Effects of Neurotoxic and Neuroprotective Agents on Peripheral Nerve Regeneration Assayed by Time-Lapse Imaging In Vivo

Y. Albert Pan, Thomas Misgeld, Jeff W. Lichtman, Joshua R. Sanes

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

A direct histological assay of axonal regeneration would have many advantages over currently available behavioral, electrophysiological, and radiometric assays. We show that peripheral sensory axons marked with the yellow fluorescent protein in transgenic mice can be viewed transcutaneously in superficial nerves. Degenerating and regenerating axons can be followed in live animals with a dissecting microscope and then, after fixation, studied at high resolution by confocal microscopy. Using this approach, we document differences in regenerative ability after nerve transection, crush injury, and crush injury after a previous "conditioning" lesion. We also show that the chemotherapeutic drug vincristine rapidly but transiently blocks regeneration and that the immunosuppressive drug FK506 modestly enhances regeneration. Moreover, FK506 nearly restores normal regenerative ability in animals treated with submaximal doses of vincristine. Because neuropathy is the major dose-limiting side effect of vincristine, we propose that its efficacy could be enhanced by coadministration of FK506 analogs that are neuroactive but not immunosuppressive.

Original languageEnglish (US)
Pages (from-to)11479-11488
Number of pages10
JournalJournal of Neuroscience
Volume23
Issue number36
DOIs
StatePublished - Dec 10 2003

Keywords

  • Conditioning lesion
  • FK506
  • Regeneration
  • Transgenic mice
  • Vincristine
  • Wallerian degeneration

ASJC Scopus subject areas

  • Neuroscience(all)

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