Chronic cerebral hypoperfusion-induced neuropathological changes in rats.

We investigated the time courses of histopathological changes in various brain regions following permanent occlusion of the bilateral common carotid arteries (2VO) in rats. 2VO rats exhibited rarefaction in the white matter, shrinkage of neurons in the cerebral cortex and hippocampus CA1-3 and dentate gyrus areas 1-3 days after the operation. These histological changes in the cortex and hippocampus were accompanied by a decrease in immunoreactivity for microtubule-associated protein 2 (MAP2), a marker protein of neuronal dendrites. Immunoreactivity for glial fibrillary acid protein (GFAP) was observed at 3-7 days after the 2VO operation. A marked increase in GFAP staining of the astrocytes in the cerebral cortex and hippocampus was found 30 days after ligation. Eight-arm radial maze performance was tested from 14 days to 60 days after the operation. The 2VO rats showed fewer initial correct responses than sham-operated control rats during a repeated training period. These findings suggested that the loss in dendritic MAP2 immunoreactivity and an increase in astroglial staining and/or rarefaction of the white matter may cause neuronal death, infarction and learning impairment under conditions of chronic hypoperfusion.