GLIAL ACTIVATION AND WHITE-MATTER CHANGES IN THE RAT-BRAIN INDUCED BYCHRONIC CEREBRAL HYPOPERFUSION - AN IMMUNOHISTOCHEMICAL STUDY

Activation of glial cells and white matter changes (rarefaction of the white matter) induced in the rat brain by permanent bilateral occlusi on of the commom carotid arteries were immunohistochemically investiga ted up to 90 days. One day after ligation of the arteries, expression of the major histocompatibility complex (MHC) class I antigen in micro glia increased in the white matter including the optic nerve, optic tr act, corpus callosum, internal capsule, anterior commissure and traver sing fiber bundles of the caudoputamen. After 3 days of occlusion, MHC class I antigen was still elevated and in addition MHC class II antig en and leukocyte common antigen were up-regulated in the microglia in these same regions. Astroglia, labeled with glial fibrillary acidic pr otein, increased in number in these regions after 7 days of occlusion. A few lymphocytes, labeled with CD4 or CD8 antibodies, were scattered in the neural parenchyma 1 h after occlusion. Activation of glial cel ls and infiltration of lymphocytes persisted after 90 days of occlusio n in the white matter and the retinofugal pathway. However, cellular a ctivation and infiltration in microinfarcts of the gray matter was les s extensive and was substantially diminished 30 days after occlusion. The white matter changes were most intense in the optic nerve and opti c tract, moderate in the medial part of the corpus callosum, internal capsule and anterior commissure, and slight in the fiber bundles of th e caudoputamen. These results indicated that chronic cerebral hypoperf usion induced glial activation preferentially in the white matter. Thi s activation seemed to be an early indicator of the subsequent changes in the white matter.