Neurotrophins BDNF and NT-3 promote axonal re-entry into the distal host spinal cord through Schwann cell-seeded mini-channels

Norman I. Bamber, Huaying Li, Xiaobin Lu, Martin Oudega, Patrick Aebischer, Xiao-Ming Xu

Research output: Contribution to journalArticle

177 Citations (Scopus)

Abstract

To promote axonal regeneration in the injured adult spinal cord, a two-phase repair strategy was employed to (i) bridge a spinal cord hemilesion cavity with a grafted Schwann cell (SC)-seeded mini-channel, and (ii) promote axonal re-entry into the distal cord by infusing two neurotrophins, BDNF and/or NT-3, directly into the distal cord parenchyma. Here we report that infusion of two neurotrophins, delivered alone or in combination, effectively promotes axonal outgrowth from SC-seeded mini-channels into the distal host spinal cord. When an anterogradely transported marker, PHA-L or BDA, was injected into the spinal cord 3 mm rostral to the graft, a large number of axons was observed to regenerate from the SC graft into the distal cord in neurotrophin-treated groups. A subpopulation of these axons was found to grow up to 6 mm within the distal spinal cord. These axons, which were confined mainly within the grey matter, arborized and formed structures which resemble terminal boutons. In channels containing no SCs, the infusion of neurotrophins did not promote axonal ingrowth from the proximal cord stump. In cases which received SC grafts but no neurotrophin infusion, axonal re-entry into the distal cord was limited. Thus, the present study demonstrates that regenerating axons not only cross a lesion site when a permissive cellular bridge is provided but also penetrate into the distal host spinal cord and elongate for a distance of several cord segments after the infusion of two neurotrophins. The latter event is prerequisite for establishment of appropriate connections between regenerating axons and target neurons and thus, functional recovery.

Original languageEnglish (US)
Pages (from-to)257-268
Number of pages12
JournalEuropean Journal of Neuroscience
Volume13
Issue number2
DOIs
StatePublished - 2001
Externally publishedYes

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Schwann Cells
Brain-Derived Neurotrophic Factor
Nerve Growth Factors
Spinal Cord
Axons
Transplants
Regeneration
Neurons

Keywords

  • Rat
  • Regeneration
  • Spinal cord injury
  • Transplantation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Neurotrophins BDNF and NT-3 promote axonal re-entry into the distal host spinal cord through Schwann cell-seeded mini-channels. / Bamber, Norman I.; Li, Huaying; Lu, Xiaobin; Oudega, Martin; Aebischer, Patrick; Xu, Xiao-Ming.

In: European Journal of Neuroscience, Vol. 13, No. 2, 2001, p. 257-268.

Research output: Contribution to journalArticle

Bamber, Norman I. ; Li, Huaying ; Lu, Xiaobin ; Oudega, Martin ; Aebischer, Patrick ; Xu, Xiao-Ming. / Neurotrophins BDNF and NT-3 promote axonal re-entry into the distal host spinal cord through Schwann cell-seeded mini-channels. In: European Journal of Neuroscience. 2001 ; Vol. 13, No. 2. pp. 257-268.
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