Interaction between a rat model of cerebral ischemia and beta-amyloid toxicity: II. Effects of triflusal.
OBJECTIVE
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.
Whitehead
Shawn
S
Department of Anatomy and Cell Biology, University of Western Ontario, London, Canada.
Cheng
Guanliang
G
Hachinski
Vladimir
V
Cechetto
David F
DF
D000544:Alzheimer Disease / Q000276:immunology / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001253:Astrocytes / Q000378:metabolism; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D003342:Corpus Striatum / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D016232:Endothelins / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000494:pharmacology*; D013696:Temperature
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D016207:Cytokines; D016232:Endothelins; D005904:Glial Fibrillary Acidic Protein; C116337:OX-6 monoclonal antibody; D010455:Peptides; D012459:Salicylates; C016167:triflusal