title: Effects of fumaric acids on cuprizone induced central nervous system de- and remyelination in the mouse.
abstract: BACKGROUND
  Fumaric acid esters (FAE) are a group of compounds which are currently under investigation as an oral treatment for relapsing-remitting multiple sclerosis. One of the suggested modes of action is the potential of FAE to exert a neuroprotective effect.
  
  
  RESULTS
  We have investigated the impact of monomethylfumarate (MMF) and dimethylfumaric acid (DMF) on de- and remyelination using the toxic cuprizone model where the blood-brain-barrier remains intact and only scattered T-cells and peripheral macrophages are found in the central nervous system (CNS), thus excluding the influence of immunomodulatory effects on peripheral immune cells. FAE showed marginally accelerated remyelination in the corpus callosum compared to controls. However, we found no differences for demyelination and glial reactions in vivo and no cytoprotective effect on oligodendroglial cells in vitro. In contrast, DMF had a significant inhibitory effect on lipopolysaccharide (LPS) induced nitric oxide burst in microglia and induced apoptosis in peripheral blood mononuclear cells (PBMC).
  
  
  CONCLUSIONS
  These results contribute to the understanding of the mechanism of action of fumaric acids. Our data suggest that fumarates have no or only little direct protective effects on oligodendrocytes in this toxic model and may act rather indirectly via the modulation of immune cells.
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Darius
authors.initials: D
authors.lastname: Moharregh-Khiabani
authors.forename: Alexander
authors.initials: A
authors.lastname: Blank
authors.forename: Thomas
authors.initials: T
authors.lastname: Skripuletz
authors.forename: Elvira
authors.initials: E
authors.lastname: Miller
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kotsiari
authors.forename: Viktoria
authors.initials: V
authors.lastname: Gudi
authors.forename: Martin
authors.initials: M
authors.lastname: Stangel
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism*; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000188:drug therapy*; D000069462:Dimethyl Fumarate; D005650:Fumarates / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008297:Male; D008298:Maleates / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005650:Fumarates; D008298:Maleates; C073341:citraconic acid; D003471:Cuprizone; D000069462:Dimethyl Fumarate