Linked Life Data

8834390

Source:http://linkedlifedata.com/resource/pubmed/id/8834390

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1996-11-27
pubmed:abstractText
Protection of CNS white matter tracts in brain and spinal cord is essential for maximizing clinical recovery from disorders such as stroke or spinal cord injury. Central myelinated axons are damaged by anoxia/ischemia in a Ca(2+)-dependent manner. Leakage of Na+ into the axoplasm through Na+ channels causes Ca2+ overload mainly by reverse Na(+)-Ca2+ exchange. Na+ channel blockers have thus been shown to be protective in an in vitro anoxic rat optic nerve model. Mexiletine (10 microM-1 mM), an antiarrhythmic and use-dependent Na+ channel blocker, was also significantly protective, as measured by recovery of the compound action potential after a 60 min anoxic exposure in vitro. More importantly, mexiletine (80 mg/kg, i.p.) also significantly protected optic nerves from injury in a model of in situ ischemia. This in situ model is more clinically relevant as it addresses drug pharmacokinetics, toxicity and CNS penetration. Optic nerve recovery cycles (defined as shifts in latency of compound action potentials with paired stimulation) were used to measure the concentration of mexiletine in optic nerves after systemic administration, estimated at approximately 42 microM 1 h after a single dose of 80 mg/kg, i.p. These results indicate that mexiletine is able to penetrate into the CNS at concentrations sufficient to confer significant protection. Na+ channel blockers such as mexiletine may prove to be effective clinical therapeutic agents for protecting CNS white matter tracts against anoxic/ischemic injury.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
27-36
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Correlation between electrophysiological effects of mexiletine and ischemic protection in central nervous system white matter.
pubmed:affiliation
Division of Neuroscience, University of Ottawa, Canada.
pubmed:publicationType
Journal Article, In Vitro