Progesterone improves long-term functional and histological outcomes after permanent stroke in older rats

• Progesterone was evaluated for neuroprotection in older rats with permanent stroke.
• Progesterone treatment improved long-term motor, sensory and learning function.
• Progesterone-treated animals showed attenuation of infarct volume.
• Progesterone treatment decreased glial fibrillary acidic protein expression.

Previous studies have shown progesterone to be beneficial in animal models of central nervous system injury, but less is known about its longer-term sustained effects on recovery of function following stroke. We evaluated progesterone’s effects on a panel of behavioral tests up to 8 weeks after permanent middle cerebral artery occlusion (pMCAO). Male Sprague-Dawley rats 12 m.o. were subjected to pMCAO and, beginning 3 h post-pMCAO, given intraperitoneal injections of progesterone (8 mg/kg) or vehicle, followed by subcutaneous injections at 8 h and then every 24 h for 7 days, with tapering of the last 2 treatments. The rats were then tested on functional recovery at 3, 6 and 8 weeks post-stroke. We observed that progesterone-treated animals showed attenuation of infarct volume and improved functional outcomes at 8 weeks after stroke on grip strength, sensory neglect, motor coordination and spatial navigation tests. Progesterone treatments significantly improved motor deficits in the affected limb on a number of gait parameters. Glial fibrillary acidic protein expression was increased in the vehicle group and considerably lowered in the progesterone group at 8 weeks post-stroke. With repeated post-stroke testing, sensory neglect and some aspects of spatial learning performance showed spontaneous recovery, but on gait and grip-strength measres progesterone given only in the acute stage of stroke (first 7 days) showed sustained beneficial effects on all other measures of functional recovery up to 8 weeks post-stroke.