AZELASTINE PROTECTS AGAINST CA1 TRAUMATIC NEURONAL INJURY IN THE HIPPOCAMPAL SLICE

Activation of NMDA receptors appears to play a important role in traum atic neuronal injury. Additionally, N-methyl-D-aspartate (NMDA) excito toxicity may involve leukotriene production. Therefore, we investigate d whether azelastine, an anti-allergic agent inhibiting the synthesis and release of leukotrienes, could protect against CA1 traumatic neuro nal injury in the hippocampal slice. Fluid percussion trauma produced evidence of severe neuronal injury with CA1 antidromic population spik e amplitude recovering after 95 min to only a mean 16 +/- 1% S.E. of i nitial amplitude. With 15 mu M azelastine treatment given after trauma for 35 min this recovery improved to 112 +/- 17%. The azelastine EC(5 0) for this protection was 10 mu M Significant protection was also see n with azelastine application begun 15 min after trauma. Azelastine al so protected the ability to induce long-term potentiation after trauma . The specific leukotriene inhibitors, MK-571 and MK-886, similarly pr ovided significant neuroprotection. These findings suggest that CAI tr aumatic neuronal injury may be mediated by leukotriene production.