A combination of BDNF and NT-3 promotes supraspinal axonal regeneration into schwann cell grafts in adult rat thoracic spinal cord

Xiao Ming Xu, Véronique Guénard, Naomi Kleitman, Patrick Aebischer, Mary Bartlett Bunge

Research output: Contribution to journalArticle

399 Scopus citations

Abstract

We previously demonstrated that Schwann cells (SCs) in semipermeable guidance channels promote axonal regeneration in adult rat spinal cord transected at the mid-thoracic level. Propriospinal but not supraspinal axons grew into these channels. Here, we tested the ability of exogenous brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) to promote axonal regeneration in this novel model. The two neurotrophins were delivered simultaneously into the channel by an Alzet minipump at a rate of 12 μg/day for each neurotrophin for 14 of 30 days tested; phosphate-buffered saline, the vehicle solution, was used as a control. Significantly more myelinated nerve fibers were present in SC/neurotrophin grafts than in SC/vehicle grafts (1523 ± 292 vs 882 ± 287). In the graft, at least 5 mm from the rostral cord-graft interface, some nerve fibers were immunoreactive for serotonin, a neurotransmitter specific to raphe-derived axons in rat spinal cord. Fast blue retrograde tracing from SC/neurotrophin grafts revealed labeled neurons in 10 nuclei of the brain stem, 67% of these being in the lateral and spinal vestibular nuclei. The mean number of labeled brain stem neurons in the SC/neurotrophin group (92; n = 3) contrasted with the mean in the SC/vehicle group (6; n = 4). Our results clearly demonstrate that BDNF and NT-3 infusion enhanced propriospinal axonal regeneration and, more significantly, promoted axonal regeneration of specific distant populations of brain stem neurons into grafts at the mid-thoracic level in adult rat spinal cord.

Original languageEnglish (US)
Pages (from-to)261-272
Number of pages12
JournalExperimental Neurology
Volume134
Issue number2
DOIs
StatePublished - Aug 1995
Externally publishedYes

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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