Effect of estrogen and/or progesterone administration on traumatic brain injury-caused brain edema: the changes of aquaporin-4 and interleukin-6

Abstract The role of aquaporin-4 (AQP4) and interleukin-6 (IL-6) in the development of brain edema post-traumatic brain injury (TBI) has been indicated. The present study was designed to investigate the effect( s) of administration of progesterone (P) and/or estrogen (E) on brain water content, AQP4 expression, and IL-6 levels post-TBI. The ovariectomized rats were divided into 11 groups: sham, one vehicle, two vehicles, E1, E2, P1, P2, E1 + P1, E1 + P2, E2 + P1, and E2 + P2. The brain AQP4 expression, IL-6 levels, and water content were evaluated 24 h after TBI induced by Marmarou’s method. The low (E1 and P1) and high (E2 and P2) doses of estrogen and progesterone were administered 30 min post-TBI. The results showed that brain water content and AQP4 expression decreased in the E1, E2, P1, and P2-treated groups. The administration of E1 decreased IL-6 levels. Addition of progesterone decreased the inhibitory effect of E1 and E2 on the accumulation of water in the brain.Administration of E1 + P1 and E1 + P2 decreased the inhibitory effect of E1 on the IL-6 levels and AQP4 protein expression. Our findings suggest that estrogen or progesterone by itself has more effective roles in decrease of brain edema than combination of both. Possible mechanism may be mediated by the alteration of AQP4 and IL-6 expression. However, further studies are required to verify the exact mechanism

What are the progesterone-induced changes of the outcome and the serum markers of injury, oxidant activity and inflammation in diffuse axonal injury patients?

To permit appropriate targeted therapy, the present clinical studywas aimed to investigate the effects of progesterone on the outcome and the serum markers of injury, oxidant activity and inflammation in diffuse axonal injury (DAI). Forty-eightmaleDAI patients were divided into two groups (control and progesterone). Progesterone group received progesterone in dose of 1 mg/kg per 12 h for five days. The outcome was investigated using Extended Glasgow Outcome Scale (GOS-E) and functional independencemeasure (FIM). Themarkers of inflammation [interleukin-1β (IL-1β), IL-6, transforming growth factor-β1 (TGF-β1)], injury (brain protein of S-100B), and oxidant activity [malondialdehyde (MDA)] were evaluated in the serum of the patients. Higher GOS-E and FIMscoreswere observed in progesterone group at the six-month follow-up (P b 0.05 and P b 0.01, respectively). Meanwhile, a reduction in the serum levels of IL-1β, MDA and S-100B was noticed in progesterone group 24 h after injury (P b 0.05, P b 0.001 and P b 0.05, respectively), and there was an increase in serum levels of IL-6 and TGF-β1 (P b 0.01 and P b 0.05, respectively). Also, lower levels of MDA and S-100B, and higher levels of TGF-β1were observed in progesterone group six days after injury (P b 0.05). According to these findings, progesterone may improve the outcome in DAI patients probably through modulation in the levels of cytokines, and reduction in the injury and oxidant activity