Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury

Marc J Ruitenberg, Bas Blits, Paul A Dijkhuizen, Erik T te Beek, Arne Bakker, Joop J van Heerikhuize, Chris W Pool, Wim T J M C Hermens, Gerard J Boer, J. Verhaagen

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

Rubrospinal neurons (RSNs) undergo marked atrophy after cervical axotomy. This progressive atrophy may impair the regenerative capacity of RSNs in response to repair strategies that are targeted to promote rubrospinal tract regeneration. Here, we investigated whether we could achieve long-term rescue of RSNs from lesion-induced atrophy by adeno-associated viral (AAV) vector-mediated gene transfer of brain-derived neurotrophic factor (BDNF). We show for the first time that AAV vectors can be used for the persistent transduction of highly atrophic neurons in the red nucleus (RN) for up to 18 months after injury. Furthermore, BDNF gene transfer into the RN following spinal axotomy resulted in counteraction of atrophy in both the acute and chronic stage after injury. These novel findings demonstrate that a gene therapeutic approach can be used to reverse atrophy of lesioned CNS neurons for an extended period of time.

Original languageEnglish
Pages (from-to)394-406
Number of pages13
JournalNeurobiology of Disease
Volume15
Issue number2
DOIs
Publication statusPublished - Mar 2004

Keywords

  • Acute Disease
  • Animals
  • Atrophy
  • Axotomy
  • Brain-Derived Neurotrophic Factor
  • Chronic Disease
  • Dependovirus
  • Disease Models, Animal
  • Efferent Pathways
  • Gene Transfer Techniques
  • Genetic Vectors
  • Male
  • Nerve Regeneration
  • Neurons
  • Rats
  • Reaction Time
  • Receptor, trkB
  • Red Nucleus
  • Retrograde Degeneration
  • Spinal Cord
  • Spinal Cord Injuries
  • Journal Article
  • Research Support, Non-U.S. Gov't

Fingerprint Dive into the research topics of 'Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury'. Together they form a unique fingerprint.

  • Cite this