Affiliations: Department of Biological Sciences, DePaul University,
Chicago, IL, USA | Department of Pediatrics, Children's Memorial Research
Center, Feinberg School of Medicine, Northwestern University, Chicago, IL,
USA
Note: [] Corresponding author: Dorothy Kozlowski Ph.D., Department of
Biological Sciences, DePaul University, 2325 N. Clifton, Chicago, IL 60614,
USA. Tel.: +1 773 325 2191; Fax: +1 773 325 7596; E-mail: [email protected]
Abstract: Purpose: The therapeutic potential of glial cell line-derived
neurotrophic factor (GDNF) gene delivery was examined in a rodent model of
traumatic brain injury (TBI), the controlled cortical impact (CCI). Methods: An adenoviral vector harboring human GDNF (AdGDNF) or green
fluorescent protein (AdGFP) was injected unilaterally into the forelimb
sensorimotor cortex (FL-SMC) of the rat one week prior to a unilateral CCI.
Tests of forelimb function and asymmetry were administered for 2 weeks
post-injury. At 2 weeks post-injury, animals were sacrificed and contusion
size, neuronal survival, neurodegeneration, and virally-mediated GDNF and GFP
protein expression were measured. Results: Rats injected with AdGDNF had
significantly smaller contusions, more surviving neurons, and less
neurodegeneration than AdGFP injected and uninjected injured animals. GDNF gene
delivery also resulted in significantly faster recovery of forelimb
coordination and a smaller initial preference for the uninjured forelimb during
exploration of the walls of a platform. However, overall recovery of
symmetrical forelimb use was not achieved. Conclusions: The discrepancy
between neural protection and behavioral recovery suggests that while GDNF gene
delivery provided a high degree of protection of damaged cortical neurons in
this model of TBI, it may not have fully protected their terminals and synaptic
functioning, resulting in only mild protection against behavioral deficits.
