The extracellular matrix glycoprotein tenascin-c is beneficial for spinal cord regeneration

Jian Chen, Hyun Joon Lee, Igor Jakovcevski, Ronak Shah, Neha Bhagat, Gabriele Loers, Hsing Yin Liu, Sally Meiners, Grit Taschenberger, Sebastian Kügler, Andrey Irintchev, Melitta Schachner

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Tenascin-C (TNC), a major component of the extracellular matrix, is strongly upregulated after injuries of the central nervous system (CNS) but its role in tissue repair is not understood. Both regeneration promoting and inhibiting roles of TNC have been proposed considering its abilities to both support and restrict neurite outgrowth in vitro. Here, we show that spontaneous recovery of locomotor functions after spinal cord injury is impaired in adult TNC-deficient (TNC -/-) mice in comparison to wild-type (TNC /) mice. The impaired recovery was associated with attenuated excitability of the plantar Hoffmann reflex (H-reflex), reduced glutamatergic input, reduced sprouting of monaminergic axons in the lumbar spinal cord and enhanced post-traumatic degeneration of corticospinal axons. The degeneration of corticospinal axons in TNC -/- mice was normalized to TNC / levels by application of the alternatively spliced TNC fibronectin type III homologous domain D (fnD). Finally, overexpression of TNC-fnD via adeno-associated virus in wild-type mice improved locomotor recovery, increased monaminergic axons sprouting, and reduced lesion scar volume after spinal cord injury. The functional efficacy of the viral-mediated TNC indicates a potentially useful approach for treatment of spinal cord injury.

Original languageEnglish (US)
Pages (from-to)1769-1777
Number of pages9
JournalMolecular Therapy
Volume18
Issue number10
DOIs
StatePublished - Oct 2010

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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