We studied the role of the amyloid precursor protein (APP) in @entity75 using @entity19 overexpressing APP. The middle cerebral artery (MCA) was occluded in FVB/ @entity19 expressing APP695.SWE (Swedish mutation) and in nontransgenic littermates. @entity1188 volume (cubic millimeters) was assessed 24 hr later in @entity10502 -stained brain sections. The @entity1188 produced by MCA occlusion was enlarged in the transgenics (+32 +/- 6%; n = 12; p < 0. 05; t test). Measurement of APP by ELISA revealed that, although relatively high levels of Abeta were present in the brain of the transgenics (Abeta1-40 = 80 +/- 19 pmol/g; n = 6), there were no differences between @entity63 and nonischemic hemispheres (p > 0.05). The reduction in cerebral blood flow produced by MCA occlusion at the periphery of the @entity63 territory was more pronounced in APP transgenics (-42 +/- 8%; n = 9) than in controls (-20 +/- 8%; n = 9). Furthermore, the vasodilatation produced by neocortical application of the endothelium-dependent vasodilator @entity934 (10 microM) was reduced by 82 +/- 5% (n = 8; p < 0.05) in APP transgenics. The data demonstrate that APP overexpression increases the susceptibility of the brain to @entity63 . The effect is likely to involve the Abeta-induced disturbance in endothelium-dependent vascular reactivity that leads to more severe @entity63 in regions at risk for @entity1188 . The cerebral vascular actions of peptides deriving from APP metabolism may play a role in the pathogenic effects of APP.

Increased susceptibility to XXXX in @entity19 overexpressing the amyloid precursor protein.

@entity63 :: ('MESH:D007511', 'Disease') :: ['ischemic injury', 'ischemia', 'ischemic'] @entity75 :: ('MESH:D001927', 'Disease') :: ['ischemic brain damage'] @entity19 :: ('10090', 'Species') :: ['N mice', 'transgenic mice'] @entity10502 :: ('CHEBI:52295', 'Chemical') :: ['thionin'] @entity1188 :: ('MESH:D007238', 'Disease') :: ['Infarct', 'infarct', 'infarction'] @entity934 :: ('MESH:D000109', 'Chemical') :: ['acetylcholine']
@entity75 :: (MESH:D001927,Disease) :: ['ischemic brain damage']
