Effect of estrogen and/or progesterone administration on traumatic brain injury-caused brain edema: the changes of aquap
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ORIGINAL PAPER
Effect of estrogen and/or progesterone administration on traumatic brain injury-caused brain edema: the changes of aquaporin-4 and interleukin-6 Zahra Soltani & Mohammad Khaksari & Nader Shahrokhi & Gholamabbas Mohammadi & Behshad Mofid & Ali Vaziri & Sedigheh Amiresmaili Received: 31 October 2014 / Accepted: 24 November 2015 # University of Navarra 2015
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 Z. Soltani : N. Shahrokhi Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran M. Khaksari (*) Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran e-mail: [email protected] G. Mohammadi : A. Vaziri Department of Biochemistry, Medical School of Afzalipour, Kerman University of Medical Sciences, Kerman, Iran B. Mofid Department of Neurosurgery, Shahid Bahonar Hospital of Kerman, Kerman, Iran S. Amiresmaili Bam University of Medical Sciences, Kerman, Iran
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. Keywords Interleukin-6 . Aquaporin-4 . Traumatic brain injury . Estrogen . Progesterone Abbreviations AQP4 Aquaporin-4 IL-6 Interleukin-6 TBI Traumatic brain injury E1 Low dose of estrogen P1 Low dose of progesterone E2 High dose of estrogen P2 High dose of progesterone AQPs Aquaporins IL-1β Interleukin-1β NFκB Nuclear factor kappa b OVX Ovariectomized T-PER Tissue protein extraction reagent ELISA Enzyme-linked immunosorbent assay RT-PCR Reverse transcription-polymerase chain reaction
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Introduction In defin
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