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(Stroke. 2007;38:3245.)
© 2007 American Heart Association, Inc.

Original Contributions

Progressive Increase in Infarct Size, Neuroinflammation, and Cognitive Deficits in the Presence of High Levels of Amyloid

Shawn N. Whitehead, PhD; Guanliang Cheng, MD; Vladimir C. Hachinski, MD David F. Cechetto, PhD

From the Faculty of Medicine and Dentistry, Department of Anatomy and Cell Biology (S.N.W., G.C., D.F.C.), University of Western Ontario, London, Canada; and the Department of Clinical Neurology (V.C.H.), London Health Sciences Research Centre, University of Western Ontario, London, Canada.

Correspondence to David F. Cechetto, Department of Anatomy and Cell Biology, Medical Sciences Bldg, University of Western Ontario, London, Ontario, Canada N6A 5C1. E-mail cechetto{at}uwo.ca

Background and Purpose— In the elderly, cerebral ischemia (CI) occurs in the presence of high levels of amyloid. Neuroinflammation plays a critical role in the pathophysiology of Alzheimer’s disease and CI. This study examined infarct size, neuroinflammation, and cognitive deficits over time in rat models of Alzheimer’s disease and CI.

Methods— ß-amyloid toxicity was modeled using bilateral intracerebroventricular injections of ß-amyloid 25 to 35 peptides. CI was modeled using unilateral injections of the potent vasoconstrictor, endothelin-1, into the striatum.

Results— Infarct volumes were higher in the presence of amyloid and compared with the CI model alone. In the CI model alone, the infarct volume was significantly smaller 28 days after surgery compared with 7 days after surgery. However, when Alzheimer’s disease and CI models were combined, the infarct volume was significantly larger 28 days after surgery compared with 7 days after surgery. The neuroinflammation in the region of the infarct was also significantly increased. The Barnes circular platform test showed time-dependent increases in memory and learning deficits in the ß-amyloid-treated rats that were even greater when ß-amyloid treatment was combined with CI.

Conclusions— CI in the presence of high levels of amyloid results in progressive increases in infarct size, neuroinflammation, and cognitive deficits.

Key Words: Aß peptide • Alzheimer’s disease • memory • neuroinflammation • rat • stroke