The Role of Proinflammatory Cytokines in Mediation of Brain Antiedema Effect of Female Sex Steroids Following Traumatic Brain Injury

Release of proinflammatory cytokines after traumatic brain injury (TBI) is a major cause of brain edema. Previous studies demonstrated that sex steroids decrease brain edema induced by TBI. In this study changes of brain cytokines after the administration of estrogen and progesterone 24 hours after TBI were evaluated.

Female rats were divided into 7 groups. Groups 1 and 2 were considered as control and sham respectively and other 5 groups underwent bilateral ovariectomy and considered as vehicle, physiologic does of estrogen (E1), pharmacologic dose of estrogen (E2), physiologic dose of progesterone (P1) and pharmacologic dose of progesterone (P2). Vehicle and sexual steroid hormones were injected intraperitoneally 30 minutes after TBI. Moderate TBI was induced by Marmarou method. Neurologic scores (VCS) were evaluated immediately, 1 h, 4 h and 24 h after TBI. Brain level of IL-1β, IL-6, TNF-α, TGF- estrogen and progesterone were measured 24 hours after TBI by ELISA method.

E1 and E2 groups showed respectively 27.5% and 27% decrease in brain level of IL-1β compared to vehicle. Brain level of IL-1β increased in vehicle group compared to sham. E1 and P1 groups showed respectively 47% and 20.5% decrease of brain IL-6 level compared to vehicle. Brain Level of TNF-α increased 48.5% in E2 group compared to the vehicle group. Both estrogen and progesterone in physiologic and pharmacologic doses increased TGF-β, but the highest increase of TGF-β level was about 9.5 times and was observed in E1 group. Brain level of β-Estradiol increased 1.8 times in E2 group and progesterone increased 1.84 times in P2 group compared to the vehicle group. Veterinary coma scale (VCS) increased in E1, E2, P1 and P2 group at 1 hour after TBI, whereas, 4 h after TBI only in E1 and P1 and 24 h after TBI, in E1, E2 and P1 groups VCS, showed increase.

Neuroprotective effect of sex hormones in reducing cerebral edema is probably performed by decrease of brain level of IL-1β and IL-6 and increase of brain level of TNF-α and TGF-β after TBI.