Therapeutic neutralization of CXCL10 decreases secondary degeneration and functional deficit after spinal cord injury in mice

Regen Med. 2007 Sep;2(5):771-83. doi: 10.2217/17460751.2.5.771.

Abstract

Inflammation plays a critical role in the secondary degenerative response to spinal cord injury (SCI). The influx of inflammatory cells following SCI is preceded by the expression of specific chemoattractants, including chemokines. The chemokine CXCL10 is a potent T lymphocyte recruiter and has been strongly implicated in the pathology of many CNS disorders. We have previously demonstrated that CXCL10 exacerbates secondary degeneration by blocking the function of CXCL10 prior to SCI. Here we administered neutralizing antibodies against CXCL10 1 h after SCI in order to investigate the efficacy of this therapeutic intervention in abating histologic and functional deficit following acute SCI and further assess the functional role of CXCL10 in secondary degeneration. Neutralization of CXCL10 significantly reduced inflammation, apoptosis, neuronal loss and whole tissue loss. Notably, this therapeutic treatment also promoted revascularization of the injured spinal cord and functional recovery. These data suggest that anti-CXCL10 antibody treatment is a viable therapeutic strategy for acute SCI.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Apoptosis / drug effects
  • Chemokine CXCL10
  • Chemokines, CXC / genetics
  • Chemokines, CXC / immunology*
  • Chemokines, CXC / metabolism*
  • Female
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neurons / drug effects
  • Recovery of Function / drug effects
  • Recovery of Function / physiology*
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / physiopathology
  • Time Factors

Substances

  • Antibodies, Monoclonal
  • Chemokine CXCL10
  • Chemokines, CXC
  • Cxcl10 protein, mouse