TrkB gene transfer does not alter hippocampal neuronal loss and cognitive deficits following traumatic brain injury in mice

Valeria Conte, Ramesh Raghupathi, Deborah J. Watson, Scott Fujimoto, Nicolas C. Royo, Niklas Marklund, Nino Stocchetti, Tracy K. McIntosh

Research output: Contribution to journalArticle

Abstract

Purpose: The ability of brain-derived neurotrophic factor (BDNF) to attenuate secondary damage and influence behavioral outcome after experimental traumatic brain injury (TBI) remains controversial. Because TBI can result in decreased expression of the trkB receptor, thereby preventing BDNF from exerting potential neuroprotective effects, the contribution of both BDNF and its receptor trkB to hippocampal neuronal loss and cognitive dysfunction were evaluated. Methods: Full-length trkB was overexpressed in the left hippocampus of adult C57Bl/6 mice using recombinant adeno-associated virus serotype 2/5 (rAAV 2/5). EGFP (enhanced green fluorescent protein) expression was present at two weeks after AAV-EGFP injection and remained sustained up to four weeks after the injection. At 2 weeks following gene transduction, mice were subjected to parasagittal controlled cortical impact (CCI) brain injury, followed by either BDNF or PBS infusion into the hippocampus. Results: No differences were observed in learning ability at two weeks post-injury or in motor function from 48 hours to two weeks among treatment groups. The number of surviving pyramidal neurons in the CA2-CA3 region of the hippocampus was also not different among treatment groups. Conclusions: These data suggest that neither overexpression of trkB, BNDF infusion or their combination affects neuronal survival or behavioral outcome following experimental TBI in mice.

Original languageEnglish
Pages (from-to)45-56
Number of pages12
JournalRestorative Neurology and Neuroscience
Volume26
Issue number1
Publication statusPublished - 2008

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Keywords

  • Adeno-associated virus
  • Cell death
  • Cognition
  • In vivo gene therapy
  • Neurotrophins

ASJC Scopus subject areas

  • Neuroscience(all)
  • Neuropsychology and Physiological Psychology

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