Possible involvement of female sex steroid hormones in intracellular signal transduction mediated by cytokines following traumatic brain injury

Introduction: The aim of this study was to determine the anti-inflammatory effect of female sex hormones on the level of intracellular molecules of cytokine signaling pathway after diffuse traumatic brain injury (TBI) in ovariectomized rats. Methods: Female rats were divided into 10 groups: control, sham, TBI, Vehicle (oil), Vehicle E1 (33.3 mu g/kg), E2 (1 mg / kg), P1 (1.7 mg/kg), P2 (8 mg / kg), E2 + P1. All drugs were injected 0.5 h after TBI. Brain edema and the brain levels of P-STAT-3, NF kappa B-P52, NF kappa B-P65, P-I kappa B, and SOCS-3 by immunohistochemistry measured at 24 h after TBI. Results: Increased brain edema after TBI was inhibited by different doses of estrogen, progesterone (P < 0.001), and E2 + P1 (P < 0.05). The brain levels of P-STAT-3, NF kappa B-P52, NF kappa B-P65, and p-I kappa B alpha that increased after TBI was decreased only by E2 (P < 0.05). E2 and E2 + P1 have increased the SOCS-3 level after TBI (P < 0.05). Also, there was a difference between the E2 with E1 and two progesterone doses (P < 0.05). So that in all cases, the effects of E2 were more significant than the other groups. The target cells for these effects of E2 were microglia and astrocytes. Conclusion: The results indicate that one of the probable mechanism(s) of estrogen anti-inflammatory effect after TBI is either reduction of p-STAT-3, NF kappa B-P52, p-NF kappa B-P65, and p-I kappa B alpha or increase in SOCS-3 molecules involved in the signaling pathway of inflammatory cytokines.

Automated summary

The aim of this study was to determine the anti-inflammatory effect of female sex hormones on the level of intracellular molecules of cytokine signaling pathway after diffuse traumatic brain injury (TBI) in ovariectomized rats. The results showed that female sex hormones can inhibit the increase of brain edema, decrease the levels of inflammatory factors, and increase the levels of molecules involved in the signaling pathway of inflammation. These effects primarily act on microglia and astrocytes.