H. Wakita et al., PROTECTIVE EFFECT OF CYCLOSPORINE-A ON WHITE-MATTER CHANGES IN THE RAT-BRAIN AFTER CHRONIC CEREBRAL HYPOPERFUSION, Stroke, 26(8), 1995, pp. 1415-1422
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.