Hypoperfusion induces overexpression of beta-amyloid precursor protein mRNA in a focal ischemic rodent model

Silent stroke is one of the risk factors of dementia. In the present study, we used a novel focal ischemic animal model to investigate the effects of comparatively small changes of cerebral blood flow (CBF) on the expression of P-amyloid precursor protein (APP) mRNA. Focal ischemia was achieved by i ntroducing a 4-0 monofilament to the bifurcation of anterior and middle cer ebral arteries; Brain samples were harvested from ischemic core and penumbr a of cortices at 1, 4 and 7 days following ischemia. The expression of APP mRNA was assessed by RT-PCR. The CBF was decreased to 50% for 1 day after s troke and recovered to 90% at the fourth day after stroke. The changes of C BF were accompanied by an increase in the expression of APP mRNA. APP mRNA increased to 208% and 152% in the penumbra and core ischemic regions, respe ctively, on the fourth day after MCAO and remained high through the seventh day of ischemia. This study suggests brain hypoperfusion enhances APP mRNA expression and may contribute to the progression of cognitive impairment a fter silent stroke. (C) 2000 Elsevier Science B.V. All rights reserved.