PROTECTIVE EFFECT OF CYCLOSPORINE-A ON WHITE-MATTER CHANGES IN THE RAT-BRAIN AFTER CHRONIC CEREBRAL HYPOPERFUSION

Background and Purpose Activation of glial cells and rarefaction of th e white matter have been reported in rat brain after bilateral permane nt occlusion of the common carotid arteries. Using this model, we inve stigated the effects of the immunosuppressant cyclosporin A on the act ivation of glial cells and the white matter rarefaction. Methods Both common carotid arteries were ligated bilaterally in 40 male Wistar rat s. Twenty-two of these rats received an intraperitoneal injection of c yclosporin A, and the remaining 18 received a vehicle-solution injecti on. Microglia/macrophages were investigated with immunohistochemistry for the major histocompatibility complex class I and II antigens as we ll as for leukocyte common antigen. Astroglia were examined with glial fibrillary acidic protein as a marker. Activation of glial cells and white matter rarefaction were then investigated from 7 to 30 days afte r the ligation. Results In vehicle-treated animals, there was a persis tent and extensive activation of both microglia/macrophages and tract, corpus callosum, internal capsule, and traversing fiber bundles of th e caudoputamen. In cyclosporin A-treated rats, the number of activated microglia/macrophages was signifi cantly reduced (P < .01) to approxi mately one fifth of that in vehicle-treated animals. Similarly, rarefa ction of the white matter was much less intense in cyclosporin A-treat ed rats (P < .01). Conclusions Cyclosporin A suppressed both glial act ivation and white matter changes after chronic cerebral hypoperfusion. These results suggest that immunologic reaction may play a role in th e pathogenesis of the white matter changes and that the present model may be useful in investigating the pathophysiology of white matter cha nges induced by chronic cerebral hypoperfusion.