Neuroprotection of axons with phenytoin in experimental allergic encephalomyelitis.
Voltage-gated sodium channels contribute to the development of axonal degeneration in white matter, and sodium channel blocking drugs are known to have a protective effect on acutely injured white matter axons. To determine whether phenytoin has a protective effect on axons in a neuroinflammatory model, we studied the effect of phenytoin on axonal degeneration in the optic nerve in MOG-induced experimental allergic encephalomyelitis (EAE). We report that, whereas approximately 50% of optic nerve axons are lost at 27-28 days in untreated EAE, only approximately 12% of the axons are lost if mice with MOG-induced EAE are treated with phenytoin. These results demonstrate that it is possible to achieve substantial protection of white matter axons in EAE, a model neuroinflammatory/demyelination disease, with a sodium channel blocking agent.
Lo
Albert C
AC
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Black
Joel A
JA
Waxman
Stephen G
SG
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D004676:Myelin Basic Protein / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016900:Neurofilament Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009900:Optic Nerve / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010672:Phenytoin / Q000494:pharmacology* / Q000627:therapeutic use; D026941:Sodium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome
D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; D018696:Neuroprotective Agents; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D010672:Phenytoin