Transformation of Diffuse β-Amyloid Precursor Protein and β-Amyloid Deposits to Plaques in the Thalamus After Transient Occlusion of the Middle Cerebral Artery in Rats

Abstract

Background and Purpose— The present study examined the long-term presence of β-amyloid precursor protein (APP) and β-amyloid (Aβ) 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 Aβ 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 Aβ staining in axons in the corpus callosum and in neurons at the border of the ischemic region. APP and Aβ 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 Aβ and N-terminal APP, but not for C-terminal APP. Antibodies against the C-terminal of Aβ, ie, Aβ42 and Aβ40, showed a preferential staining for Aβ42. Congo red or thioflavine S did not stain the deposits. Conclusions— The present results demonstrated the persistent presence and aggregation of APP and Aβ, or their fragments, to dense plaque-like deposits in the ventroposterior lateral and ventroposterior medial nuclei of rats subjected to focal cerebral ischemia.