Interaction between a rat model of cerebral ischemia and beta-amyloid toxicity: inflammatory responses.
OBJECTIVE
Clinical data suggest that Alzheimer disease (AD) and stroke together potentiate cognitive impairment. Inflammatory mechanisms are involved in AD pathology and stroke and may be the mediator between AD and stroke toxicity.


METHODS
AD was modeled by cerebroventricular injections of beta-amyloid (Abeta[25-35]) and subcortical lacunar infarcts by striatal endothelin injections. Inflammatory mechanisms were examined using immunohistochemical analysis. Memory and motor tasks were assessed using the Montoya staircase test.


RESULTS
Abeta injections elicited increases in pathological and inflammatory correlates of AD in multiple forebrain sites. Increases in astrocytosis and reactive microglia in the hippocampus were enhanced with the combination of endothelin and Abeta(25-35). Abeta(25-35) treatment decreased performance in the Montoya staircase behavioral test.


CONCLUSIONS
The enhanced inflammatory response with Abeta toxicity and ischemia may mediate the inability to improve behavioral performance caused by the stroke. Anti-inflammatory treatment may ameliorate the pathological and behavioral deficits associated with the combination of AD and stroke.
Whitehead
Shawn N
SN
Department of Anatomy and Cell Biology, University of Western Ontario, London, Canada.
Hachinski
Vladimir C
VC
Cechetto
David F
DF
D000544:Alzheimer Disease / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000008:administration & dosage; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D002545:Brain Ischemia / Q000139:chemically induced / Q000150:complications*; D004396:Coloring Agents; D003224:Congo Red; D004195:Disease Models, Animal; D004660:Encephalitis / Q000139:chemically induced / Q000150:complications*; D016232:Endothelins / Q000008:administration & dosage; D005911:Gliosis / Q000139:chemically induced; D007150:Immunohistochemistry; D007267:Injections; D007858:Learning; D008297:Male; D009048:Motor Skills; D010446:Peptide Fragments / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D004396:Coloring Agents; D016232:Endothelins; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D003224:Congo Red