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

Background & Aims: 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 ۲۴ hours after TBI were evaluated. Materials and Methods: Female rats were divided into ۷ groups. Groups ۱ and ۲ were considered as control and sham respectively and other ۵ groups underwent bilateral ovariectomy and considered as vehicle, physiologic does of estrogen (E۱), pharmacologic dose of estrogen (E۲), physiologic dose of progesterone (P۱) and pharmacologic dose of progesterone (P۲). Vehicle and sexual steroid hormones were injected intraperitoneally ۳۰ minutes after TBI. Moderate TBI was induced by Marmarou method. Neurologic scores (VCS) were evaluated immediately, ۱ h, ۴ h and ۲۴ h after TBI. Brain level of IL-۱, IL-۶, TNF-, TGFestrogen and progesterone were measured ۲۴ hours after TBI by ELISA method. Results: E۱ and E۲ groups showed respectively ۲۷.۵% and ۲۷% decrease in brain level of IL-۱ compared to vehicle. Brain level of IL-۱ increased in vehicle group compared to sham. E۱ and P۱ groups showed respectively ۴۷% and ۲۰.۵% decrease of brain IL-۶ level compared to vehicle. Brain Level of TNF- increased ۴۸.۵% in E۲ group compared to the vehicle group. Both estrogen and progesterone in physiologic and pharmacologic doses increased TGF-, but the highest increase of TGF- level was about ۹.۵ times and was observed in E۱ group. Brain level of -Estradiol increased ۱.۸ times in E۲ group and progesterone increased ۱.۸۴ times in P۲ group compared to the vehicle group. Veterinary coma scale (VCS) increased in E۱, E۲, P۱ and P۲ group at ۱ hour after TBI, whereas, ۴ h after TBI only in E۱ and P۱ and ۲۴ h after TBI, in E۱, E۲ and P۱ groups VCS, showed increase. Conclusion: Neuroprotective effect of sex hormones in reducing cerebral edema is probably performed by decrease of brain level of IL-۱ and IL-۶ and increase of brain level of TNF- and TGF- after TBI. Ke

کلیدواژه ها:

Brain injury ، estrogen ، Progesterone ، IL-۱ ، IL-۶ ، TNF- ، TGF-