Journal
NEURON
Volume 64, Issue 2, Pages 165-172Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2009.09.016
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Funding
- NIH [R01 NS09881, NS054883]
- Veterans Administration, International Spinal Research Trust
- Bernard and Anne Spitzer Charitable Trust
- Dr. Miriam and Sheldon G Adelson Medical Research Foundation
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Despite advances in promoting axonal regeneration after acute spinal cord injury (SCI), elicitation of bridging axon regeneration after chronic SCI remains a formidable challenge. We report that combinatorial therapies administered 6 weeks, and as long as 15 months, after SCI promote axonal regeneration into and beyond a midcervical lesion site. Provision of peripheral nerve conditioning lesions, grafts of marrow stromal cells, and establishment of NT-3 gradients supports bridging regeneration. Controls receiving partial components of the full combination fail to exhibit bridging. Notably, intraneuronal molecular mechanisms recruited by delayed therapies mirror those of acute injury, including activation of transcriptional activators and regeneration-associated genes. Collectively, these findings provide evidence that regeneration is achievable at unprecedented postinjury time points.
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