title: Gas Cluster Ion Beam Time-of-Flight Secondary Ion Mass Spectrometry High-Resolution Imaging of Cardiolipin Speciation in the Brain: Identification of Molecular Losses after Traumatic Injury.
abstract: Gas cluster ion beam-secondary ion mass spectrometry (GCIB-SIMS) has shown the full potential of mapping intact lipids in biological systems with better than 10 μm lateral resolution. This study investigated further the capability of GCIB-SIMS in imaging high-mass signals from intact cardiolipin (CL) and gangliosides in normal brain and the effect of a controlled cortical impact model (CCI) of traumatic brain injury (TBI) on their distribution. A combination of enzymatic and chemical treatments was employed to suppress the signals from the most abundant phospholipids (phosphatidylcholine (PC) and phosphatidylethanolamine (PE)) and enhance the signals from the low-abundance CLs and gangliosides to allow their GCIB-SIMS detection at 8 and 16 μm spatial resolution. Brain CLs have not been observed previously using other contemporary imaging mass spectrometry techniques at better than 50 μm spatial resolution. High-resolution images of naive and injured brain tissue facilitated the comparison of CL species across three multicell layers in the CA1, CA3, and DG regions of the hippocampus. GCIB-SIMS also reliably mapped losses of oxidizable polyunsaturated CL species (but not the oxidation-resistant saturated and monounsaturated gangliosides) to regions including the CA1 and CA3 of the hippocampus after CCI. This work extends the detection range for SIMS measurements of intact lipids to above m/z 2000, bridging the mass range gap compared with MALDI. Further advances in high-resolution SIMS of CLs, with the potential for single cell or supra-cellular imaging, will be essential for the understanding of CL's functional and structural organization in normal and injured brain.
authors.affiliation: Department of Chemistry, Pennsylvania State University , State College, Pennsylvania 16802, United States.
authors.forename: Hua
authors.identifier: 0000-0002-3598-0219
authors.initials: H
authors.lastname: Tian
authors.affiliation: Department of Environmental and Occupational Health, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.|Center for Free Radical and Antioxidant Health, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Louis J
authors.identifier: 0000-0001-6347-8448
authors.initials: LJ
authors.lastname: Sparvero
authors.affiliation: Department of Environmental and Occupational Health, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.|Center for Free Radical and Antioxidant Health, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Amoscato
authors.affiliation: Department of Chemistry, Pennsylvania State University , State College, Pennsylvania 16802, United States.
authors.forename: Anna
authors.initials: A
authors.lastname: Bloom
authors.affiliation: Department of Environmental and Occupational Health, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.|Center for Free Radical and Antioxidant Health, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.|Department of Critical Care Medicine, and Safar Center for Resuscitation Research, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Hülya
authors.initials: H
authors.lastname: Bayır
authors.affiliation: Department of Environmental and Occupational Health, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.|Departments of Chemistry, Pharmacology and Chemical Biology, Radiation Oncology, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.|Center for Free Radical and Antioxidant Health, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Valerian E
authors.identifier: 0000-0002-7245-1885
authors.initials: VE
authors.lastname: Kagan
authors.affiliation: Department of Chemistry, Pennsylvania State University , State College, Pennsylvania 16802, United States.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Winograd
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D002308:Cardiolipins / Q000378:metabolism*; D007094:Imides / Q000737:chemistry; D054020:Lasers, Gas; D008297:Male; D011437:Propylamines / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods*; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D002308:Cardiolipins; D007094:Imides; D011437:Propylamines; C000613388:1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride; D010738:Type C Phospholipases