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 histopathological and behavioral abnormalities. However, limited data are available in animal models concerning the response of the white matter to embolic events. The purpose of this study was to document patterns of white matter abnormalities using beta-amyloid precursor protein (betaAPP) immunocytochemistry as a marker of axonal damage. Twelve male Wistar rats underwent photochemically induced right common carotid artery thrombosis (CCAT) or sham procedures. At 3 days after CCAT, rats were perfusion-fixed and sections immunostained for the visualization of betaAPP or stained with hematoxylin and eosin for routine histopathological analysis. As previously described, CCAT produced small ipsilateral embolic infarcts and ischemic cell change within gray matter structures including the medial cerebral cortex, striatum, hippocampus and thalamus. In areas of frank infarction, numerous reactive profiles were observed within borderzones of the damaged site. However, betaAPP immunocytochemistry also revealed reactive axonal profiles within various white matter tracts including the corpus callosum, external capsule and fimbria of the hippocampus. In many cases, the presence of axonal damage could not be appreciated with routine hematoxylin and eosin staining. These data indicate that CCAT leading to platelet embolization to the brain not only produces embolic infarcts but also produces more subtle white matter abnormalities. Previously undetected white matter damage would be expected to participate in the sensorimotor and cognitive behavioral deficits following embolic stroke.