Published Online
on December 9, 2004

A more recent version of this article appeared on January 1, 2005

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Submitted on June 22, 2004
Revised on August 27, 2004
Accepted on September 17, 2004

Interaction Between a Rat Model of Cerebral Ischemia and -Amyloid Toxicity. Inflammatory Responses

Shawn N. Whitehead BSc; Vladimir C. Hachinski MD; and David F. Cechetto PhD^*

From the Department of Anatomy and Cell Biology (S.N.W., D.F.C.), and the Faculty of Medicine and Dentistry (V.C.H.), University of Western Ontario, London, Canada.

^* To whom correspondence should be addressed. E-mail: cechetto{at}uwo.ca.

Background and Purpose--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 -amyloid (A[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--A 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 A(25-35). A(25-35) treatment decreased performance in the Montoya staircase behavioral test.

Conclusions--The enhanced inflammatory response with A 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.

Key words: Alzheimer disease • astrocytes • -amyloid • cytokines • reactive microglia

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