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

Conte, Valeria ; Raghupathi, Ramesh ; Watson, Deborah J ; Fujimoto, Scott ; Royo, Nicolas C ; Marklund, Niklas LU ; Stocchetti, Nino and McIntosh, Tracy K (2008) In Restorative Neurology and Neuroscience 26(1). p.45-56
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... (More)

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.

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; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Analysis of Variance, Animals, Brain Injuries, Cell Count, Cognition Disorders, Dependovirus, Disease Models, Animal, Green Fluorescent Proteins, Hippocampus, Male, Maze Learning, Mice, Mice, Inbred C57BL, Motor Activity, Neurons, Reaction Time, Receptor, trkB, Time Factors, Transduction, Genetic
in
Restorative Neurology and Neuroscience
volume
26
issue
1
pages
45 - 56
publisher
IOS Press
external identifiers
  • scopus:43249085575
  • pmid:18431005
ISSN
0922-6028
language
English
LU publication?
no
id
9d144c9b-5db8-46e4-b5d1-b326d03cca21
date added to LUP
2018-03-03 14:47:27
date last changed
2020-05-26 04:38:53
@article{9d144c9b-5db8-46e4-b5d1-b326d03cca21,
  abstract     = {<p>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.</p><p>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.</p><p>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.</p><p>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.</p>},
  author       = {Conte, Valeria and Raghupathi, Ramesh and Watson, Deborah J and Fujimoto, Scott and Royo, Nicolas C and Marklund, Niklas and Stocchetti, Nino and McIntosh, Tracy K},
  issn         = {0922-6028},
  language     = {eng},
  number       = {1},
  pages        = {45--56},
  publisher    = {IOS Press},
  series       = {Restorative Neurology and Neuroscience},
  title        = {TrkB gene transfer does not alter hippocampal neuronal loss and cognitive deficits following traumatic brain injury in mice},
  volume       = {26},
  year         = {2008},
}