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

Background and Purpose - The present study examined the long-term presence of beta-amyloid precursor protein (APP) and beta-amyloid (A beta) 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 beta 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 beta staining in axons in the corpus callosum and in neurons at the border of the ischemic region. APP and A beta 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 beta and N-terminal APP, but not for C-terminal APP. Antibodies against the C-terminal of A beta, ie, A beta 42 and A beta 40, showed a preferential staining for A beta 42. Congo red or thioflavine S did not stain the deposits. Conclusions - The present results demonstrated the persistent presence and aggregation of APP and A beta, or their fragments, to dense plaque-like deposits in the ventroposterior lateral and ventroposterior medial nuclei of rats subjected to focal cerebral ischemia.