Progesterone inhibits ischemic brain injury in a rat model of permanent middle cerebral artery occlusion

Purpose: Previous studies suggest that progesterone (PROG) has a substantial protective effect against several types of brain injury. Since most cases of human stroke are caused by permanent occlusion of cerebral arteries, we assessed the neuroprotective effects of PROG on cerebral infarction and behavioral deficits in a permanent MCAO (pMCAO) model. Methods: pMCAO was produced by surgical insertion of a silicone-coated nylon filament into the right internal carotid artery. Laser-Doppler flowmetry was used to monitor cerebral blood flow for 10 min post-occlusion. PROG (8 mg/kg) or vehicle (2-hydroxypropyl-beta-cyclodextrin) was administered intraperitoneally at I h post-occlusion followed by subcutaneous injections at 6, 24 and 48 h post-occlusion. Measurements of infarct volumes (cortical, subcortical and total) were performed at 72 h and functional recovery, assessed by rotarod test, were performed 24, 48. and 72 h after pMCAO. Results: Following PROG treatment, stained sections revealed a significant reduction in cortical, caudate-putamen and hemispheric infarct volumes (% contralateral structure) compared to vehicle-injected controls. In addition, PROG treatment reduced functional deficits on the accelerating rotarod apparatus. Conclusion: We demonstrated and confirmed the neuroprotective effect of PROG using a permanent model of focal brain ischemia in rats.