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


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.


Axonal loss degeneration EAE sodium channel 



We would like to thank Mr. Meirion Davies, Ms. Clare Farmer, Mr. Matthew Smith and Dr. Marija Sajic for technical assistance relating to this work. Lamotrigine was kindly provided by GlaxoSmithKline. The work was supported by grants from the Multiple Sclerosis Society of Great Britain and Northern Ireland, a PhD studentship (to DAB) from King’s College, and a bursary (to ACD) from the Health Foundation.


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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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