Linked Life Data

12904334

Source:http://linkedlifedata.com/resource/pubmed/id/12904334

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2003-11-17
pubmed:abstractText
Axonal degeneration within the spinal cord contributes substantially to neurological disability in multiple sclerosis (MS). Thus neuroprotective therapies that preserve axons, so that they maintain their integrity and continue to function, might be expected to result in improved neurological outcome. Sodium channels are known to provide a route for sodium influx that can drive calcium influx, via reverse operation of the Na+/Ca2+ exchanger, after injury to axons within the CNS, and sodium channel blockers have been shown to protect CNS axons from degeneration after experimental anoxic, traumatic, and nitric oxide (NO)-induced injury. In this study, we asked whether phenytoin, which is known to block sodium channels, can protect spinal cord axons from degeneration in mice with experimental allergic encephalomyelitis (EAE), which display substantial axonal degeneration and clinical paralysis. We demonstrate that the loss of dorsal corticospinal tract (63%) and dorsal column (cuneate fasciculus; 43%) axons in EAE is significantly ameliorated (corticospinal tract: 28%; cuneate fasciculus: 17%) by treatment with phenytoin. Spinal cord compound action potentials (CAP) were significantly attenuated in untreated EAE, whereas spinal cords from phenytoin-treated EAE had robust CAPs, similar to those from phenytoin-treated control mice. Clinical scores in phenytoin-treated EAE at 28 days were significantly improved (1.5, i.e., minor righting reflex abnormalities) compared with untreated EAE (3.8, i.e., near-complete hindlimb paralysis). Our results demonstrate that phenytoin has a protective effect in vivo on spinal cord axons, preventing their degeneration, maintaining their ability to conduct action potentials, and improving clinical status in a model of neuroinflammation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3077
pubmed:author
pubmed:issnType
Print
pubmed:volume
90
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3566-71
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Phenytoin protects spinal cord axons and preserves axonal conduction and neurological function in a model of neuroinflammation in vivo.
pubmed:affiliation
Department of Neurology and Paralyzed Veterans Association/Eastern Paralyzed Veterans Association of America Neuroscience Research Center, Yale University School of Medicine, New Haven, CT 06510, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't