Interaction between a rat model of cerebral ischemia and beta-amyloid toxicity: II. Effects of triflusal.

Abstract

BACKGROUND AND PURPOSE: Clinical data suggest that Alzheimer disease (AD) and stroke together potentiate cognitive impairment. Our rat model demonstrates that this interaction may be mediated through inflammatory cells and pathways. Thus, anti-inflammatory agents such as Triflusal, a nonsteroidal anti-inflammatory agent (NSAID), may provide neuroprotection for susceptible neurons in AD and cerebral ischemia. METHODS: AD was modeled by cerebroventricular injections of beta-amyloid (Abeta25-35) and subcortical lacunar infarcts by striatal endothelin injections. Inflammatory mechanisms were examined by immunohistochemical analysis. Behavioral tasks were assessed with the Montoya staircase test. RESULTS: Triflusal reduced pathologic and inflammatory markers and functional deficits in rats receiving Abeta or endothelin alone but was less effective in the more severe pathology of the combined Abeta/endothelin model. CONCLUSIONS: Higher doses or more prolonged treatment with NSAIDs may be required for more effective neuroprotection in combined AD and stroke conditions.