GDNF modifies reactive astrogliosis allowing robust axonal regeneration through Schwann cell-seeded guidance channels after spinal cord injury

Ling Xiao Deng, Jianguo Hu, Naikui Liu, Xiaofei Wang, George M. Smith, Xuejun Wen, Xiao-Ming Xu

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Reactive astrogliosis impedes axonal regeneration after injuries to the mammalian central nervous system (CNS). Here we report that glial cell line-derived neurotrophic factor (GDNF), combined with transplanted Schwann cells (SCs), effectively reversed the inhibitory properties of astrocytes at graft-host interfaces allowing robust axonal regeneration, concomitant with vigorous migration of host astrocytes into SC-seeded semi-permeable guidance channels implanted into a right-sided spinal cord hemisection at the 10th thoracic (T10) level. Within the graft, migrated host astrocytes were in close association with regenerated axons. Astrocyte processes extended parallel to the axons, implying that the migrated astrocytes were not inhibitory and might have promoted directional growth of regenerated axons. In vitro, GDNF induced migration of SCs and astrocytes toward each other in an astrocyte-SC confrontation assay. GDNF also enhanced migration of astrocytes on a SC monolayer in an inverted coverslip migration assay, suggesting that this effect is mediated by direct cell-cell contact between the two cell types. Morphologically, GDNF administration reduced astrocyte hypertrophy and induced elongated process extension of these cells, similar to what was observed in vivo. Notably, GDNF treatment significantly reduced production of glial fibrillary acidic protein (GFAP) and chondroitin sulfate proteoglycans (CSPGs), two hallmarks of astrogliosis, in both the in vivo and in vitro models. Thus, our study demonstrates a novel role of GDNF in modifying spinal cord injury (SCI)-induced astrogliosis resulting in robust axonal regeneration in adult rats.

Original languageEnglish
Pages (from-to)238-250
Number of pages13
JournalExperimental Neurology
Volume229
Issue number2
DOIs
StatePublished - Jun 2011

Fingerprint

Glial Cell Line-Derived Neurotrophic Factor
Schwann Cells
Spinal Cord Injuries
Astrocytes
Regeneration
Axons
Chondroitin Sulfate Proteoglycans
Transplants
Glial Fibrillary Acidic Protein
Hypertrophy
Spinal Cord
Thorax
Central Nervous System

Keywords

  • Axonal regeneration
  • GDNF
  • Reactive astrocytes
  • Schwann cells
  • Spinal cord injury
  • Transplantation

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

GDNF modifies reactive astrogliosis allowing robust axonal regeneration through Schwann cell-seeded guidance channels after spinal cord injury. / Deng, Ling Xiao; Hu, Jianguo; Liu, Naikui; Wang, Xiaofei; Smith, George M.; Wen, Xuejun; Xu, Xiao-Ming.

In: Experimental Neurology, Vol. 229, No. 2, 06.2011, p. 238-250.

Research output: Contribution to journalArticle

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