Neutralization of the chemokine CXCL10 enhances tissue sparing and angiogenesis following spinal cord injury.
After spinal cord injury, there is a chemoattractant-mediated inflammatory response that is associated with secondary degeneration. The chemoattractant CXCL10 recruits CD4 Th1 cells via the CXCR3A receptor and inhibits growth and chemotaxis of endothelial cells via the CXCR3B receptor. To test the hypothesis that CXCL10 inhibits angiogenesis following spinal cord injury, we assayed the brainstems and spinal cords of spinal cord-injured mice treated with anti-CXCL10 antibodies for expression of angiogenesis-associated genes and quantified blood vessels within their spinal cords. Brainstem microarray analysis indicated eight angiogenesis-associated genes that had significantly higher expression levels in the treated mice than in the untreated mice. Ribonuclease protection assays of the spinal cords showed a significant increase in eight angiogenesis-associated genes in treated animals compared with untreated animals. Histological analysis of the spinal cords of treated and untreated mice showed a significant increase in the number of blood vessels in treated animals. We conclude that CXCL10 plays a critical role in vasculature remodeling following spinal cord injury and that angiogenesis is enhanced following anti-CXCL10 treatment of spinal cord injuries. Improved blood flow and oxygen supply to the injury site may contribute to the functional improvement associated with this treatment.
Glaser
Janette
J
Department of Anatomy and Neurobiology, Reeve-Irvine Research Center, University of California at Irvine, Irvine, California 92697, USA.
Gonzalez
Rafael
R
Perreau
Victoria M
VM
Cotman
Carl W
CW
Keirstead
Hans S
HS
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D001808:Blood Vessels / Q000378:metabolism; D001933:Brain Stem / Q000378:metabolism; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology*; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics; D014945:Wound Healing / Q000502:physiology*
D000906:Antibodies; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D019408:Platelet Endothelial Cell Adhesion Molecule-1