beta-Amyloid precursor protein and ss-amyloid peptide immunoreactivity in the rat brain after middle cerebral artery occlusion: effect of age.
OBJECTIVE
Previous studies have shown that the ss-amyloid precursor protein (ssAPP) is upregulated after cerebral ischemia and that the ss-amyloid (Ass) 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 ssAPP and its proteolytic product Ass 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 ssAPP, Ass, 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. ssAPP 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. Ass immunoreactivity was evident in GFAP-positive astrocytic somata and processes, and also in clusters of small spherical structures in the penumbra. These Ass-immunoreactive minispheres were more numerous in aged rats than in young rats.


CONCLUSIONS
The presence of ssAPP and Ass immunoreactivity in the infarct core and penumbra indicates that cerebral ischemia promotes conditions that are favorable to the focal accumulation of ssAPP and its proteolytic fragments, especially in the aged brain.
Department of Neurology, Division of Warner-Lambert, Ann Arbor, Mich.
A
A
Popa-Wagner
E
E
Schröder
L C
LC
Walker
C
C
Kessler
D000375:Aging / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002536:Cerebral Arteries; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein