Vitamin D deficiency reduces the benefits of progesterone treatment after brain injury in aged rats.
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 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.
Cekic
Milos
M
Department of Emergency Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Cutler
Sarah M
SM
VanLandingham
Jacob W
JW
Stein
Donald G
DG
D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D011374:Progesterone / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D014808:Vitamin D Deficiency / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology
D016207:Cytokines; D011374:Progesterone