Skip Navigation



Brain Advance Access published online on August 24, 2006
Brain, doi:10.1093/brain/awl216
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
129/12/3196    most recent
awl216v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Black, J. A.
Right arrow Articles by Waxman, S. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Black, J. A.
Right arrow Articles by Waxman, S. G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author (2006). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received March 22, 2006
Revised July 7, 2006
Accepted July 19, 2006

Article

Long-term protection of central axons with phenytoin in monophasic and chronic-relapsing EAE

Joel A. Black 1 *, Shujun Liu 1, Bryan C. Hains 1, Carl Y. Saab 2, and Stephen G. Waxman 1

1 Department of Neurology and Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT, USA; Rehabilitation Research Center, VA Connecticut Healthcare System, West Haven, CT, USA
2 Department of Surgery, Brown University School of Medicine, Providence, RI, USA

* To whom correspondence should be addressed.
Joel A. Black, E-mail: joel.black{at}yale.edu


  Abstract

Axonal degeneration is a major contributor to non-remitting deficits in multiple sclerosis, and there is thus considerable current interest in the development of strategies that might prevent axonal loss in neuroinflammatory disease. Dysregulation of sodium ion homeostasis has been implicated in mechanisms leading to axonal degeneration, and several studies have shown that blockade of sodium channels can ameliorate axon damage following anoxic, traumatic and nitric oxide-induced CNS injury. Two sodium channel blockers, phenytoin and flecainide, have been reported to protect axons in experimental autoimmune encephalomyelitis (EAE) for 30 days, but long-term protective effects have not been studied. We demonstrate here that oral administration of phenytoin provides long-term (up to 180 days) protection for spinal cord corticospinal tract (CST) and dorsal column (DC) axons in both monophasic (C57/BL6 mice) and chronic-relapsing (Biozzi mice) murine EAE. Untreated C57/BL6 mice exhibit a 40-50% loss of CST and DF axons at 90 and 180 days post-EAE induction via myelin-oligodendrocyte glycoprotein (MOG) injection. In contrast, only 4% of DF axons are lost at 90 days, and only 8% are lost at 180 days in phenytoin-treated C57/BL6 mice with EAE; only 21-29% of CST axons are lost at 90 and 180 days in phenytoin-treated C57/BL6 mice with EAE. Attenuation of dorsal column compound action potentials was ameliorated and clinical status was also significantly enhanced with phenytoin treatment at 90 and 180 days in this model. In addition, inflammatory cell infiltration into the dorsal columns was reduced in phenytoin-treated mice with EAE compared with untreated mice with EAE. Similar results were obtained in Biozzi mice with chronic-relapsing EAE followed for 120 days post-injection. These observations demonstrate that phenytoin provides long-term protection of CNS axons and improves clinical status in both monophasic and chronic-relapsing models of neuroinflammation.

Keywords: axon protection; EAE; inflammatory cell; multiple sclerosis; phenytoin; sodium channel.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 JDRHome page
A.M.M. Suzuki, A. Yoshimura, Y. Ozaki, T. Kaneko, and Y. Hara
Cyclosporin A and Phenytoin Modulate Inflammatory Responses
Journal of Dental Research, December 1, 2009; 88(12): 1131 - 1136.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
A. M. Soulika, E. Lee, E. McCauley, L. Miers, P. Bannerman, and D. Pleasure
Initiation and Progression of Axonopathy in Experimental Autoimmune Encephalomyelitis
J. Neurosci., November 25, 2009; 29(47): 14965 - 14979.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. B. Sattler, S. K. Williams, C. Neusch, M. Otto, J. R. Pehlke, M. Bahr, and R. Diem
Flupirtine as Neuroprotective Add-On Therapy in Autoimmune Optic Neuritis
Am. J. Pathol., November 1, 2008; 173(5): 1496 - 1507.
[Abstract] [Full Text] [PDF]

Home page
 Mult SclerHome page
A Wilkins and N Scolding
Protecting axons in multiple sclerosis
Multiple Sclerosis, September 1, 2008; 14(8): 1013 - 1025.
[Abstract] [PDF]

Home page
 Mult SclerHome page
R.E. Gonsette
Review: Oxidative stress and excitotoxicity: a therapeutic issue in multiple sclerosis?
Multiple Sclerosis, January 1, 2008; 14(1): 22 - 34.
[Abstract] [PDF]

Home page
 BrainHome page
K. J. Smith
Axonal protection in multiple sclerosis--a particular need during remyelination?
Brain, December 1, 2006; 129(12): 3147 - 3149.
[Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.