AMELIORATION BY CYCLOSPORINE-A OF BRAIN-DAMAGE FOLLOWING 5 OR 10 MIN OF ISCHEMIA IN RATS SUBJECTED TO PREISCHEMIC HYPERGLYCEMIA

It has recently been shown that the immunosuppressant cyclosporin A (C sA) dramatically ameliorates the selective neuronal necrosis which res ults from 10 min of forebrain ischemia in rats. Since CsA is a virtual ly specific blocker of the mitochondrial permeability transition (MPT) pore which is assembled under adverse conditions, such as mitochondri al calcium accumulation and oxidative stress, the results suggest that the delayed neuronal death is due to an MPT. In the present study we explored whether CsA can also ameliorate the aggravated brain damage w hich is observed in hyperglycemic subjects, and which encompasses rapi dly evolving neuronal lesions, edema, and postischemic seizures. Anaes thetised rats with a plasma glucose concentration of approximate to 13 mM were subjected to 10 min of forebrain ischemia, and allowed a reco very period of 7 days. In these animals, CsA prevented seizure from oc curring and virtually eliminated neuronal necrosis. In order to allow even higher plasma glucose values (approximate to 20 mM) to be studied , with long-term recovery, the duration of ischemia had to be reduced to 5 min. Again, CsA suppressed seizure activity and reduced neuronal damage. However, the effects were not as marked or consistent as in th e 10 min group, suggesting that excessive tissue acidosis recruits mec hanisms of damage which are not sensitive to CsA.