Interaction Between a Rat Model of Cerebral Ischemia and β-Amyloid Toxicity

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 β-amyloid (Aβ25–35) 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 Aβ or endothelin alone but was less effective in the more severe pathology of the combined Aβ/endothelin model. Conclusions— Higher doses or more prolonged treatment with NSAIDs may be required for more effective neuroprotection in combined AD and stroke conditions.