Blockage of Lysophosphatidic Acid Signaling Improves Spinal Cord Injury Outcomes
- Authors
- Goldshmit, Y., Matteo, R., Sztal, T., Ellett, F., Frisca, F., Moreno, K., Crombie, D., Lieschke, G.J., Currie, P.D., Sabbadini, R.A., and Pebay, A.
- ID
- ZDB-PUB-120724-25
- Date
- 2012
- Source
- The American journal of pathology 181(3): 978-992 (Journal)
- Registered Authors
- Currie, Peter D., Ellett, Felix, Goldshmit, Yona, Lieschke, Graham J., Sztal, Tamar Esther
- Keywords
- none
- MeSH Terms
-
- 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/antagonists & inhibitors*
- 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
- Recovery of Function*/drug effects
- Signal Transduction*/drug effects
- Spinal Cord Injuries/complications
- Spinal Cord Injuries/pathology*
- Spinal Cord Injuries/physiopathology
- Zebrafish
- PubMed
- 22819724 Full text @ Am. J. Pathol.
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.