Combination treatment with progesterone and vitamin D hormone may be more effective than monotherapy for nervous system injury and disease

被引:84
作者
Cekic, Milos [1 ]
Sayeed, Iqbal [1 ]
Stein, Donald G. [1 ]
机构
[1] Emory Univ, Dept Emergency Med, Sch Med, Emergency Med Brain Res Lab, Atlanta, GA 30322 USA
关键词
1,25-Dihydroxyvitamin D-3; Combination therapy; Neurosteroids; Progesterone; Traumatic brain injury; Vitamin D; TRAUMATIC BRAIN-INJURY; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ACTIVATED PROTEIN-KINASE; NITRIC-OXIDE SYNTHASE; 1,25-DIHYDROXYVITAMIN-D3 RECEPTOR IMMUNOREACTIVITY; KAPPA-B ACTIVATION; GROWTH-FACTOR; D DEFICIENCY; CELL-CYCLE; GENE-EXPRESSION;
D O I
10.1016/j.yfrne.2009.04.002
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
More than two decades of pre-clinical research and two recent clinical trials have shown that progesterone (PROG) and its metabolites exert beneficial effects after traumatic brain injury (TBI) through a number of metabolic and physiological pathways that can reduce damage in many different tissues and organ systems. Emerging data on 1,25-dihydroxyvitamin D-3 (VDH), itself a steroid hormone, have begun to provide evidence that, like PROG, it too is neuroprotective, although some of its actions may involve different pathways. Both agents have high safety profiles, act on many different injury and pathological mechanisms, and are clinically relevant, easy to administer, and inexpensive. Furthermore, vitamin D deficiency is prevalent in a large segment of the population, especially the elderly and institutionalized, and can significantly affect recovery after CNS injury. The combination of PROG and VDH in pre-clinical and clinical studies is a novel and compelling approach to TBI treatment. (C) 2009 Elsevier Inc. All rights reserved.
引用
收藏
页码:158 / 172
页数:15
相关论文
共 315 条
[81]   Vitamin D and the vitamin D receptor are critical for control of the innate immune response to colonic injury [J].
Froicu, Monica ;
Cantorna, Margherita T. .
BMC IMMUNOLOGY, 2007, 8 (1)
[82]   STUDIES ON THE CELLULAR-LOCALIZATION AND DISTRIBUTION OF GLUCOCORTICOID RECEPTOR AND ESTROGEN-RECEPTOR IMMUNOREACTIVITY IN THE CENTRAL NERVOUS-SYSTEM OF THE RAT AND THEIR RELATIONSHIP TO THE MONOAMINERGIC AND PEPTIDERGIC NEURONS OF THE BRAIN [J].
FUXE, K ;
CINTRA, A ;
AGNATI, LF ;
HARFSTRAND, A ;
WIKSTROM, AC ;
OKRET, S ;
ZOLI, M ;
MILLER, LS ;
GREENE, JL ;
GUSTAFSSON, JA .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1987, 27 (1-3) :159-170
[83]   Steroid protection in the experimental autoimmune encephalomyelitis model of multiple sclerosis [J].
Garay, Laura ;
Deniselle, Maria Claudia Gonzalez ;
Gierman, Lobke ;
Meyer, Maria ;
Lima, Analia ;
Roig, Paulina ;
De Nicola, Alejandro F. .
NEUROIMMUNOMODULATION, 2008, 15 (01) :76-83
[84]   Estradiol upregulates Bcl-2 expression in adult brain neurons [J].
Garcia-Segura, LM ;
Cardona-Gomez, P ;
Naftolin, F ;
Chowen, JA .
NEUROREPORT, 1998, 9 (04) :593-597
[85]   1,25-dihydroxyvitamin D3 regulates the synthesis of γ-glutamyl transpeptidase and glutathione levels in rat primary astrocytes [J].
Garcion, E ;
Sindji, L ;
Leblondel, G ;
Brachet, P ;
Darcy, F .
JOURNAL OF NEUROCHEMISTRY, 1999, 73 (02) :859-866
[86]   New clues about vitamin D functions in the nervous system [J].
Garcion, E ;
Wion-Barbot, N ;
Montero-Menei, CN ;
Berger, F ;
Wion, D .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2002, 13 (03) :100-105
[87]   Treatment of experimental autoimmune encephalomyelitis in rat by 1,25-dihydroxyvitamin D3 leads to early effects within the central nervous system [J].
Garcion, E ;
Sindji, L ;
Nataf, S ;
Brachet, P ;
Darcy, F ;
Montero-Menei, CN .
ACTA NEUROPATHOLOGICA, 2003, 105 (05) :438-448
[88]   1,25-Dihydroxyvitamin D-3 inhibits the expression of inducible nitric oxide synthase in rat central nervous system during experimental allergic encephalomyelitis [J].
Garcion, E ;
Nataf, S ;
Berod, A ;
Darcy, F ;
Brachet, P .
MOLECULAR BRAIN RESEARCH, 1997, 45 (02) :255-267
[89]  
Garcion E, 1998, GLIA, V22, P282, DOI 10.1002/(SICI)1098-1136(199803)22:3<282::AID-GLIA7>3.0.CO
[90]  
2-7