title: Anti-lysophosphatidic acid antibodies improve traumatic brain injury outcomes.
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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Pharmacology, the University of Melbourne, Parkville, Australia. pcrack@unimelb.edu.au.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Crack
authors.forename: Moses
authors.initials: M
authors.lastname: Zhang
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Morganti-Kossmann
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Morris
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Wojciak
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Fleming
authors.forename: Ila
authors.initials: I
authors.lastname: Karve
authors.forename: David
authors.initials: D
authors.lastname: Wright
authors.forename: Maithili
authors.initials: M
authors.lastname: Sashindranath
authors.forename: Yona
authors.initials: Y
authors.lastname: Goldshmit
authors.forename: Alison
authors.initials: A
authors.lastname: Conquest
authors.forename: Maria
authors.initials: M
authors.lastname: Daglas
authors.forename: Leigh A
authors.initials: LA
authors.lastname: Johnston
authors.forename: Robert L
authors.initials: RL
authors.lastname: Medcalf
authors.forename: Roger A
authors.initials: RA
authors.lastname: Sabbadini
authors.forename: Alice
authors.initials: A
authors.lastname: Pébay
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D000818:Animals; D001930:Brain Injuries / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D008246:Lysophospholipids / Q000134:cerebrospinal fluid / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D007155:Immunologic Factors; D008246:Lysophospholipids; C032881:lysophosphatidic acid