Dimethyl Fumarate Ameliorates Lewis Rat Experimental Autoimmune Neuritis and Mediates Axonal Protection

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 L...

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Bibliographic Details
Published in:PloS one 2015-11, Vol.10 (11), p.e0143416-e0143416
Main Authors: Pitarokoili, Kalliopi, Ambrosius, Björn, Meyer, Daniela, Schrewe, Lisa, Gold, Ralf
Format: Article
Language:English
Subjects:
Amino acids
Animals
Antigens
Apoptosis
Axons - drug effects
Cytokines
Dimethyl Fumarate - administration & dosage
Dimethyl Fumarate - pharmacology
Dimethyl Fumarate - therapeutic use
Drinking water
Electrodes
Female
Guillain-Barre syndrome
Histology
Immunization
Medical innovations
Multiple sclerosis
Nervous system
Neuritis, Autoimmune, Experimental - drug therapy
Neurology
Neuroprotective Agents - administration & dosage
Neuroprotective Agents - pharmacology
Neuroprotective Agents - therapeutic use
Neurosciences
Peripheral neuropathy
Psoriasis
Rats
Rats, Inbred Lew
Rodents
Schwann Cells - drug effects
Studies
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Summary: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. 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. We conclude that immunomodulatory and neuroprotective dimethyl fumarate may represent an innovative therapeutic option in human autoimmune neuropathies.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0143416