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Stroke. 2005;36:1551-1556
Published online before print June 2, 2005, doi: 10.1161/01.STR.0000169933.88903.cf
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(Stroke. 2005;36:1551.)
© 2005 American Heart Association, Inc.


Original Contributions

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

Thomas van Groen, PhD; Kirsi Puurunen, PharmD; Hanna-Mari Mäki, MD; Juhani Sivenius, MD, PhD Jukka Jolkkonen, PhD

From Department of Neuroscience and Neurology (K.P., T.G., H-M.M., J.J.), University of Kuopio, Kuopio, Finland; and the Department of Neurology (J.S.), Kuopio University Hospital and Brain Research and Rehabilitation Center Neuron, Kuopio, Finland.

Correspondence to Jukka Jolkkonen, PhD, Department of Neuroscience and Neurology, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland. E-mail jukka.jolkkonen{at}uku.fi

Background and Purpose— The present study examined the long-term presence of ß-amyloid precursor protein (APP) and ß-amyloid (Aß) 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 Aß 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 Aß staining in axons in the corpus callosum and in neurons at the border of the ischemic region. APP and Aß 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 Aß and N-terminal APP, but not for C-terminal APP. Antibodies against the C-terminal of Aß, ie, Aß42 and Aß40, showed a preferential staining for Aß42. Congo red or thioflavine S did not stain the deposits.

Conclusions— The present results demonstrated the persistent presence and aggregation of APP and Aß, or their fragments, to dense plaque-like deposits in the ventroposterior lateral and ventroposterior medial nuclei of rats subjected to focal cerebral ischemia.


Key Words: amyloid • cerebral ischemia • rats • thalamus




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