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Role of lysophosphatidic acid in traumatic brain injury: anti‐LPA antibodies are neuroprotective after experimental TBI (999.3)
Author(s) -
Wojciak Jonathan,
Sabbadini Roger,
Crack Peter,
MorgantiKossmann Cristina,
Zhang Moses,
Pebay Alice,
Conquest Alison,
Morris Andrew
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.999.3
Subject(s) - lysophosphatidic acid , traumatic brain injury , neuroprotection , medicine , downregulation and upregulation , autotaxin , biomarker , brain damage , inflammation , receptor , biology , biochemistry , psychiatry , gene
Lysophosphatidic acid (LPA) is a bioactive phospholipid with a potentially causative role in neurotrauma. LPA receptors are increased after human brain injury and LPA levels are upregulated in the CSF and blood of traumatic brain injury (TBI) patients. Further, LPA levels correlated with initial injury severity using GCS, GOSE and ISS clinical assessments. Blocking LPA signaling with the LPA‐directed monoclonal antibody, B3/Lpathomab, was neuroprotective in a mouse controlled cortical impact model of TBI. B3 significantly reduced lesion volume measured both by standard histological assessments and MRI. Diminished tissue damage coincided with improvement in functional outcomes. B3 was anti‐inflammatory by limiting cerebral mRNA expression of pro‐inflammatory cytokines such as interleukin‐1b. These data strongly suggest that LPA dysregulation/upregulation is causal to injury progression following TBI, and that interventions to reduce LPA may have a significant impact in mitigating early and late phases of neurotrauma. We propose that anti‐LPA mAbs could satisfy a critical unmet need by limiting the initial neuronal damage and inflammatory processes while subsequently stimulating regenerative processes to optimize long‐term functional outcomes after neurotrauma. Importantly, LPA may also be a novel biomarker for TBI. Grant Funding Source : Lpath, Inc.