Matrix-Assisted Laser Desorption Ionization Mapping of Lysophosphatidic Acid Changes after Traumatic Brain Injury and the Relationship to Cellular Pathology

Abstract

Lysophosphatidic acid (LPA) levels increase in the cerebrospinal fluid and blood within 24 hours after traumatic brain injury (TBI), indicating it may be a biomarker for subsequent cellular pathology. However, no data exist that document this association after TBI. We, therefore, acquired matrix-assisted laser desorption ionization imaging mass spectrometry data of LPA, major LPA metabolites, and hemoglobin from adult rat brains at 1 and 3 hours after controlled cortical impact injury. Data were semiquantitatively assessed by signal intensity analysis normalized to naïve rat brains acquired concurrently. Gray and white matter pathology was assessed on adjacent sections using immunohistochemistry for cell death, axonal injury, and intracellular LPA, to determine the spatiotemporal patterning of LPA corresponding to pathology. The results revealed significant increases in LPA and LPA precursors at 1 hour after injury and robust enhancement in LPA diffusively throughout the brain at 3 hours after injury. Voxel-wise analysis of LPA by matrix-assisted laser desorption ionization and β-amyloid precursor protein by immunohistochemistry in adjacent sections showed significant association, raising the possibility that LPA is linked to secondary axonal injury. Total LPA and metabolites were also present in remotely injured areas, including cerebellum and brain stem, and in particular thalamus, where intracellular LPA is associated with cell death. LPA may be a useful biomarker of cellular pathology after TBI.

Association of lysophosphatidic acids with cerebrospinal fluid biomarkers and progression to Alzheimer’s disease

“…LPAs are a bioactive component of oxLDL, which show a positive correlation with CSF levels of Aβ [48]. Moreover, traumatic brain injury (TBI) patients also exhibit increased CSF levels of LPAs [49]. Because amyloid pathology is observed in nearly 30% of TBI patients with unknown mechanisms [50], our observed positive association of amyloid pathology and LPA may suggest the role of LPAs as a mediator in the aggregation of amyloid pathology, which needs further investigation.…”

Role of lysophosphatidic acid and its receptors in health and disease: novel therapeutic strategies

“… 160 Using a rat model of neurotrauma, Mcdonald and coworkers demonstrated that LPA increases diffusely after the injury, whereas LPA metabolites increases in white matter, in the hemorrhagic pericontused gray matter regions both LPA and its metabolites were increased, these events results in axonal injury and cell death, especially in the white matter. 161 …”

“…In patients, LPA levels increases in the blood and CSF within 24 h in TBI patients, indicating that LPA could possibly be one of the first mediators responding to the injury and suggesting it may be a biomarker for subsequent cellular pathology. 161 …”

Co-Expression Network Analysis of MicroRNAs and Proteins in Severe Traumatic Brain Injury: A Systematic Review

“…The same search filters were applied, leading to 295 results being excluded while a further 71 duplicates were removed using EndNote 20 [ 30 ]. A total of 140 papers were manually excluded following assessment against the selection criteria, leaving a total of 24 papers eligible for inclusion in the review [ 36 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ]. Figure 2 provides an overview of the protein literature search and study selection process.…”