 9.8 muM. Azelastine additionally protected against injury i nduced by N-methyl-D-aspartate (NMDA), but not non-NMDA glutamate rece ptor agonists. No hypoxic protection was afforded by diphenhydramine 5 0 muM, suggesting that azelastine protection did not occur through his tamine H-1 receptor blockade. The finding of protection with azelastin e against hypoxic and NMDA-induced injury suggests that leukotriene pr oduction is a common pathway in these forms of neuronal injury, and th at leukotriene inhibition may be a useful neuroprotective strategy.