Combined Intrinsic and Extrinsic Neuronal Mechanisms Facilitate Bridging Axonal Regeneration One Year after Spinal Cord Injury

Ken Kadoya, Shingo Tsukada, Paul Lu, Giovanni Coppola, Dan Geschwind, Marie T. Filbin, Armin Blesch, Mark H. Tuszynski

Research output: Contribution to journalArticlepeer-review

178 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)165-172
Number of pages8
JournalNeuron
Volume64
Issue number2
DOIs
StatePublished - 29 Oct 2009
Externally publishedYes

Keywords

  • CELLBIO
  • HUMDISEASE
  • MOLNEURO

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