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 in vitro. To determine whether phenytoin has a protective effect on axons in a neuroinflammatory model in vivo, we studied the effect of phenytoin on axonal degeneration in the optic nerve in MOG-induced experimental allergic encephalomyelitis (EAE). We report that, whereas ∼50% of optic nerve axons are lost at 27–28 days in untreated EAE, only ∼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.