Mechanisms of the neuroprotective effect of aspirin after oxygen and glucose deprivation in rat forebrain slices

Acetylsalicylic acid (ASA, Aspirin) is an anti-inflammatory drug with a wid e spectrum of pharmacological activities and multiple sites of action. Apar t from its preventive actions against stroke due to its antithrombotic prop erties, recent data in the literature suggest that high concentrations of A SA also exert direct neuroprotective effects. We have used an in vitro mode l of brain ischaemia using rat forebrain slices deprived of oxygen and gluc ose to test ASA neuroprotective properties. We have found that ASA inhibits neuronal damage at concentrations lower than those previously reported (0. 1-0.5 mM), and that these effects correlate with the inhibition of excitato ry amino acid release, of NF-KB translocation to the nucleus and iNOS expre ssion caused by ASA. All of these three mechanisms may mediate the neuropro tective effects of this drug. Our results also show that the effects of ASA are independent of COX inhibition. Taken together, our present findings sh ow that ASA is neuroprotective in an in vitro model of brain ischaemia at d oses close to those recommended for its antithrombotic effects. (C) 2000 El sevier Science Ltd. All rights reserved.