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Author Notes:

Address for correspondence: Donald G. Stein, Ph.D., Emory University, 1365 B Clifton Rd NE, Suite 5100, Atlanta GA 30322 USA, 404 712 2540 voice, 404 727 2388 fax, dstei04@emory.edu.

Corresponding author at: Emory University, 1365 B Clifton Rd NE, Suite 5100, Atlanta, GA 30322, USA. Fax: + 1 404 727 2388.

The authors would like to thank Leslie McCann for the invaluable editorial assistance and Jason S. Lee and Kristen Carroll for their contribution to the paper.

Disclosure DG Stein is party to a licensing agreement with BHR Pharmaceuticals, Ltd. related to PROG usage in TBI. This agreement has been approved by Emory University, who receives the largest share of fees in accordance with its conflict of interest policies. DGS also serves as consultant to BHR and may receive royalties and research funding from BHR occasionally.


Research Funding:

This work was supported by NIH grant 1R01HD061971 to DGS.


  • Aging
  • Combination treatments
  • Functional repair
  • Progesterone
  • Traumatic brain injury
  • Vitamin D deficiency
  • Vitamin D3 hormone

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


Journal Title:

Hormones and Behavior


Volume 64, Number 3


Type of Work:

Article | Post-print: After Peer Review


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.

Copyright information:

© 2013 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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