Progressive increase in infarct size, neuroinflammation, and cognitive deficits in the presence of high levels of amyloid.
OBJECTIVE
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
beta-amyloid toxicity was modeled using bilateral intracerebroventricular injections of beta-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 beta-amyloid-treated rats that were even greater when beta-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.
Whitehead
Shawn N
SN
Department of Anatomy and Cell Biology, Medical Sciences Bldg, University of Western Ontario, London, Ontario, Canada.
Cheng
Guanliang
G
Hachinski
Vladimir C
VC
Cechetto
David F
DF
D000544:Alzheimer Disease / Q000473:pathology*; D000682:Amyloid / Q000096:biosynthesis*; D000818:Animals; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology*; D003072:Cognition Disorders / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008568:Memory; D009422:Nervous System Diseases / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000473:pathology; D013997:Time Factors
D000682:Amyloid