PT  - JOURNAL ARTICLE
AU  - Jin Qiu
AU  - William B. J. Cafferty
AU  - Stephen B. McMahon
AU  - Stephen W. N. Thompson
TI  - Conditioning Injury-Induced Spinal Axon Regeneration Requires Signal Transducer and Activator of Transcription 3 Activation
AID  - 10.1523/JNEUROSCI.3269-04.2005
DP  - 2005 Feb 16
TA  - The Journal of Neuroscience
PG  - 1645--1653
VI  - 25
IP  - 7
4099  - http://www.jneurosci.org/content/25/7/1645.short
4100  - http://www.jneurosci.org/content/25/7/1645.full
SO  - J. Neurosci.2005 Feb 16; 25
AB  - 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.