Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes

Journal of Neuroinflammation

Alice Pébay²  Roger A Sabbadini⁶  Robert L Medcalf³  Leigh A Johnston⁴  Maria Daglas³  Alison Conquest²  Yona Goldshmit²  Maithili Sashindranath³  David Wright¹  Ila Karve⁸  Jonathan K Fleming⁶  Jonathan M Wojciak⁶  Andrew J Morris⁵  Maria Cristina Morganti-Kossmann⁷  Moses Zhang⁸  Peter J Crack⁸ 

[1] Department of Anatomy and Neuroscience, the University of Melbourne, Parkville, Australia;Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital & Department of Ophthalmology, the University of Melbourne, East Melbourne, Australia;Australian Centre for Blood Diseases, Monash University, Melbourne, Australia;Florey Institute of Neuroscience and Mental Health, Parkville, Australia;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;Barrow Neurological Institute, Department of Child Health, Phoenix Children’s Hospital, University of Arizona, Phoenix, AZ, USA;Department of Pharmacology, the University of Melbourne, Parkville, Australia

关键词: IL-6;    Anti-LPA antibody;    Magnetic resonance imaging;    Control cortical impact;    Human cerebrospinal fluid;    Traumatic brain injury;    Lysophosphatidic acid;   

Others  :  824076
DOI  :  10.1186/1742-2094-11-37

 received in 2014-01-06, accepted in 2014-02-16,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Crack et al.; licensee BioMed Central Ltd.

【 图 表 】

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