Vitamin D deficiency reduces the benefits of progesterone treatment after brain injury in aged rats

• Type of Material: Article
• Authors: Milos Cekic, Emory University; Sarah M. Cutler, Emory University; Jacob W. VanLandingham, Emory University; Donald G Stein, Emory University
• Language: English
• Date: 2011-05
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2009 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.neurobiolaging.2009.04.017
• Title of Journal or Parent Work: Neurobiology of Aging
• ISSN: 0197-4580
• Volume: 32
• Issue: 5
• Start Page: 864
• End Page: 874
• Grant/Funding Information: This research was supported by funding from NIH grants #1RO1N540825 and #1RO1N538664 and the Emory University Graduate School of Arts and Sciences.
• Keywords: 1,25-Dihydroxyvitamin D3; Progesterone; Aging; Vitamin D deficiency; Traumatic brain injury; Inflammation
• Research Categories: Biology, Neuroscience; Health Sciences, Nutrition; Health Sciences, General

Abstract

Administration of the neurosteroid progesterone (PROG) has been shown to be beneficial in a number of brain injury models and in two recent clinical trials. Given widespread vitamin D deficiency and increasing traumatic brain injuries (TBIs) in the elderly, we investigated the interaction of vitamin D deficiency and PROG with cortical contusion injury in aged rats. Vitamin D deficient (VitD-deficient) animals showed elevated inflammatory proteins (TNFα, IL-1β, IL-6, NFκB p65) in the brain even without injury. VitD-deficient rats with TBI, whether given PROG or vehicle, showed increased inflammation and greater open-field behavioral deficits compared to VitD-normal animals. Although PROG was beneficial in injured VitD-normal animals, in VitD-deficient subjects neurosteroid treatment conferred no improvement over vehicle. A supplemental dose of 1,25-dihydroxyvitamin D3 (VDH) given with the first PROG treatment dramatically improved results in VitD-deficient rats, but treatment with VDH alone did not. Our results suggest that VitD-deficiency can increase baseline brain inflammation, exacerbate the effects of TBI, and attenuate the benefits of PROG treatment; these effects may be reversed if the deficiency is corrected.