Neutralization of the chemokine CXCL10 reduces apoptosis and increases axon sprouting after spinal cord injury

✍ Scribed by Janette Glaser; Rafael Gonzalez; Ellika Sadr; Hans S. Keirstead

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 432 KB
• Volume: 84
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.20982

✦ Synopsis

Abstract

Spinal cord injury (SCI) is followed by a secondary degenerative process that includes cell death. We have previously demonstrated that the chemokine CXCL10 is up‐regulated following SCI and plays a critical role in T‐lymphocyte recruitment to sites of injury and inhibition of angiogenesis; antibody‐mediated functional blockade of CXCL10 reduced inflammation while enhancing angiogenesis. We hypothesized, based on these findings, that the injury environment established by anti‐CXCL10 antibody treatment would support greater survival of neurons and enhance axon sprouting compared with the untreated, injured spinal cord. Here, we document gene array and histopathological data to support our hypothesis. Gene array analysis of treated and untreated tissue from spinal cord‐injured animals revealed eight apoptosis‐related genes with significant expression changes at 3 days postinjury. In support of these data, quantification of TUNEL‐positive cells at 3 days postinjury indicated a 75% reduction in the number of dying cells in treated animals compared with untreated animals. Gene array analysis of treated and untreated tissue also revealed six central nervous system growth‐related genes with significant expression changes in the brainstem at 14 days postinjury. In support of these data, quantification of anterograde‐labeled corticospinal tract fibers indicated a 60–70% increase in axon sprouting caudal to the injury site in treated animals compared with untreated animals. These findings indicate that anti‐CXCL10 antibody treatment provides an environment that reduces apoptosis and increases axon sprouting following injury to the adult spinal cord. © 2006 Wiley‐Liss, Inc.