From the Department of Neurology (A.P.-W., E.S., C.K.), University of
Greifswald, Germany; and Parke-Davis (L.C.W.), Division of Warner-Lambert, Ann
Arbor, Mich.
Correspondence to Aurel Popa-Wagner, PhD, Klinik für Neurologie, Ernst-Moritz-Arndt-Universität Greifswald, Ellernholzstr 1–2, 17487 Greifswald, Germany. E-mail wagner{at}neurologie.uni-greifswald.de
Background and Purpose—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.
Intermountain
Stroke Research Foundation,
Salt Lake City, Utah
© 1998 American Heart Association, Inc.
Original Contributions
ß-Amyloid Precursor Protein and ß-Amyloid Peptide Immunoreactivity in the Rat Brain After Middle Cerebral Artery Occlusion
Effect of Age
Editorial Comment
Effect of Age
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