Abstract | BACKGROUND: METHODS AND FINDINGS:
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 | Kalliopi Pitarokoili, Björn Ambrosius, Daniela Meyer, Lisa Schrewe, Ralf Gold |
Journal | PloS one
(PLoS One)
Vol. 10
Issue 11
Pg. e0143416
( 2015)
ISSN: 1932-6203 [Electronic] United States |
PMID | 26618510
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Neuroprotective Agents
- Dimethyl Fumarate
|
Topics |
- Animals
- Axons
(drug effects)
- Dimethyl Fumarate
(administration & dosage, pharmacology, therapeutic use)
- Female
- Neuritis, Autoimmune, Experimental
(drug therapy)
- Neuroprotective Agents
(administration & dosage, pharmacology, therapeutic use)
- Rats
- Rats, Inbred Lew
- Schwann Cells
(drug effects)
|