Protective effect of cyclosporin a on white matter changes in the rat brain after chronic cerebral hypoperfusion

Hideaki Wakita, Hidekazu Tomimoto, Ichiro Akiguchi, Jun Kimura

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Activation of glial cells and rarefaction of the white matter have been reported in rat brain after bilateral permanent occlusion of the common carotid arteries. Using this model, we investigated the effects of the immunosuppressant cyclosporin A on the activation of glial cells and the white matter rarefaction. Methods Both common carotid arteries were ligated bilaterally in 40 male Wistar rats. Twenty-two of these rats received an intraperitoneal injection of cyclosporin A, and the remaining 18 received a vehicle-solution injection. Microglia/macrophages were investigated with immunohistochemistry for the major histocompatibility complex class I and II antigens as well 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 after the ligation. Results In vehicle-treated animals, there was a persistent and extensive activation of both microglia/macrophages and astroglia in the white matter, including the optic nerve, optic tract, corpus callosum, internal capsule, and traversing fiber bundles of the caudoputamen. In cyclosporin A-treated rats, the number of activated microglia/macrophages was significantly reduced (P less than.01) to approximately one fifth of that in vehicle-treated animals. Similarly, rarefaction of the white matter was much less intense in cyclosporin A-treated rats (P less than.01). Conclusions Cyclosporin A suppressed both glial activation and white matter changes after chronic cerebral hypoperfusion. These results suggest that immunologic reaction may play a role in the pathogenesis of the white matter changes and that the present model may be useful in investigating the pathophysiology of white matter changes induced by chronic cerebral hypoperfusion.

Original languageEnglish
Pages (from-to)1415-1422
Number of pages8
JournalStroke
Volume26
Issue number8
DOIs
Publication statusPublished - 08-1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

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