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

Abstract

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 µg/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, NFκB-P52, NFκB-P65, P-IκB, 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, NFκB-P52, NFκB-P65, and p-IκBα 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, NFκB-P52, p-NFκB-P65, and p-IκBα or increase in SOCS-3 molecules involved in the signaling pathway of inflammatory cytokines.

Keywords: Brain edema; Female sex steroids; NFκB-P52; P-IκBα; P-NFκB-P65; P-STAT-3; SOCS-3; Traumatic brain injury.