Steroid Protection in the Experimental Autoimmune Encephalomyelitis Modelo of Multiple Sclerosis

GARAY L; GONZALEZ DENISELLE MC; GIERMAN L; MEYER, M; LIMA A; ROIG P; DE NICOLA A.F

NEUROIMMUNOMODULATION.

Karger

Año: 2008 vol. 15 p. 76 - 83

1021-7401

Objectives: Based on evidence that pregnant women with  multiple sclerosis (MS) show a decline in the relapse rate during the third trimester and an increase during the first 3 months postpartum, the suggestion was made that high levels of circulating sex steroids are responsible for pregnancymediated  neuroprotection. As both estradiol (E 2 ) and progesterone exert neuroprotective and myelinating effects on the nervous system, the effects of sex steroids were studied in the experimental autoimmune encephalomyelitis (EAE) model of MS. Methods: EAE was induced in female C57BL/6 mice by administration of a myelin oligodendrocyte protein (MOG 40?45 ) peptide. Clinical signs of EAE, myelin protein expression  and neuronal parameters were determined in mice with or without hormonal treatment. Results: Progesterone given prior to EAE induction attenuated the clinical scores of the disease, slightly delayed disease onset and decreased demyelination foci, according to luxol fast blue staining (LFB), myelin basic protein (MBP) and proteolipid protein (PLP) and mRNA expression. Motoneuron expression of Na,K-ATPase mRNA was also enhanced by progesterone. In turn, combined E 2 plus progesterone therapy more effectively prevented neurological deficits, fully restored LFB staining, MBP and PLP immunoreactivity and avoided inflammatory cell infiltration. On the neuronal side, steroid biotherapy increased brain-derived neurotrophic factor (BDNF) mRNA. Conclusion: Early treatment with progesterone alone or more evidently in combination with E 2 showed a clinical benefit and produced myelinating and neuroprotective effects in mice with MOG 40?45 -induced EAE. Therefore, sex steroids should be considered as potential novel therapeutic strategies for MS.