201. Blockage of lysophosphatidic acid signaling improves spinal cord injury outcomes.
- Author
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Goldshmit Y, Matteo R, Sztal T, Ellett F, Frisca F, Moreno K, Crombie D, Lieschke GJ, Currie PD, Sabbadini RA, and Pébay A
- Subjects
- Animals, Antibodies, Monoclonal pharmacology, Apoptosis drug effects, CHO Cells, Cell Death drug effects, Cell Proliferation drug effects, Cell Survival drug effects, Cricetinae, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Humans, Inflammation complications, Inflammation pathology, Lysophospholipids metabolism, Lysophospholipids pharmacology, Mice, Microglia drug effects, Microglia pathology, Motor Activity drug effects, Neurites drug effects, Neurites metabolism, Neuroprotective Agents pharmacology, Receptors, Lysophosphatidic Acid metabolism, Spinal Cord Injuries complications, Spinal Cord Injuries physiopathology, Zebrafish, Lysophospholipids antagonists & inhibitors, Recovery of Function drug effects, Signal Transduction drug effects, Spinal Cord Injuries pathology
- Abstract
Evidence suggests a proinflammatory role of lysophosphatidic acid (LPA) in various pathologic abnormalities, including in the central nervous system. Herein, we describe LPA as an important mediator of inflammation after spinal cord injury (SCI) in zebrafish and mice. Furthermore, we describe a novel monoclonal blocking antibody raised against LPA that potently inhibits LPA's effect in vitro and in vivo. This antibody, B3, specifically binds LPA, prevents it from interacting with its complement of receptors, and blocks LPA's effects on the neuronal differentiation of human neural stem/progenitor cells, demonstrating its specificity toward LPA signaling. When administered systemically to mice subjected to SCI, B3 substantially reduced glial inflammation and neuronal death. B3-treated animals demonstrated significantly more neuronal survival upstream of the lesion site, with some functional improvement. This study describes the use of anti-LPA monoclonal antibody as a novel therapeutic approach for the treatment of SCI., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2012
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