NO-flurbiprofen attenuates excitotoxin-induced brain inflammation, and releases nitric oxide in the brain

Brain inflammation underlies the pathogenesis of Alzheimer's disease (AD) a nd nonsteroidal anti-inflammatory drug therapy may delay the onset of AD. W e investigated, in vivo, the effects of NO-flurbiprofen on brain inflammati on in rats injected with quisqualic acid into the nucleus basalis and on th e release of nitric oxide from the drug in naive rat brains. We showed that the excitotoxin-induced microglia reaction, the expression of inducible ni tric oxide synthase-positive cells and the production of interleukin-1 beta and prostaglandin-E-2 in the injected area were attenuated by the NO-flurb iprofen (15 mg/kg, p.o.) treatment. An oral administration of NO-flurbiprof en (25, 59 and 100 mg/kg) to naive rats was followed by significant increas es in cortical nitrite levels. This drug may have important therapeutic imp lications for the treatment of AD.