Slow-release and injected progesterone treatments enhance acute recovery after traumatic brain injury.

The benefits of continuous progesterone release via subcutaneous silastic capsule implants were compared to daily subcutaneous injections in a rat model of traumatic brain injury (TBI). Adult male Sprague-Dawley rats received either bilateral frontal cortex contusions or sham surgery. Rats were injected with progesterone or vehicle at 1 and 6 h post-injury, then once every 24 h for six days with tapering of the dose over the final two treatments. Progesterone-packed silastic capsules were implanted post-injury while the animals were anesthetized. Behavioral assays for anxiety and locomotor activity were evaluated pre- and post-TBI. Brains were extracted eight days post-TBI and prepared for molecular assays. Decreased GABAA-4 levels complemented a decrease in anxiety behaviors on the Elevated Plus Maze for capsule compared to progesterone-injected animals prior to daily injections. All groups with implanted capsules increased locomotor activity compared to those given progesterone injections. In conclusion, steady-state progesterone treatment after TBI decreases edema and anxiety and increases activity, thus enhancing behavioral recovery. A continuous mode of pharmacological administration may prove to be more beneficial in translational and clinical testing than bolus injections over the same period of time.