PROGESTERONE PROTECTS AGAINST LIPID-PEROXIDATION FOLLOWING TRAUMATIC BRAIN INJURY IN RATS

The gonadal hormone, progesterone, has been shown to have neuroprotect ive effects in injured nervous system, including the severity of posti njury cerebral edema. Progesterone's attenuation of edema is accompani ed by a sparing of neurons from secondary neuronal death and with impr ovements in cognitive outcome. In addition, we recently reported that postinjury blood-brain barrier (BBB) leakage, as measured by albumin i mmunostaining, was significantly lower in progesterone-treated than in nontreated rats, supporting a possible protective action of progester one on the BBB. Because lipid membrane peroxidation is a major contrib utor to BBB breakdown, we hypothesized that progesterone Limits this f ree radical-induced damage. An antioxidant action, neuroprotective in itself, would also account for progesterone's effects on the BBB, edem a, and cell survival after traumatic brain injury. To test progesteron e's possible antiperoxidation ef-fect, we compared brain levels of 8-i soprostaglandin F-2 alpha, (8-isoPGF(2 alpha)), a marker of Lipid pero xidation, 24, 48, and 72 h after cortical contusion in male rats treat ed with either progesterone or the oil vehicle. The brains of progeste rone-treated rats contained approximately one-third of the 8-isoPGF(2 alpha) found in oil-treated rats. These data suggest progesterone has antioxidant effects and support its potential as a treatment for brain injury.