Glial cell line-derived neurotrophic factor (GDNF) gene delivery protects cortical neurons from dying following a traumatic brain injury.
OBJECTIVE
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.
Minnich
Jennie E
JE
Department of Biological Sciences, DePaul University, Chicago, IL 60614, USA.
Mann
Sarah L
SL
Stock
Megan
M
Stolzenbach
Kathryn A
KA
Mortell
Bridget M
BM
Soderstrom
Katherine E
KE
Bohn
Martha C
MC
Kozlowski
Dorothy A
DA
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001930:Brain Injuries / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000235:genetics*; D007794:Lameness, Animal / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D008297:Male; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology / Q000628:therapy; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020127:Recovery of Function / Q000235:genetics
C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents