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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2005-2-17
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pubmed:abstractText |
Sensory axons in the adult spinal cord do not regenerate after injury. This is essentially because of inhibitory components in the damaged CNS, such as myelin-associated inhibitors and the glial scar. However, if the sciatic nerve is axotomized before injury of the dorsal column, injured axons can regenerate a short distance in the spinal cord. Here, we show that sciatic nerve transection results in time-dependent phosphorylation and activation of the transcription factor, signal transducer and activator of transcription 3 (STAT3), in dorsal root ganglion (DRG) neurons. This effect is specific to peripheral injuries and does not occur when the dorsal column is crushed. Sustained perineural infusion of the Janus kinase 2 (JAK2) inhibitor AG490 to the proximal nerve stump can block STAT3 phosphorylation after sciatic nerve transection and results in reduced growth-associated protein 43 upregulation and compromised neurite outgrowth in vitro. Importantly, in vivo perineural infusion of AG490 also significantly attenuates dorsal column axonal regeneration in the adult spinal cord after a preconditioning sciatic nerve transection. We conclude that STAT3 activation is necessary for increased growth ability of DRG neurons and improved axonal regeneration in the spinal cord after a conditioning injury.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Cholera Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokine Receptor gp130,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GAP-43 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Il6st protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Jak2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/STAT3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Stat3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-cyano-(3,4-dihydroxy)-N-benzyl...
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1529-2401
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
16
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1645-53
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15716400-Animals,
pubmed-meshheading:15716400-Antigens, CD,
pubmed-meshheading:15716400-Axons,
pubmed-meshheading:15716400-Axotomy,
pubmed-meshheading:15716400-Cells, Cultured,
pubmed-meshheading:15716400-Cholera Toxin,
pubmed-meshheading:15716400-Cytokine Receptor gp130,
pubmed-meshheading:15716400-DNA-Binding Proteins,
pubmed-meshheading:15716400-GAP-43 Protein,
pubmed-meshheading:15716400-Ganglia, Spinal,
pubmed-meshheading:15716400-Infusion Pumps, Implantable,
pubmed-meshheading:15716400-Janus Kinase 2,
pubmed-meshheading:15716400-Male,
pubmed-meshheading:15716400-Membrane Glycoproteins,
pubmed-meshheading:15716400-Nerve Crush,
pubmed-meshheading:15716400-Nerve Regeneration,
pubmed-meshheading:15716400-Neurites,
pubmed-meshheading:15716400-Phosphorylation,
pubmed-meshheading:15716400-Protein Processing, Post-Translational,
pubmed-meshheading:15716400-Protein-Tyrosine Kinases,
pubmed-meshheading:15716400-Proto-Oncogene Proteins,
pubmed-meshheading:15716400-Rats,
pubmed-meshheading:15716400-Rats, Wistar,
pubmed-meshheading:15716400-STAT3 Transcription Factor,
pubmed-meshheading:15716400-Sciatic Nerve,
pubmed-meshheading:15716400-Signal Transduction,
pubmed-meshheading:15716400-Spinal Cord Injuries,
pubmed-meshheading:15716400-Trans-Activators,
pubmed-meshheading:15716400-Tyrphostins
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pubmed:year |
2005
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pubmed:articleTitle |
Conditioning injury-induced spinal axon regeneration requires signal transducer and activator of transcription 3 activation.
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pubmed:affiliation |
Wolfson Centre for Age-Related Diseases, Guy's, King's, and St. Thomas's School of Biomedical Science, King's College London, London SE1 1UL, United Kingdom.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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