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

NEUROBIOLOGY OF AGING

卷:32

Article

Stein, Donald G.¹ 

[1] Emory Clin, Emergency Med Brain Res Lab, Sch Med, Dept Emergency Med, Atlanta, GA 30322 USA

关键词: Aging;    Inflammation;    Progesterone;    1,25-Dihydroxyvitamin D-3;    Traumatic brain injury;    Vitamin D deficiency;   

DOI  :  10.1016/j.neurobiolaging.2009.04.017

来源: Elsevier

【 摘 要 】

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 (TNF alpha, IL-1 beta, IL-6, NF kappa B 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 D-3 (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. (C) 2009 Elsevier Inc. All rights reserved.

【 授权许可】

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