The immunosuppressants cyclosporin A and FK506 equally ameliorate brain damage due to 30-min middle cerebral artery occlusion in hyperglycemic rats.
In the present experiments, we compared the anti-ischemic effects of the immunosuppressants cyclosporin A (CsA) and FK506 in hyperglycemic animals subjected to 30 min of middle cerebral artery (MCA) occlusion. Both immunosuppressants were given as pre-treatment, the effect of treatment being evaluated by 2,3, 5-triphenyltetrazolium (TTC) staining after 3 days of recovery. Both FK506 and CsA reduced the infarct volume to less than 1/3 of control. In spite of CsA's known effect as a blocker of the mitochondrial transition (MPT) pore, it failed to give a more robust effect than FK506. If anything, FK506, which lacks an effect on the MPT pore, had a more pronounced anti-ischemic effect. We conclude that, in this model of infarction, an MPT may not play a major pathogenetic role.
Center for the Study of Neurological Diseases, The Neuroscience Institute, Queen's Medical Center, 1356 Lusitana Street, 8th floor, Honolulu, HI 96813, USA.
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D000704:Analysis of Variance; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000188:drug therapy*; D002544:Cerebral Infarction / Q000188:drug therapy / Q000209:etiology; D016572:Cyclosporine / Q000627:therapeutic use*; D006943:Hyperglycemia / Q000150:complications; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D018696:Neuroprotective Agents; D016572:Cyclosporine; D016559:Tacrolimus