In vivo brain inflammatory reactions in anumal models of Alzheimer’s disease: effects of selective and nonselective COX-2 inhibitors.

It has been shown that brain inflammatory processes contribute to the pathogenesis of Alzheimer's disease and that NSAIDs have a protective effect. This work investigated the effects of selective and non-selective COX-2 inhibitors on glia reaction, iNOS, COX-2 and MAPKs expression, nitrite levels, PGE2 and IL-1β formation and neurotransmitter functions following intracerebral injection of the excitotoxin quisqualic acid (QUIS) or β-amyloid peptide (1-42) (β-(1-42)) in the rats. QUIS (0.5ml of 0.12 M solution) or β-(1-42) (10 mg/ml) were injected into the right nucleus basalis (NB) of rats. Nimesulide (10 mg/kg/day), rofecoxib (3 mg/kg/day) and ibuprofen (12.5 mg/kg/day) were administered i.m. or p.o. for 7-28 days. The inflammatory reaction was stronger in the QUIS- than in β-(1-42)-injected animals. Both types of injection were followed by a rapid activation of glial cells. Many iNOS and MAPKs positive cells were observed at the injection site, at 24 h and 7 d post-injection. COX-2-ir in the NB microglial cells was detected 7 d after injection. Microdialysis revealed a transient increase in nitrite levels and a decrease in ACh release in the ipsilateral cortex. Seven d of nimesulide or ibuprofen treatment strongly attenuated microglia reaction, reduced the number of iNOS-positive cells and did not change the astrocytic reaction. The production of IL-1β and PGE2 in NB was reduced by nimesulide. The effects of pre-treatment as well as longer periods of nimesulide treatment on neurotransmitter function and the effects of rofecoxib, a selective COX-2 inhibitor, are under investigations.