AW rats with lesions exhibited significantly more anxiety than any other treatment group, while both lesion- and sham-operated TW rats were indistinguishable from vehicle-treated intact animals. Anxiety behaviors were observed pre- and post-surgery, and compared to levels at the peak of withdrawal. Acute PW (AW) rats received a full 16 mg/ml of progesterone for 7 days, and tapered PW (TW) rats received 5 days at full dosage, then 2 days with progressively halved dosages. Vehicle-treated rats received 2-hydroxypropyl-beta-cyclodextrin (HBC). Injections were administered at 1 and 6 h post-injury, then every 24 h for 7 days. Adult male Sprague-Dawley rats received either bilateral medial frontal cortex contusions or sham surgery.
Suddenly withdrawing progesterone after repeated dosing (PW) exacerbates ischemia and causes increased anxiety, seizure susceptibility, and excitotoxicity.
Systemic injections of the neurosteroid progesterone improve cognitive recovery after traumatic brain injury (TBI) and stroke, and decrease molecular indicators of neuronal damage.