The effects of a novel NSAID on chromic neuroinflammation are age dependent

Chronic inflammation may play an important role in the pathogenesis of Alzh eimer's disease (AD). The present study compared the effects of chronic neu roinflammation, produced by infusion of lipopolysaccharide (LPS) into the f ourth ventricle, upon memory in young, adult, and old rats. Nonsteroidal an ti-inflammatory drug (NSAID) therapy may delay the onset of AD. We show tha t NO-Flurbiprofen (NFP), a novel NSAID that lacks gastrointestinal side eff ects, attenuated the neuroinflammatory reaction and reduced the inflammatio n-induced memory deficit. Chronic LPS infusions impaired performance of you ng rats but not adult or old rats. Treatment with NFP improved the performa nce of LPS-infused young rats, but not LPS-infused adult or old rats. I,PS infusions increased the number of activated microglia in young and adult ra ts but not old rats. NFP treatment attenuated the effects of LPS upon micro glia activation in young and adult rats, but not old rats. The results sugg est that NSAID therapies designed to influence the onset of AD should be in itiated in adults before age-associated inflammatory processes within the b rain have a chance to develop. (C) 1999 Elsevier Science Inc. All rights re served.