Glial cell line-derived neurotrophic factor-enriched bridging transplants promote propriospinal axonal regeneration and enhance myelination after spinal cord injury

Christopher Iannotti, Huayin Li, Ping Yan, Xiaobin Lu, Louisa Wirthlin, Xiao-Ming Xu

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Glial cell line-derived neurotrophic factor (GDNF), a distant member of the transforming growth factor-β (TGF-β) family, is widely expressed in the developing and adult central nervous system (CNS). At present, limited information is available regarding the effects of GDNF in the repair of spinal cord injury (SCI). In the present study, mini-guidance channels containing either: (1) Matrigel (MG, a basement membrane component), (2) Schwann cells (SCs, 120 × 106/ml) in MG (SC-MG), (3) recombinant human GDNF (rhGDNF, 3 μg/μl) in MG (GDNF-MG), and (4) a combination of all three components (GDNF-SC-MG) were grafted into a T9 hemisection-gap lesion in adult rats to examine the effects of GDNF on axonal regeneration and myelination following SCI. Thirty days post-transplantation, limited axonal growth was observed within guidance channels containing MG-alone (MG). When SCs were added to the channels (SC-MG group), consistent axonal ingrowth containing both myelinated and unmyelinated axons was observed, confirming our previous findings. The addition of GDNF-alone without SCs (GDNF-MG) resulted in substantial ingrowth of unmyelinated axons, suggesting that GDNF has a direct neurite-growth promoting effect on these axons. Implantation of channels containing both GDNF and SCs (GDNF-SC-MG) produced a significant and synergistic increase in axonal regeneration and myelination. In addition, GDNF reduced the extent of reactive gliosis, infiltration of activated macrophages/microglia, and cystic cavitation at the graft-host interfaces. Retrograde tracing revealed that grafts of SC-seeded channels containing GDNF promoted a significant increase in the number of propriospinal neurons which had regenerated their axons into the grafts, as compared to SC-MG-seeded channels. These results indicate that GDNF may play a novel therapeutic role in promoting propriospinal axonal regeneration, enhancing myelin formation, and improving graft-host interfaces after SCI.

Original languageEnglish (US)
Pages (from-to)379-393
Number of pages15
JournalExperimental Neurology
Volume183
Issue number2
DOIs
StatePublished - Oct 1 2003
Externally publishedYes

Fingerprint

Glial Cell Line-Derived Neurotrophic Factor
Spinal Cord Injuries
Regeneration
Transplants
Axons
Gliosis
Schwann Cells
Microglia
Transforming Growth Factors
Neurites
Growth
Myelin Sheath
Basement Membrane

Keywords

  • Axonal regeneration
  • GDNF
  • Guidance channels
  • Hemisection
  • Myelination
  • Neurotrophic factors
  • Schwann cells
  • Spinal cord injury
  • Transplantation

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Glial cell line-derived neurotrophic factor-enriched bridging transplants promote propriospinal axonal regeneration and enhance myelination after spinal cord injury. / Iannotti, Christopher; Li, Huayin; Yan, Ping; Lu, Xiaobin; Wirthlin, Louisa; Xu, Xiao-Ming.

In: Experimental Neurology, Vol. 183, No. 2, 01.10.2003, p. 379-393.

Research output: Contribution to journalArticle

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AU - Wirthlin, Louisa

AU - Xu, Xiao-Ming

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AB - Glial cell line-derived neurotrophic factor (GDNF), a distant member of the transforming growth factor-β (TGF-β) family, is widely expressed in the developing and adult central nervous system (CNS). At present, limited information is available regarding the effects of GDNF in the repair of spinal cord injury (SCI). In the present study, mini-guidance channels containing either: (1) Matrigel (MG, a basement membrane component), (2) Schwann cells (SCs, 120 × 106/ml) in MG (SC-MG), (3) recombinant human GDNF (rhGDNF, 3 μg/μl) in MG (GDNF-MG), and (4) a combination of all three components (GDNF-SC-MG) were grafted into a T9 hemisection-gap lesion in adult rats to examine the effects of GDNF on axonal regeneration and myelination following SCI. Thirty days post-transplantation, limited axonal growth was observed within guidance channels containing MG-alone (MG). When SCs were added to the channels (SC-MG group), consistent axonal ingrowth containing both myelinated and unmyelinated axons was observed, confirming our previous findings. The addition of GDNF-alone without SCs (GDNF-MG) resulted in substantial ingrowth of unmyelinated axons, suggesting that GDNF has a direct neurite-growth promoting effect on these axons. Implantation of channels containing both GDNF and SCs (GDNF-SC-MG) produced a significant and synergistic increase in axonal regeneration and myelination. In addition, GDNF reduced the extent of reactive gliosis, infiltration of activated macrophages/microglia, and cystic cavitation at the graft-host interfaces. Retrograde tracing revealed that grafts of SC-seeded channels containing GDNF promoted a significant increase in the number of propriospinal neurons which had regenerated their axons into the grafts, as compared to SC-MG-seeded channels. These results indicate that GDNF may play a novel therapeutic role in promoting propriospinal axonal regeneration, enhancing myelin formation, and improving graft-host interfaces after SCI.

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