Progesterone Administration during Reperfusion, but not Preischemia Alone, Reduces Injury in Ovariectomized Rats

Abstract

Although progesterone is neuroprotective in traumatic brain injury, its efficacy in stroke is unclear. The authors determined whether there are infarction differences after middle cerebral artery occlusion (MCAO) in ovariectomized rats treated acutely with progesterone before MCAO or both pre- and postischemia. Rats received vehicle, 5 (P5), 10 (P10), or 20 (P20) mg/kg progesterone intraperitoneally 30 minutes before MCAO. In another cohort, animals received vehicle or 5 (P5R) mg/kg progesterone intraperitoneally 30 minutes before MCAO, at reperfusion initiation, and at 6-hour reperfusion. Animals underwent 2-hour MCAO by the intraluminal filament technique, followed by 22-hour reperfusion. Cortical (CTX) and caudate-putamen (CP) infarctions were determined by 2,3,5-triphenyltetrazolium chloride staining and digital image analysis. End-ischemic and early reperfusion regional cerebral blood flow (CBF) was measured by [14C]-iodoantipyrine quantitative autoradiography in vehicle- or progesterone (5 mg/kg)-treated rats. Cortical infarction (% contralateral CTX) was 31 ± 30% (vehicle), 39 ± 23% (P5), 41 ± 14% (P10), and 28 ± 20% (P20). Caudate-putamen infarction (% contralateral CP) was 45 ± 37% (vehicle), 62 ± 34% (P5), 75 ± 17% (P10), and 52 ± 30% (P20). In vehicle and P5R groups, CTX infarction was 37 ± 20% and *20 ± 17%, respectively (* P < 0.05 from vehicle). In vehicle and P5R groups, CP infarction was 63 ± 26% and 43 ± 29%, respectively. End-ischemic regional CBF and CBF recovery during initial reperfusion was unaffected by progesterone treatment. These data suggest that progesterone administration both before MCAO and during reperfusion decreases ischemic brain injury.