Progesterone Protects against Necrotic Damage and Behavioral Abnormalities Caused by Traumatic Brain Injury

Abstract

A single injection of progesterone can attenuate cerebral edema when administered during the first 24 h after traumatic brain injury (TBI) in rats but this regimen may not always produce functional benefits. In this experiment, we sought to find the duration of progesterone administration needed to facilitate both behavioral and morphological recovery. Male rats received bilateral contusions of the medial prefrontal cortex and were given progesterone (4 mg/kg) or vehicle for 3 or 5 days postoperatively. Both the 3- and the 5-day progesterone regimens reduced the size of injury- induced necrosis and cell loss, with the 5-day schedule being most effective. With regard to behavioral outcome, only 5 days of progesterone injections resulted in improved spatial learning performance and reduced sensory neglect. These results show that 5 days of postinjury progesterone treatment are needed to reduce significantly the neuropathological and behavioral abnormalities found in a rodent model of TBI. These benefits of progesterone, in the absence of any known side effects, provide further support for clinical testing of this neurosteroid.