Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-4-16
pubmed:abstractText
Activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2) are implicated in the pathophysiology of spinal cord injury (SCI). However, the specific functions of individual ERK isoforms in neurodegeneration are largely unknown. We investigated the hypothesis that ERK2 activation may contribute to pathological and functional deficits following SCI and that ERK2 knockdown using RNA interference may provide a novel therapeutic strategy for SCI. Lentiviral ERK2 shRNA and siRNA were utilized to knockdown ERK2 expression in the spinal cord following SCI. Pre-injury intrathecal administration of ERK2 siRNA significantly reduced excitotoxic injury-induced activation of ERK2 (p < 0.001) and caspase 3 (p < 0.01) in spinal cord. Intraspinal administration of lentiviral ERK2 shRNA significantly reduced ERK2 expression in the spinal cord (p < 0.05), but did not alter ERK1 expression. Administration of the lentiviral ERK2 shRNA vector 1 week prior to severe spinal cord contusion injury resulted in a significant improvement in locomotor function (p < 0.05), total tissue sparing (p < 0.05), white matter sparing (p < 0.05), and gray matter sparing (p < 0.05) 6 weeks following severe contusive SCI. Our results suggest that ERK2 signaling is a novel target associated with the deleterious consequences of spinal injury.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1471-4159
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
113
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
131-42
pubmed:dateRevised
2010-7-6
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Involvement of ERK2 in traumatic spinal cord injury.
pubmed:affiliation
Spinal Cord and Brain Injury Research Center and Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, Kentucky 40536-0509, USA. cyu4@uky.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't