Efficacy of progesterone following a moderate unilateral cortical contusion injury

Abstract

Traumatic brain injury (TBI) results in an accumulation of edema and loss of brain tissue. Progesterone (PROG) has been reported to reduce edema and cortical tissue loss in a bilateral prefrontal cortex injury. This study tests the hypothesis that PROG is neuroprotective following a unilateral parietal cortical contusion injury (CCI). Adult male Sprague-Dawley rats were subjected to a moderate unilateral TBI using the CCI model. Rats were given 8 mg/kg PROG 15 min post-injury with four subsequent injections (6 h, and days 1, 2, and 3). Edema was determined 3 days post-injury, while cortical tissue sparing was also evaluated at 7 days post-injury. Animals were injured and given one of four treatments: (I) vehicle; (II) low dose: 8 mg/kg PROG; (III) high dose: 16 mg/kg PROG; (IV) tapered: 8 mg/kg PROG. Animals were given an initial injection within 15 min, followed by five injections (6 h, and days 1, 2, 3, and 4). Group IV received two additional injections (4 mg/kg on day 5; 2 mg/kg on day 6). PROG failed to alter both cortical edema and tissue sparing at any dose. Failure to modify two major sequelae associated with TBI brings into question the clinical usefulness of PROG as an effective treatment for all types of brain injury.

FIG. 1.

The regions of the rat cortex that were used for analysis for percent water content (edema) following injury are shown. Rats given either vehicle (peanut oil) or 8 mg/kg progesterone (PROG) treatments were killed 3 days post-injury and their brains harvested. Brains were cut in a brain matrix (A), resulting in 11 different brain regions (B), and only the dorsal portions containing the injury and penumbral brain tissue were obtained from both hemispheres (C). The X symbol represents portions not used in percent water content analysis. The four regions contained the impact site, corresponding contralateral tissue, and penumbral tissue from the ipsi- and contralateral sides.

FIG. 2.

All animals in this study showed obvious cortical damage 7 days post-injury. Statistical analysis found no differences between vehicle-treated animals compared to those given progesterone (PROG). Previous research suggests administering PROG for 5 days or given for 7 days in a tapered withdrawal manner is neuroprotective. Animals given tapered PROG treatment achieved no greater tissue sparing than animals given the vehicle alone. Vehicle-treated (peanut oil) animals demonstrated 78.5 ± 9.6% tissue sparing, while tapered treated rats maintained 81.5 ± 10.1% sparing p > 0.1, suggesting that PROG is not neuroprotective in this injury model. Points indicate individual values. Horizontal line represents the group mean.

FIG. 3.

The region of cortex that contained injury showed a significant increase in percent water content compared to corresponding contralateral tissue and penumbral tissue. Progesterone (PROG) failed to reduce edema in the area containing the injury and had no effect on any other tissue region. *p < 0.01 compared to all other brain regions and treatment groups.