title: Dimethyl Fumarate Ameliorates Lewis Rat Experimental Autoimmune Neuritis and Mediates Axonal Protection.
abstract: BACKGROUND
  Dimethyl fumarate is an immunomodulatory and neuroprotective drug, approved recently for the treatment of relapsing-remitting multiple sclerosis. In view of the limited therapeutic options for human acute and chronic polyneuritis, we used the animal model of experimental autoimmune neuritis in the Lewis rat to study the effects of dimethyl fumarate on autoimmune inflammation and neuroprotection in the peripheral nervous system.
  
  
  RESULTS
  Experimental autoimmune neuritis was induced by immunization with the neuritogenic peptide (amino acids 53-78) of P2 myelin protein. Preventive treatment with dimethyl fumarate given at 45 mg/kg twice daily by oral gavage significantly ameliorated clinical neuritis by reducing demyelination and axonal degeneration in the nerve conduction studies. Histology revealed a significantly lower degree of inflammatory infiltrates in the sciatic nerves. In addition, we detected a reduction of early signs of axonal degeneration through a reduction of amyloid precursor protein expressed in axons of the peripheral nerves. This reduction correlated with an increase of nuclear factor (erythroid derived 2)-related factor 2 positive axons, supporting the neuroprotective potential of dimethyl fumarate. Furthermore, nuclear factor (erythroid derived 2)-related factor 2 expression in Schwann cells was only rarely detected and there was no increase of Schwann cells death during EAN.
  
  
  CONCLUSIONS
  We conclude that immunomodulatory and neuroprotective dimethyl fumarate may represent an innovative therapeutic option in human autoimmune neuropathies.
authors.affiliation: Department of Neurology, St. Josef Hospital, Ruhr- University of Bochum, Bochum, Germany.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Pitarokoili
authors.affiliation: Department of Neurology, St. Josef Hospital, Ruhr- University of Bochum, Bochum, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Ambrosius
authors.affiliation: Department of Neurology, St. Josef Hospital, Ruhr- University of Bochum, Bochum, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Meyer
authors.affiliation: Department of Neurology, St. Josef Hospital, Ruhr- University of Bochum, Bochum, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Schrewe
authors.affiliation: Department of Neurology, St. Josef Hospital, Ruhr- University of Bochum, Bochum, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects*; D000069462:Dimethyl Fumarate / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D012583:Schwann Cells / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D000069462:Dimethyl Fumarate