A neuroprotective role of glial cell line-derived neurotrophic factor following moderate spinal cord contusion injury

Christopher Iannotti, Y. Ping Zhang, Christopher B. Shields, Yingchun Han, Darlene A. Burke, Xiao-Ming Xu

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

The present study investigated neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF), a distant member of the transforming growth factor-β (TGF-β) superfamily, following moderate contusive spinal cord injury (SCI) in adult rats. A T11 spinal cord contusion injury was made using an Infinite Horizon impactor (IH; impact force = 150 kDyn) and recombinant human GDNF at two concentrations (rhGDNF; 1 or 5 μg/μl), or saline vehicle was delivered intrathecally for 28 days using an Alzet miniosmotic pump. We demonstrated that, at 7 weeks postinjury, GDNF infusion significantly reduced the total lesion volume by 34-42% (assessed stereologically) and increased the percentage of white matter sparing by 10-13% (measured at the injury epicenter), as compared to the vehicle infusion. Retrograde tracing revealed that GDNF infusion resulted in a significant increase in the number of FluoroGold (FG)-labeled neurons in propriospinal regions as well as in two supraspinal regions, that is, the medullary and pontine reticular formation, and the lateral vestibular nucleus. Immunofluorescent staining confirmed that the spared white matter contained neurofilament-positive axons. However, transcranial magnetic motor-evoked potential (tcMMEP) assessment revealed no significant difference in onset latency and amplitude between the GDNF- and vehicle-infused groups. These results suggest that GDNF has a strong neuroprotective effect on white matter sparing and the sparing of a subset of proprio- and supraspinal axons following injury. However, a return of tcMMEPs requires the sparing and/or myelination of axons in a defined region of the white matter which was either not spared or remyelinated at this level of injury severity.

Original languageEnglish (US)
Pages (from-to)317-332
Number of pages16
JournalExperimental Neurology
Volume189
Issue number2
DOIs
StatePublished - Oct 2004
Externally publishedYes

Fingerprint

Glial Cell Line-Derived Neurotrophic Factor
Spinal Cord Injuries
Axons
Neuroprotective Agents
Wounds and Injuries
Lateral Vestibular Nucleus
Motor Evoked Potentials
Intermediate Filaments
Transforming Growth Factors
Staining and Labeling
Neurons
White Matter

Keywords

  • Contusion
  • GDNF
  • Neuroprotection
  • Neurotrophic factors
  • Spinal cord injury
  • tcMMEP

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

A neuroprotective role of glial cell line-derived neurotrophic factor following moderate spinal cord contusion injury. / Iannotti, Christopher; Ping Zhang, Y.; Shields, Christopher B.; Han, Yingchun; Burke, Darlene A.; Xu, Xiao-Ming.

In: Experimental Neurology, Vol. 189, No. 2, 10.2004, p. 317-332.

Research output: Contribution to journalArticle

Iannotti, Christopher ; Ping Zhang, Y. ; Shields, Christopher B. ; Han, Yingchun ; Burke, Darlene A. ; Xu, Xiao-Ming. / A neuroprotective role of glial cell line-derived neurotrophic factor following moderate spinal cord contusion injury. In: Experimental Neurology. 2004 ; Vol. 189, No. 2. pp. 317-332.
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