Axonal protection achieved in a model of multiple sclerosis using lamotrigine

David A. Bechtold, Sandra J. Miller, Angela C. Dawson, Yue Sun, Raju Kapoor, David Berry, Kenneth J. Smith

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    Axonal degeneration is a major cause of permanent disability in multiple sclerosis (MS). Recent observations from our and other laboratories suggest that sodium accumulation within compromised axons is a key, early step in the degenerative process, and hence that limiting axonal sodium influx may represent a mechanism for axonal protection in MS. Here we assess whether lamotrigine, a sodium channel-blocking agent, is effective in preventing axonal degeneration in an animal model of MS, namely chronic-relapsing experimental autoimmune encephalomyelitis (CR-EAE). When administered from 7 days post-inoculation, lamotrigine provided a small but significant reduction in the neurological deficit present at the termination of the experiments (averaged over three independent experiments; vehicle: 3.5 ± 2.7; lamotrigine: 2.6 ± 2.0, P <0.05) and preserved more functional axons in the spinal cord (measured as mean compound action potential area; vehicle: 31.7 μ ± 23.0; lamotrigine: 42.9 ± 27.4, P <0.05). Histological examination of the thoracic spinal cord (n = 71) revealed that lamotrigine treatment also provided significant protection against axonal degeneration (percentage degeneration in dorsal column; vehicle: 33.5 % ± 38.5; lamotrigine: 10.4 % ± 12.5, P <0.01). The findings suggest that lamotrigine may provide a novel avenue for axonal protection in MS. © 2006 Steinkopff Verlag.
    Original languageEnglish
    Pages (from-to)1542-1551
    Number of pages9
    JournalJournal of Neurology
    Issue number12
    Publication statusPublished - Dec 2006


    • Axonal loss
    • Degeneration
    • EAE
    • Sodium channel


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