Glial cell line-derived neurotrophic factor (GDNF) gene delivery protects cortical neurons from dying following a traumatic brain injury

Jennie E. Minnich, Sarah L. Mann, Megan Stock, Kathryn A. Stolzenbach, Bridget M. Mortell, Katherine E. Soderstrom, Martha C. Bohn, Dorothy A. Kozlowski

Research output: Contribution to journalArticle

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)293-309
Number of pages17
JournalRestorative Neurology and Neuroscience
Volume28
Issue number3
DOIs
StatePublished - Jul 23 2010

Keywords

  • Traumatic brain injury
  • behavioral assessments
  • controlled cortical impact
  • forelimb sensorimotor cortex
  • growth factors

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Clinical Neurology

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