Enhanced regeneration and functional recovery after spinal root avulsion by manipulation of the proteoglycan receptor PTPσ

Sci Rep. 2015 Oct 14;5:14923. doi: 10.1038/srep14923.

Abstract

Following root avulsion, spinal nerves are physically disconnected from the spinal cord. Severe motoneuron death and inefficient axon regeneration often result in devastating motor dysfunction. Newly formed axons need to extend through inhibitory scar tissue at the CNS-PNS transitional zone before entering into a pro-regenerative peripheral nerve trajectory. CSPGs are dominant suppressors in scar tissue and exert inhibition via neuronal receptors including PTPσ. Previously, a small peptide memetic of the PTPσ wedge region named ISP (Intracellular Sigma Peptide) was generated, and its capabilities to target PTPσ and relieve CSPG inhibition were validated. Here, we demonstrate that after ventral root avulsion and immediate re-implantation, modulation of PTPσ by systemic delivery of ISP remarkably enhanced regeneration. ISP treatment reduced motoneuron death, increased the number of axons regenerating across scar tissue, rebuilt healthy neuromuscular junctions and enhanced motor functional recovery. Our study shows that modulation of PTPσ is a potential therapeutic strategy for root avulsion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System Agents / administration & dosage
  • Dose-Response Relationship, Drug
  • Female
  • Intracellular Signaling Peptides and Proteins / administration & dosage*
  • Proteoglycans / metabolism
  • Radiculopathy / physiopathology*
  • Radiculopathy / therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / metabolism*
  • Recovery of Function / drug effects
  • Recovery of Function / physiology*
  • Spinal Cord Regeneration / drug effects
  • Spinal Cord Regeneration / physiology*
  • Spinal Nerve Roots / drug effects
  • Spinal Nerve Roots / physiopathology
  • Treatment Outcome

Substances

  • Central Nervous System Agents
  • Intracellular Signaling Peptides and Proteins
  • Proteoglycans
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2