title: Glial cell line-derived neurotrophic factor (GDNF) gene delivery protects cortical neurons from dying following a traumatic brain injury.
abstract: 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.
authors.affiliation: Department of Biological Sciences, DePaul University, Chicago, IL 60614, USA.
authors.forename: Jennie E
authors.initials: JE
authors.lastname: Minnich
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Mann
authors.forename: Megan
authors.initials: M
authors.lastname: Stock
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Stolzenbach
authors.forename: Bridget M
authors.initials: BM
authors.lastname: Mortell
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Soderstrom
authors.forename: Martha C
authors.initials: MC
authors.lastname: Bohn
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: Kozlowski
mesh_terms: 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
chemical_list: C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents