Published Online
on June 2, 2005

A more recent version of this article appeared on July 1, 2005

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Submitted on November 12, 2004
Revised on January 21, 2005
Accepted on March 7, 2005

Transformation of Diffuse -Amyloid Precursor Protein and -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; and 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.

^* To whom correspondence should be addressed. E-mail: jukka.jolkkonen{at}uku.fi.

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, A42 and A40, showed a preferential staining for A42. Congo red or thioflavine S did not stain the deposits.

Conclusions--The present results demonstrated the persistent presence and aggregation of APP and A, 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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