β-Amyloid Precursor Protein and β-Amyloid Peptide Immunoreactivity in the Rat Brain After Middle Cerebral Artery Occlusion

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Abstract
Background and Purpose —Previous studies have shown that the β-amyloid precursor protein (βAPP) is upregulated after cerebral ischemia and that the β-amyloid (Aβ) fragment may be toxic to brain cells. Although stroke in humans usually afflicts the elderly, most experimental studies on the nature of cerebral ischemia have used young animals. To test the hypothesis that the upregulation and/or persistence of amyloidogenic proteins is exacerbated in aged rats after cerebral ischemic stroke, we studied the expression of βAPP and its proteolytic product Aβ in the brains of young and old rats 7 days after temporary cerebral ischemia. Methods —Focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3- and 20-month-old male Sprague-Dawley rats. After 1 week, brains were removed and immunostaining was performed for βAPP, Aβ, and ED1 for macrophages and glial fibrillary acidic protein (GFAP). Results —Histological staining revealed that the degree of necrotic cavitation in the infarct core was relatively less in aged rats than in young rats, suggesting a slower pace of degenerative change and/or tissue removal in older animals. βAPP immunoreactivity was robustly increased, primarily in macrophage-like, ED1-positive cells in the infarct core and in the penumbra of both young and aged animals. Aβ immunoreactivity was evident in GFAP-positive astrocytic somata and processes, and also in clusters of small spherical structures in the penumbra. These Aβ-immunoreactive minispheres were more numerous in aged rats than in young rats. Conclusions —The presence of βAPP and Aβ immunoreactivity in the infarct core and penumbra indicates that cerebral ischemia promotes conditions that are favorable to the focal accumulation of βAPP and its proteolytic fragments, especially in the aged brain.

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