Journal of Neurology

, Volume 253, Issue 12, pp 1542–1551 | Cite as

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
ORIGINAL COMMUNICATION

Abstract

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 μV.ms ± 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.

Keywords

Axonal loss degeneration EAE sodium channel 

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Copyright information

© Steinkopff Verlag Darmstadt 2006

Authors and Affiliations

  • David A. Bechtold
    • 1
  • Sandra J. Miller
    • 1
  • Angela C. Dawson
    • 1
  • Yue Sun
    • 1
  • Raju Kapoor
    • 1
    • 2
  • David Berry
    • 3
  • Kenneth J. Smith
    • 1
  1. 1.Dept. of Clinical NeuroscienceKing’s College LondonLondonUK
  2. 2.National Hospital for Neurology and NeurosurgeryLondonUK
  3. 3.Medical Toxicology UnitGuy’s and St Thomas’ TrustLondonUK

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