Progesterone is neuroprotective after transient middle cerebral artery occlusion in male rats

Progesterone (FROG) is a neurosteroid, possessing a variety of functions in the central nervous system. Exogenous FROG has been shown to reduce secondary neuronal loss in conjunction with attenuated brain edema after cerebral contusion and to reduce brain edema after focal cerebral ischemia. In the present study, we assessed the neuroprotective potential of FROG in a model of focal cerebral ischemia in the rat. Forty-eight male Wistar rats were randomly assigned to 4 groups, i.e. pretreatment with water soluble FROG, or dimethyl sulfoxide (DMSO) dissolved FROG, or DMSO as control or delayed treatment with DMSO dissolved FROG. Middle cerebral artery occlusion (MCAO) was induced by insertion of an intraluminal suture and reperfusion was performed by withdrawing the suture. Pretreatments were initiated 30 min before MCAO via intraperitoneal injection. Delayed treatment was initiated upon reperfusion following 2 h of MCAO. Infarct volume, body weight loss, and neurological deficit were measured 48 h after MCAO. Pre- and delayed treatment with DMSO dissolved FROG resulted in a 39% (P < 0.05) and 34% (P < 0.05) reduction in cerebral infarction, respectively, along with decreased body weight loss and improved neurological function as compared to control animals, whereas no statistically significant reduction in infarct volume by water soluble FROG was found. We demonstrated that administration of FROG to the male rat before or 2 hours after onset of MCAO reduces ischemic cell damage and improves physiological and neurological function 2 days after stroke. These results suggests potential therapeutic properties of FROG in the management of stroke.