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

• Published in: Neurobiology of aging Vol. 32; no. 5; pp. 864 - 874
• Main Authors: Cekic, Milos, Cutler, Sarah M., VanLandingham, Jacob W., Stein, Donald G.
• Format: Journal Article
• Language: English
• Published: London Elsevier Inc 01.05.2011; Elsevier
• Subjects: 1,25-Dihydroxyvitamin D 3; Aging; Aging - drug effects; Aging - metabolism; Animals; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Brain Injuries - drug therapy; Brain Injuries - metabolism; Cytokines - metabolism; Development. Senescence. Regeneration. Transplantation; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Inflammation; Injuries of the nervous system and the skull. Diseases due to physical agents; Internal Medicine; Male; Medical sciences; Neurology; Progesterone; Progesterone - therapeutic use; Rats; Rats, Inbred F344; Traumas. Diseases due to physical agents; Traumatic brain injury; Vertebrates: nervous system and sense organs; Vitamin D deficiency; Vitamin D Deficiency - drug therapy; Vitamin D Deficiency - metabolism; Vitamin D Deficiency - physiopathology; Aging; Vitamin D deficiency; Inflammation; 1,25-Dihydroxyvitamin D 3; Traumatic brain injury; Progesterone; Senescence; Rat; Steroid hormone; Cholecalciferol(1,25-dihydroxy); Rodentia; Central nervous system; Trauma; Ovarian hormone; Encephalon; Micronutrient; Vertebrata; Mammalia; Vitamin D; Animal; 1,25-Dihydroxyvitamin D; Lesion; Sex steroid hormone
• ISSN: 0197-4580; 1558-1497; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2009.04.017

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.