Sphingolipids and microRNA Changes in Blood following Blast Traumatic Brain Injury: An Exploratory Study

J Neurotrauma. 2018 Jan 15;35(2):353-361. doi: 10.1089/neu.2017.5009. Epub 2017 Nov 17.

Abstract

At present, accurate and reliable biomarkers to ascertain the presence, severity, or prognosis of blast traumatic brain injury (bTBI) are lacking. There is an urgent need to establish accurate and reliable biomarkers capable of mbTBI detection. Currently, there are no studies that identify changes in miRNA and lipids at varied severities of bTBI. Various biological components such as lipids, circulating mRNA, and miRNA, could potentially be detected using advanced techniques such as next-generation sequencing and mass spectroscopy. Therefore, plasma analysis is an attractive approach with which to diagnose and treat brain injuries. Subacute changes in plasma microRNA (miRNA) and lipid composition for sphingolipids were evaluated in a murine model of mild-to-moderate bTBI using next-generation sequencing and mass spectroscopy respectively. Animals were exposed at 17, 17 × 3, and 20 psi blast intensities using a calibrated blast simulator. Plasma lipid profiling demonstrated decreased C18 fatty acid chains of sphingomyelins and increased ceramide levels when compared with controls. Plasma levels of brain-enriched miRNA, miR-127 were increased in all groups while let-7a, b, and g were reduced in the 17 × 3 and 20 psi groups, but let 7d was increased in the 17 psi group. The majority of the miRs and lipids are highly conserved across different species, making them attractive to explore and potentially employ as diagnostic markers. It is tempting to speculate that sphingolipids, miR-128, and the let-7 family could predict mTBI, while a combination of miR-484, miR-122, miR-148a, miR-130a, and miR-223 could be used to predict the overall status of injury following blast injury.

Keywords: blast; ceramides; miRNA; sphingolipids.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biomarkers / blood*
  • Blast Injuries / blood*
  • Blast Injuries / diagnosis
  • Brain Injuries, Traumatic / blood*
  • Brain Injuries, Traumatic / diagnosis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / blood*
  • Sphingolipids / blood*

Substances

  • Biomarkers
  • MicroRNAs
  • Sphingolipids