title: Imaging mass spectrometry reveals loss of polyunsaturated cardiolipins in the cortical contusion, hippocampus, and thalamus after traumatic brain injury.
abstract: Traumatic brain injury (TBI) leads to changes in ion fluxes, alterations in mitochondrial function, and increased generation of reactive oxygen species, resulting in secondary tissue damage. Mitochondria play important signaling roles in coordination of multiple metabolic platforms in addition to their well-known role in bioenergetics. Mitochondrial signaling strongly depends on cardiolipin (CL), a mitochondria-specific structurally unusual anionic phospholipid containing four fatty acyl chains. While our previous reports indicated that CL is selectively oxidized and presents itself as a target for the redox therapy following TBI, the topography of changes of CL in the injured brain remained to be defined. Here, we present a matrix-assisted laser desorption/ionization imaging study which reports regio-specific changes in CL, in a controlled cortical impact model of TBI in rats. Matrix-assisted laser desorption/ionization imaging revealed that TBI caused early decreases in CL in the contusional cortex, ipsilateral hippocampus, and thalamus with the most highly unsaturated CL species being most susceptible to loss. Phosphatidylinositol was the only other lipid species that exhibited a significant decrease, albeit to a lesser extent than CL. Signals for other lipids remained unchanged. This is the first study evaluating the spatial distribution of CL loss after acute brain injury. We propose that the CL loss may constitute an upstream mechanism for CL-driven signaling in different brain regions as an early response mechanism and may also underlie the bioenergetic changes that occur in hippocampal, cortical, and thalamic mitochondria after TBI.
authors: Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.|Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: Louis J
authors: 0000-0001-6347-8448
authors: LJ
authors: Sparvero
authors: Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.|Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: Andrew A
authors: AA
authors: Amoscato
authors: Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.|Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: Arthur B
authors: AB
authors: Fink
authors: Department of Critical Care Medicine, and Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: Tamil
authors: T
authors: Anthonymuthu
authors: Department of Critical Care Medicine, and Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: Lee Ann
authors: LA
authors: New
authors: Department of Critical Care Medicine, and Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: Patrick M
authors: PM
authors: Kochanek
authors: Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: Simon
authors: S
authors: Watkins
authors: Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.|Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: Valerian E
authors: VE
authors: Kagan
authors: Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.|Center for Free Radical and Antioxidant Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.|Department of Critical Care Medicine, and Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors: Hulya
authors: H
authors: Bayır
mesh_terms: D000818:Animals; D000070624:Brain Contusion / Q000000981:diagnostic imaging / Q000378:metabolism; D000070642:Brain Injuries, Traumatic / Q000000981:diagnostic imaging* / Q000378:metabolism; D002308:Cardiolipins / Q000378:metabolism; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism; D006624:Hippocampus / Q000000981:diagnostic imaging* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013788:Thalamus / Q000000981:diagnostic imaging* / Q000378:metabolism
chemical_list: D002308:Cardiolipins
keywords: cardiolipin; hippocampus; imaging mass spectrometry; lipids; thalamus; traumatic brain injury