BACKGROUND:Lysophosphatidic acid (LPA) is a bioactive phospholipid with a potentially causative role in neurotrauma. Blocking LPA signaling with the LPA-directed monoclonal antibody B3/Lpathomab is neuroprotective in the mouse spinal cord following injury.FINDINGS:Here we investigated the use of this agent in treatment of secondary brain damage consequent to traumatic brain injury (TBI). LPA was elevated in cerebrospinal fluid (CSF) of patients with TBI compared to controls. LPA levels were also elevated in a mouse controlled cortical impact (CCI) model of TBI and B3 significantly reduced lesion volume by both histological and MRI assessments. Diminished tissue damage coincided with lower brain IL-6 levels and improvement in functional outcomes.CONCLUSIONS:This study presents a novel therapeutic approach for the treatment of TBI by blocking extracellular LPA signaling to minimize secondary brain damage and neurological dysfunction.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/610194 |
| Date | January 2014 |
| Creators | Crack, Peter, Zhang, Moses, Morganti-Kossmann, Maria, Morris, Andrew, Wojciak, Jonathan, Fleming, Jonathan, Karve, Ila, Wright, David, Sashindranath, Maithili, Goldshmit, Yona, Conquest, Alison, Daglas, Maria, Johnston, Leigh, Medcalf, Robert, Sabbadini, Roger, Pebay, Alice |
| Contributors | Department of Pharmacology, the University of Melbourne, Parkville, Australia, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia, Barrow Neurological Institute, Department of Child Health, Phoenix Children’s Hospital, University of Arizona, Phoenix, AZ, USA, Division of Cardiovascular Medicine, University of Kentucky College of Medicine, Lexington, KY, USA, Department of Biology, San Diego State University and Lpath Inc, 4025 Sorrento Valley Blvd, San Diego, CA, USA, Florey Institute of Neuroscience and Mental Health, Parkville, Australia, Department of Anatomy and Neuroscience, the University of Melbourne, Parkville, Australia, Australian Centre for Blood Diseases, Monash University, Melbourne, Australia, Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital & Department of Ophthalmology, the University of Melbourne, East Melbourne, Australia, Australian Regenerative Medicine Institute, Monash University, Clayton, Australia, National Trauma Research Institute, Alfred Hospital & Monash University, Melbourne, Australia, Neuroengineering Laboratory, Department of Electrical and Electronic Engineering, the University of Melbourne, Parkville, Australia |
| Publisher | BioMed Central |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | Article |
| Rights | © 2014 Crack et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0) |
| Relation | http://www.jneuroinflammation.com/content/11/1/37 |
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