Neuroprotective effect of postischemic administration of progesterone in spontaneously hypertensive rats with focal cerebral ischemia

Object. Exogenous progesterone has been shown to reduce brain edema and isc hemia-induced cell damage and to improve physiological and neurological fun ction during the early stage of focal cerebral ischemia. In the present stu dy, the authors assessed the neuroprotective potential of progesterone duri ng the late stage of ischemia in a transient middle cerebral artery (MCA) o cclusion model in the rat. Methods. Forty-eight male spontaneously hypertensive rats were randomly ass igned to six groups. Progesterone was dissolved in dimethyl sulfoxide (DMSO ). In four groups of rats, the dissolved progesterone (4 mg/kg or 8 mg/kg) was administered for 2 or 7 days after ischemia. In two control groups DMSO was administered for 2 or 7 days after ischemia. Occlusion of the MCA was induced by insertion of an intraluminal suture, and reperfusion was accompl ished by withdrawal of the suture. Treatment was initiated on reperfusion, which followed 2 hours of MCA occlusion, and continued once a day. Lesion v olume, neurological deficit, and body weight loss were measured 2 or 7 days after ischemia, depending on the animal group. Treatment with a high dose of progesterone (8 mg/kg) resulted in reductions in lesion size, neurological deficits, and body weight, compared with cont rol rats. Conclusions. Administration of progesterone to male rats 2 hours after MCA occlusion reduces ischemic brain damage and improves neurological deficit e ven 7 days after ischemia.