Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes

Persistent Link:
http://hdl.handle.net/10150/610194
Title:
Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes
Author:
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
Affiliation:
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
Issue Date:
2014
Publisher:
BioMed Central
Citation:
Crack et al. Journal of Neuroinflammation 2014, 11:37 http://www.jneuroinflammation.com/content/11/1/37
Journal:
Journal of Neuroinflammation
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)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
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.
EISSN:
1742-2094
DOI:
10.1186/1742-2094-11-37
Keywords:
Lysophosphatidic acid; Traumatic brain injury; Human cerebrospinal fluid; Control cortical impact; Magnetic resonance imaging; Anti-LPA antibody; IL-6
Version:
Final published version
Additional Links:
http://www.jneuroinflammation.com/content/11/1/37

Full metadata record

DC FieldValue Language
dc.contributor.authorCrack, Peteren
dc.contributor.authorZhang, Mosesen
dc.contributor.authorMorganti-Kossmann, Mariaen
dc.contributor.authorMorris, Andrewen
dc.contributor.authorWojciak, Jonathanen
dc.contributor.authorFleming, Jonathanen
dc.contributor.authorKarve, Ilaen
dc.contributor.authorWright, Daviden
dc.contributor.authorSashindranath, Maithilien
dc.contributor.authorGoldshmit, Yonaen
dc.contributor.authorConquest, Alisonen
dc.contributor.authorDaglas, Mariaen
dc.contributor.authorJohnston, Leighen
dc.contributor.authorMedcalf, Roberten
dc.contributor.authorSabbadini, Rogeren
dc.contributor.authorPebay, Aliceen
dc.date.accessioned2016-05-20T09:00:45Z-
dc.date.available2016-05-20T09:00:45Z-
dc.date.issued2014en
dc.identifier.citationCrack et al. Journal of Neuroinflammation 2014, 11:37 http://www.jneuroinflammation.com/content/11/1/37en
dc.identifier.doi10.1186/1742-2094-11-37en
dc.identifier.urihttp://hdl.handle.net/10150/610194-
dc.description.abstractBACKGROUND: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.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.jneuroinflammation.com/content/11/1/37en
dc.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)en
dc.subjectLysophosphatidic aciden
dc.subjectTraumatic brain injuryen
dc.subjectHuman cerebrospinal fluiden
dc.subjectControl cortical impacten
dc.subjectMagnetic resonance imagingen
dc.subjectAnti-LPA antibodyen
dc.subjectIL-6en
dc.titleAnti-lysophosphatidic acid antibodies improve traumatic brain injury outcomesen
dc.typeArticleen
dc.identifier.eissn1742-2094en
dc.contributor.departmentDepartment of Pharmacology, the University of Melbourne, Parkville, Australiaen
dc.contributor.departmentDepartment of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australiaen
dc.contributor.departmentBarrow Neurological Institute, Department of Child Health, Phoenix Children’s Hospital, University of Arizona, Phoenix, AZ, USAen
dc.contributor.departmentDivision of Cardiovascular Medicine, University of Kentucky College of Medicine, Lexington, KY, USAen
dc.contributor.departmentDepartment of Biology, San Diego State University and Lpath Inc, 4025 Sorrento Valley Blvd, San Diego, CA, USAen
dc.contributor.departmentFlorey Institute of Neuroscience and Mental Health, Parkville, Australiaen
dc.contributor.departmentDepartment of Anatomy and Neuroscience, the University of Melbourne, Parkville, Australiaen
dc.contributor.departmentAustralian Centre for Blood Diseases, Monash University, Melbourne, Australiaen
dc.contributor.departmentCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital & Department of Ophthalmology, the University of Melbourne, East Melbourne, Australiaen
dc.contributor.departmentAustralian Regenerative Medicine Institute, Monash University, Clayton, Australiaen
dc.contributor.departmentNational Trauma Research Institute, Alfred Hospital & Monash University, Melbourne, Australiaen
dc.contributor.departmentNeuroengineering Laboratory, Department of Electrical and Electronic Engineering, the University of Melbourne, Parkville, Australiaen
dc.identifier.journalJournal of Neuroinflammationen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.