Reducing inflammation decreases secondary degeneration and functional deficit after spinal cord injury.
Injury to the spinal cord is followed by degeneration, which leads to progressive tissue loss and usually cystic cavitation. Cellular and humoral immune responses have been implicated as mediators of secondary degeneration, and the expression of leukocyte chemoattractants has been shown to precede immune cell influx. However, the relationship between the increased expression of chemoattractants, the invasion of lymphocytes, and overall lesion evolution is poorly understood. Here, we show that the T-lymphocyte chemoattractant CXCL10 is upregulated after dorsal hemisection injury to the adult mammalian spinal cord of C57/BL6 mice, and that antibody neutralization of CXCL10 beginning 1 day prior to injury dramatically reduces the T-lymphocyte invasion that normally occurs after trauma. Notably, this treatment resulted in a significant reduction of secondary tissue loss and functional deficit. We conclude that CXCL10 plays a critical role in recruitment of T lymphocytes to sites of spinal cord injury, and that a reduction of T-lymphocyte recruitment significantly enhances tissue preservation and functional outcome.
Gonzalez
Rafael
R
Reeve-Irvine Research Center, Department of Anatomy and Neurobiology, University of California at Irvine,2111 Gillespie Neuroscience Research Facility, Irvine, CA 92697-4292, USA.
Glaser
Janette
J
Liu
Michael T
MT
Lane
Thomas E
TE
Keirstead
Hans S
HS
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001696:Biomechanical Phenomena; D018791:CD4 Lymphocyte Count; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology*; D008124:Locomotion / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000502:physiology; D009410:Nerve Degeneration / Q000473:pathology* / Q000517:prevention & control*; D023282:Nuclease Protection Assays; D012333:RNA, Messenger / Q000096:biosynthesis; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology*; D013601:T-Lymphocytes / Q000502:physiology
D019138:Antibodies, Blocking; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D012333:RNA, Messenger