Progesterone and vitamin D: Improvement after traumatic brain injury in middle-aged rats

• Type of Material: Article
• Authors: Huiling Tang, Emory University; Fang Hua, Emory University; Jun Wang, Emory University; Iqbal Sayeed, Emory University; Xiaojing Wang, Emory University; Zhengjia Chen, Emory University; Seema Yousuf, Emory University; Fahim Atif, Emory University; Donald G Stein, Emory University
• Language: English
• Date: 2013-08
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 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.yhbeh.2013.06.009
• Title of Journal or Parent Work: Hormones and Behavior
• ISSN: 0018-506X
• Volume: 64
• Issue: 3
• Grant/Funding Information: This work was supported by NIH grant 1R01HD061971 to DGS.
• Keywords: Progesterone; Combination treatments; Vitamin D deficiency; Functional repair; Traumatic brain injury; Vitamin D3 hormone; Aging
• Research Categories: Health Sciences, Human Development; Health Sciences, Medicine and Surgery; Biology, Biostatistics

Abstract

Progesterone (PROG) and vitamin D hormone (VDH) have both shown promise in treating traumatic brain injury (TBI). Both modulate apoptosis, inflammation, oxidative stress, and excitotoxicity. We investigated whether 21 days of VDH deficiency would alter cognitive behavior after TBI and whether combined PROG and VDH would improve behavioral and morphological outcomes more than either hormone alone in VDH-deficient middle-aged rats given bilateral contusions of the medial frontal cortex. PROG (16 mg/kg) and VDH (5 µg/kg) were injected intraperitoneally 1 hour post-injury. Eight additional doses of PROG were injected subcutaneously over 7 days post-injury. VDH deficiency itself did not significantly reduce baseline behavioral functions or aggravate impaired cognitive outcomes. Combination therapy showed moderate improvement in preserving spatial and reference memory but was not significantly better than PROG monotherapy. However, combination therapy significantly reduced neuronal loss and the proliferation of reactive astrocytes, and showed better efficacy compared to VDH or PROG alone in preventing MAP-2 degradation. VDH+PROG combination therapy may attenuate some of the potential long-term, subtle, pathophysiological consequences of brain injury in older subjects.