Abstract
BackgroundLysophosphatidic 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.FindingsHere 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.ConclusionsThis study presents a novel therapeutic approach for the treatment of TBI by blocking extracellular LPA signaling to minimize secondary brain damage and neurological dysfunction.
Highlights
Lysophosphatidic acid (LPA) is a bioactive phospholipid with a potentially causative role in neurotrauma
Using a mouse hemi-section model of spinal cord injury (SCI), we recently demonstrated that LPA is causally involved in the outcome of injury in that blocking its signaling via treatment with the specific anti-LPA monoclonal antibody, B3, limited glial scar formation, improved neuronal survival, promoted neurite sprouting and improved motor function [5]
This study provides the first evidence that therapeutic anti-LPA monoclonal antibody (mAb) could be useful in treating traumatic brain injury (TBI)-associated secondary damage
Summary
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. The primary injury can be focal or diffuse and initially produces hemorrhage and axonal injury followed by secondary effects such as edema and ischemia arising from the activation of biochemical pathways including inflammation, cell death and gliosis [1]. The role of LPA signaling in development has been described in detail, recent data suggest an involvement of LPA in neurotrauma [2] This is corroborated by compelling evidence from our group showing upregulation of LPA receptors following. Using a mouse hemi-section model of spinal cord injury (SCI), we recently demonstrated that LPA is causally involved in the outcome of injury in that blocking its signaling via treatment with the specific anti-LPA monoclonal antibody (mAb), B3, limited glial scar formation, improved neuronal survival, promoted neurite sprouting and improved motor function [5]. This study provides the first evidence that therapeutic anti-LPA mAbs could be useful in treating TBI-associated secondary damage
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