STAT3 promotes corticospinal remodelling and functional recovery after spinal cord injury

If and how neurons remodel their connections after CNS injury critically influences recovery of function. Here, we investigate the role of the growth‐initiating transcription factor STAT3 during remodelling of the injured corticospinal tract (CST). Endogenous STAT3 expression in lesioned cortical pr...

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Bibliographic Details
Published in:EMBO reports 2013-10, Vol.14 (10), p.931-937
Main Authors: Lang, Claudia, Bradley, Peter M, Jacobi, Anne, Kerschensteiner, Martin, Bareyre, Florence M
Format: Article
Language:English
Subjects:
Animals
axonal remodelling
Central nervous system
corticospinal tract
EMBO27
Fibers
Gene Deletion
Gene expression
Mice
Mice, Inbred C57BL
Molecular biology
Nerve Regeneration
neuronal plasticity
Neurons
Neurons - metabolism
Proteins
Pyramidal Tracts - metabolism
Pyramidal Tracts - physiology
Scientific Report
Scientific Reports
Spinal cord injuries
Spinal Cord Injuries - metabolism
Spinal Cord Injuries - pathology
spinal cord injury
STAT3
STAT3 Transcription Factor - genetics
STAT3 Transcription Factor - metabolism
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Summary:If and how neurons remodel their connections after CNS injury critically influences recovery of function. Here, we investigate the role of the growth‐initiating transcription factor STAT3 during remodelling of the injured corticospinal tract (CST). Endogenous STAT3 expression in lesioned cortical projection neurons is transient but can be sustained by viral gene transfer. Sustained activation of STAT3 enhances remodelling of lesioned CST fibres and induces de novo formation of collaterals from unlesioned CST fibres. In a unilateral pyramidotomy paradigm, this recruitment of unlesioned fibres leads to the formation of midline crossing circuits that establish ipsilateral forelimb activation and functional recovery. Sustained STAT3 activation promotes the remodeling of damaged fibers in the injured spinal cord. It also recruits undamaged fibers from the contralateral site that cross the midline and restore ipsilateral forelimb function.
ISSN:1469-221X
1469-3178
DOI:10.1038/embor.2013.117