WHITE-MATTER ALTERATIONS FOLLOWING THROMBOEMBOLIC STROKE - A BETA-AMYLOID PRECURSOR PROTEIN IMMUNOCYTOCHEMICAL STUDY IN RATS

Thromboembolic stroke in rats leads to a well-described pattern of his topathological and behavioral abnormalities. However, limited data are available in animal models concerning the response of the white matte r to embolic events. The purpose of this study was to document pattern s of white matter abnormalities using P-amyloid precursor protein (bet a APP) immunocytochemistry as a: marker of axonal damage. Twelve male Wistar rats underwent photochemically induced right common carotid art ery thrombosis (CCAT) or sham procedures. At 3 days after CCAT, rats w ere perfusion-fixed and sections immunostained for the visualization o f beta APP or stained with hematoxylin and eosin for routine histopath ological analysis. As previously described, CCAT produced small ipsila teral embolic infarcts and ischemic cell change within gray matter str uctures including the medial cerebral cortex, striatum, hippocampus an d thalamus. In areas of frank infarction, numerous reactive profiles w ere observed within borderzones of the damaged site. However, beta APP immunocytochemistry also revealed reactive axonal profiles within var ious white matter tracts including the corpus callosum, external capsu le and fimbria of the hippocampus. In many cases, the presence of axon al damage could not be appreciated with routine hematoxylin and eosin staining. These data indicate that CCAT leading to platelet embolizati on to the brain not only produces embolic infarcts but also produces m ore subtle white matter abnormalities. Previously undetected white mat ter damage would be expected to participate in the sensorimotor and co gnitive behavioral deficits following embolic stroke.