Costanza Prosperi, Carla Scali, Giancarlo Pepeu and Fiorella Casamenti*
Department of Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy
*Corresponding author. FAX: +39-055-4271280, E-mail: fiorella@pharm.unifi.it
Abstract: Brain inflammation underlies the pathogenesis of Alzheimer's disease (AD) and nonsteroidal anti-inflammatory drug therapy may delay the onset of AD. We investigated, in vivo, the effects of NO-flurbiprofen on brain inflammation in rats injected with quisqualic acid into the nucleus basalis and on the release of nitric oxide from the drug in naive rat brains. We showed that the excitotoxin-induced microglia reaction, the expression of inducible nitric oxide synthase-positive cells and the production of interleukin-1b and prostaglandin-E2 in the injected area were attenuated by the NO-flurbiprofen (15 mg/kg, p.o.) treatment. An oral administration of NO-flurbiprofen (25, 50 and 100 mg/kg) to naive rats was followed by significant increases in cortical nitrite levels. This drug may have important therapeutic implications for the treatment of AD.
Keywords: Nucleus basalis, Alzheimer's disease, Nitric oxide-releasing nonsteroidal anti-inflammatory drug, Inflammatory mediator
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