PROTECTIVE EFFECT OF N-(3-(AMINOMETHYL BENZYL) ACETAMIDINE, AN INDUCIBLE NITRIC-OXIDE SYNTHASE INHIBITOR, IN BRAIN-SLICES EXPOSED TO OXYGEN-GLUCOSE DEPRIVATION

It has been suggested that large amounts of nitric oxide (NO) produced by inducible NO synthase are involved in the mechanisms of neurotoxic ity after cerebral ischaemia. We have recently demonstrated that induc ible NO synthase was expressed within hours after rat forebrain slices were exposed to oxygen-glucose deprivation. Therefore, we sought to d etermine whether NO produced by inducible NO synthase contributes to t issue damage in this model, by using a new, highly selective, inhibito r of inducible NO synthase, N-(3-(aminomethyl)benzyl)acetamidine (1400 W). We found that incubation with 1400W from the start of the oxygen-g lucose deprivation period until the end of the experiment decreases ti ssue damage determined as lactate dehydrogenase (LDH) efflux 4 h after the oxygen-glucose deprivation period, the time at which inducible NO synthase expression is maximal in this model. This effect may be a re sult of direct inhibition of inducible NO synthase activity, raising t he possibility of a clinical use of selective inhibitors of this NO sy nthase isoform in the management of cerebral ischaemia. (C) 1998 Elsev ier Science B.V. All rights reserved.