title: Neuroprotective effects of progesterone in chronic experimental autoimmune encephalomyelitis.
abstract: Observations so far obtained in experimental autoimmune encephalomyelitis (EAE) have revealed the promising neuroprotective effects exerted by progesterone (PROG). The findings suggest that this neuroactive steroid may potentially represent a therapeutic tool for multiple sclerosis (MS). However, up to now, the efficacy of PROG has been only tested in the acute phase of the disease, whereas it is well known that MS expresses different features depending on the phase of the disease. Accordingly, we have evaluated the effect of PROG treatment in EAE induced in Dark Agouti rats (i.e. an experimental model showing a protracted relapsing EAE). Data obtained 45 days after EAE induction show that PROG treatment exerts a beneficial effect on clinical score, confirming surrogate parameters of spinal cord damage in chronic EAE (i.e. reactive microglia, cytokine levels, activity of the Na(+) ,K(+) -ATPase pump and myelin basic protein expression). An increase of the levels of dihydroprogesterone and isopregnanolone (i.e. two PROG metabolites) was also observed in the spinal cord after PROG treatment. Taken together, these results indicate that PROG is effective in reducing the severity of chronic EAE and, consequently, may have potential with respect to MS treatment.
authors.affiliation: Department of Endocrinology, Pathophysiology and Applied Biology, Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano, Milano, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Giatti
authors.forename: D
authors.initials: D
authors.lastname: Caruso
authors.forename: M
authors.initials: M
authors.lastname: Boraso
authors.forename: F
authors.initials: F
authors.lastname: Abbiati
authors.forename: E
authors.initials: E
authors.lastname: Ballarini
authors.forename: D
authors.initials: D
authors.lastname: Calabrese
authors.forename: M
authors.initials: M
authors.lastname: Pesaresi
authors.forename: R
authors.initials: R
authors.lastname: Rigolio
authors.forename: M
authors.initials: M
authors.lastname: Santos-Galindo
authors.forename: B
authors.initials: B
authors.lastname: Viviani
authors.forename: G
authors.initials: G
authors.lastname: Cavaletti
authors.forename: L M
authors.initials: LM
authors.lastname: Garcia-Segura
authors.forename: R C
authors.initials: RC
authors.lastname: Melcangi
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects*
chemical_list: D018696:Neuroprotective Agents; D011374:Progesterone