Therapeutic neutralization of CXCL10 decreases secondary degeneration and functional deficit after spinal cord injury in mice.
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.
Gonzalez
Rafael
R
University of California, Reeve Irvine Research Center, Department of Anatomy and Neurobiology, 2111 Gillespie Neuroscience Research Facility, College of Medicine, Irvine, CA 92697-4292, USA.
Hickey
Michelle J
MJ
Espinosa
Julio M
JM
Nistor
Gabriel
G
Lane
Thomas E
TE
Keirstead
Hans S
HS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C485433:Cxcl10 protein, mouse