Adeno-associated viral vector-mediated neurotrophin gene transfer in the injured adult rat spinal cord improves hind-limb function

B Blits, M. Oudega, G J Boer, M Bartlett Bunge, J Verhaagen

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

To foster axonal growth from a Schwann cell bridge into the caudal spinal cord, spinal cells caudal to the implant were transduced with adeno-associated viral (AAV) vectors encoding for brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (AAV-NT-3). Control rats received AAV vectors encoding for green fluorescent protein or saline. AAV-BDNF- and AAV-NT-3-transduced 293 human kidney cells produced and secreted BDNF or NT-3, respectively, in vitro. The secreted neurotrophins were biologically active; they both promoted outgrowth of sensory neurites in vitro. In vivo, transgene expression was observed predominantly in neurons for at least 16 weeks after injection. Compared with controls, a modest though significant improvement in hind-limb function was found in rats that received AAV-BDNF and AAV-NT-3. Retrograde tracing demonstrated that twice as many neurons with processes extending toward the Schwann cell graft were present in the second lumbar cord segment of AAV-BDNF- and AAV-NT-3-injected animals compared with controls. We found no evidence, however, for growth of regenerated axons from the Schwann cell implant into the caudal cord. Our results suggest that AAV vector-mediated overexpression of BDNF and NT-3 in the cord caudal to a Schwann cell bridge modified the local lumbar axonal circuitry, which was beneficial for locomotor function.

Original languageEnglish
Pages (from-to)271-81
Number of pages11
JournalNeuroscience
Volume118
Issue number1
Publication statusPublished - 2003

Keywords

  • Adenoviridae
  • Animals
  • Brain Tissue Transplantation
  • Brain-Derived Neurotrophic Factor
  • Female
  • Fluorescent Dyes
  • Gene Transfer Techniques
  • Genetic Vectors
  • Graft Survival
  • Growth Cones
  • Hindlimb
  • Nerve Growth Factors
  • Nerve Regeneration
  • Neural Pathways
  • Neurotrophin 3
  • Rats
  • Rats, Inbred F344
  • Recombinant Fusion Proteins
  • Recovery of Function
  • Schwann Cells
  • Spinal Cord
  • Spinal Cord Injuries
  • Treatment Outcome
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

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