Affiliations: Traumatic Brain Injury Laboratory, Department of
Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA | Veterans Administration Medical Center, Philadelphia,
PA, USA | Neurosurgical Intensive Care Unit, Department of
Anesthesia and Critical Care Medicine, University of Milan, Ospedale Maggiore
Policlinico, Mangiagallie Regina Elena Fondazione, IRCCS, Milano, Italy | Department of Neurobiology & Anatomy, Drexel
University College of Medicine, Philadelphia, PA, USA
Note: [] Corresponding author: Ramesh Raghupathi, Ph.D., Department of
Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen
Lane, Philadelphia, PA 19129, USA. Tel.: +1 215 991 8405; Fax: +1 215 843 9082;
E-mail: [email protected]
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.
Keywords: Adeno-associated virus, cell death, cognition, in vivo gene therapy, neurotrophins
