Background and Purpose-The present study examined the long-term presence of ␤-amyloid precursor protein (APP) and ␤-amyloid (A␤) accumulation in the rat thalamus after focal cerebral ischemia. Methods-Male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 hours.Sensorimotor outcome was assessed using a tapered/ledged beam-walking task after operation. The distribution of APP and A␤ was examined immunohistochemically at 1 week, 1 month, and 9 months after MCAO. Results-MCAO caused a long-lasting deficit in forelimb and hind limb function assessed using the beam-walking test.Histologic examination revealed a transient increase in APP and A␤ staining in axons in the corpus callosum and in neurons at the border of the ischemic region. APP and A␤ deposits persisted in the thalamic nuclei (ventroposterior lateral and ventroposterior medial nuclei), eventually leading to dense plaque-like deposits by the end of the 9-month follow-up. The deposits were surrounded by an astroglial scar. The deposits were positive for A␤ and N-terminal APP, but not for C-terminal APP. Antibodies against the C-terminal of A␤, ie, A␤42 and A␤40, showed a preferential staining for A␤42. Congo red or thioflavine S did not stain the deposits. Key Words: amyloid Ⅲ cerebral ischemia Ⅲ rats Ⅲ thalamus B eta (␤)-amyloid precursor protein (APP) is a transmembrane protein with a long extracellular N-terminal and short intracellular C-terminal domain. APP is widely expressed in the brain, where its abnormal upregulation can lead to the accumulation of ␤-amyloid (A␤), for example in Down syndrome patients. 1,2,3 A␤ is a hydrophobic self-aggregating peptide consisting of 40 to 42 residues, derived by sequential processing of the ␤-amyloid precursor protein by ␤-secretase and ␥-secretase. 4 A␤ is a major component of senile plaques and is one of the pathologic hallmarks of Alzheimer disease. 5 Brain trauma leads to the accumulation of a number of proteins, mostly as a consequence of the interruption of fast anterograde axonal transport. 6 The accumulated proteins include APP and its proteolytic product A␤, neurofilament proteins, and synuclein proteins. Accumulated proteins usually disappear over time, 7 but APP has been detected for up to 1 year after injury. 8 Cerebral ischemia also leads to a transient upregulation and accumulation of APP. 9,10 For example, APP staining and expression are detected in the subcortical white matter and adjacent to the boundary of the ischemic lesion in the gray matter after transient occlusion of the middle cerebral artery (MCAO). 10 -13 These studies, however, used only short survival periods ranging from days to weeks. The aim of the present study was to assess possible long-term accumulation of APP and A␤ during a 9-month follow-up in rats subjected to transient MCAO. Conclusions-The Materials and Methods AnimalsMale Wistar rats (3 months old, 285 to 325 grams at the beginning of the study; National Laboratory Animal Centre, Kuopio, Finland) were used in the present study. The ani...

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