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 I 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. (c) 2006 Elsevier Inc. All rights reserved.