Traumatic brain injury metabolome and mitochondrial impact after early stage Ru360 treatment

Mitochondrion. 2021 Mar:57:192-204. doi: 10.1016/j.mito.2021.01.003. Epub 2021 Jan 21.

Abstract

Ru360, a mitochondrial Ca2+ uptake inhibitor, was tested in a unilateral fluid percussion TBI model in developing rats (P31). Vehicle and Ru360 treated TBI rats underwent sensorimotor behavioral monitoring between 24 and 72 h, thereafter which 185 brain metabolites were analyzed postmortem using LC/MS. Ru360 treatment after TBI improved sensorimotor behavioral recovery, upregulated glycolytic and pentose phosphate pathways, mitigated oxidative stress and prevented NAD+ depletion across both hemispheres. While neural viability improved ipsilaterally, it reduced contralaterally. Ru360 treatment, overall, had a global impact with most benefit near the strongest injury impact areas, while perturbing mitochondrial oxidative energetics in the milder TBI impact areas.

Keywords: Calcium uniporter; Metabolomics; Mitochondria; Oxidative stress; Ru360; Traumatic brain injury.

Publication types

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

MeSH terms

  • Animals
  • Brain Injuries, Traumatic / drug therapy*
  • Brain Injuries, Traumatic / metabolism
  • Brain Injuries, Traumatic / psychology
  • Chromatography, Liquid
  • Disease Models, Animal
  • Energy Metabolism / drug effects
  • Glycolysis / drug effects
  • Male
  • Mass Spectrometry
  • Metabolomics / methods*
  • Mitochondria / metabolism*
  • Pentose Phosphate Pathway / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Ruthenium Compounds / administration & dosage*
  • Ruthenium Compounds / pharmacology

Substances

  • Reactive Oxygen Species
  • Ru 360
  • Ruthenium Compounds