Neuroprotection of glial cell line-derived neurotrophic factor in damaged spinal cords following contusive injury

Henrich Cheng, Jey Pei Wu, Shun-Fen Tzeng

Research output: Contribution to journalShort survey

94 Citations (Scopus)

Abstract

Glial cell line-derived neurotrophic factor (GDNF) acts as a potent survival factor for many neuronal populations, including spinal motoneurons, indicating the therapeutic promise of GDNF for neurological disorders. Injury to spinal cord (SCI) triggers processes destructive to ascending sensory and descending motor conduction and extends tissue loss, thereby leading to permanent behavioral dysfunction. In this study, we attempted to examine whether GDNF protects neurons from SCI and subsequently lessens locomotor deficit in SCI rats. We utilized the NYU weight-drop device developed at New York University to induce spinal cord contusion at the T9-10 spinal segment. After SCI, GDNF was administrated into the cord 1-2 mm rostral and caudal to the epicenter. Animals receiving GDNF treatment showed significant improvement over phosphate-buffered saline (PBS)-treated controls on the Basso Beattie Bresnahan (BBB) locomotor rating scale (P < 0.01-0.001). GDNF treatment increased the remaining neuronal fibers with calcitonin gene-related peptide, neurofilament, and growth-associated protein 43 immunoreactivity in injured spinal tissues compared with PBS-treated controls. Moreover, treatment with GDNF caused approximately 50% cell survival in the contused spinal cord tissues. Examination of signal transduction triggered by GDNF indicated that GDNF injection transiently induced activation of the mitogen-activated protein (MAP) kinase pathway in the spinal cord. Additionally, an up-regulation of anti-apoptotic Bcl-2 levels in the contusive center of the damaged spinal cord was observed 24 hr post-GDNF injection. Together our results show that GDNF exerts behavioral and anatomic neuroprotection following SCI. Additionally, GDNF-activated MAP kinase and Bcl-2 signaling may contribute to neuronal survival after spinal cord contusion.

Original languageEnglish
Pages (from-to)397-405
Number of pages9
JournalJournal of Neuroscience Research
Volume69
Issue number3
DOIs
Publication statusPublished - 2002 Aug 1

Fingerprint

Glial Cell Line-Derived Neurotrophic Factor
Spinal Cord
Wounds and Injuries
Spinal Cord Injuries
Neuroprotection
Phosphates
GAP-43 Protein
Injections
Intermediate Filaments
Calcitonin Gene-Related Peptide
Contusions
Mitogen-Activated Protein Kinase 1
Motor Neurons
Therapeutics
Mitogen-Activated Protein Kinases
Nervous System Diseases
Signal Transduction
Cell Survival
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

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title = "Neuroprotection of glial cell line-derived neurotrophic factor in damaged spinal cords following contusive injury",
abstract = "Glial cell line-derived neurotrophic factor (GDNF) acts as a potent survival factor for many neuronal populations, including spinal motoneurons, indicating the therapeutic promise of GDNF for neurological disorders. Injury to spinal cord (SCI) triggers processes destructive to ascending sensory and descending motor conduction and extends tissue loss, thereby leading to permanent behavioral dysfunction. In this study, we attempted to examine whether GDNF protects neurons from SCI and subsequently lessens locomotor deficit in SCI rats. We utilized the NYU weight-drop device developed at New York University to induce spinal cord contusion at the T9-10 spinal segment. After SCI, GDNF was administrated into the cord 1-2 mm rostral and caudal to the epicenter. Animals receiving GDNF treatment showed significant improvement over phosphate-buffered saline (PBS)-treated controls on the Basso Beattie Bresnahan (BBB) locomotor rating scale (P < 0.01-0.001). GDNF treatment increased the remaining neuronal fibers with calcitonin gene-related peptide, neurofilament, and growth-associated protein 43 immunoreactivity in injured spinal tissues compared with PBS-treated controls. Moreover, treatment with GDNF caused approximately 50{\%} cell survival in the contused spinal cord tissues. Examination of signal transduction triggered by GDNF indicated that GDNF injection transiently induced activation of the mitogen-activated protein (MAP) kinase pathway in the spinal cord. Additionally, an up-regulation of anti-apoptotic Bcl-2 levels in the contusive center of the damaged spinal cord was observed 24 hr post-GDNF injection. Together our results show that GDNF exerts behavioral and anatomic neuroprotection following SCI. Additionally, GDNF-activated MAP kinase and Bcl-2 signaling may contribute to neuronal survival after spinal cord contusion.",
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Neuroprotection of glial cell line-derived neurotrophic factor in damaged spinal cords following contusive injury. / Cheng, Henrich; Wu, Jey Pei; Tzeng, Shun-Fen.

In: Journal of Neuroscience Research, Vol. 69, No. 3, 01.08.2002, p. 397-405.

Research output: Contribution to journalShort survey

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