title: Imaging mass spectrometry detects dynamic changes of phosphatidylcholine in rat hippocampal CA1 after transient global ischemia.
abstract: OBJECTIVE
  The initial steps in the cascade leading to cell death are still unknown because of the limitations of the existing methodology, strategy, and modalities used.
  
  
  METHODS
  Imaging mass spectrometry (IMS) was used to measure dynamic molecular changes of phosphatidylcholine (PC) species in the rat hippocampus after transient global ischemia (TGI) for 6min. Fresh frozen sections were obtained after euthanizing the rats on Days 1, 2, 4, 7, 10, 14, and 21. Histopathology and IMS of adjacent sections compared morphological and molecular changes, respectively.
  
  
  RESULTS
  Histopathological changes were absent immediately after TGI (at Day 1, superacute phase). At Days 2-21 after TGI (from subacute to chronic phases), histopathology revealed neuronal death associated with gliosis, inflammation, and accumulation of activated microglia in CA1. IMS detected significant molecular changes after TGI in the same CA1 domain: increase of PC (diacyl-16:0/22:6) in the superacute phase and increase of PC (diacyl-16:0/18:1) in the subacute to chronic phases.
  
  
  CONCLUSIONS
  Histopathology and IMS can provide comprehensive and complementary information on cell death mechanisms in the hippocampal CA1 after global ischemia. IMS provided novel data on molecular changes in phospholipids immediately after TGI. Increased level of PC (diacyl-16:0/22:6) in the pyramidal cell layer of hippocampal CA1 prior to the histopathological change may represent an early step in delayed neuronal death mechanisms.
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Miyawaki
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan. Electronic address: hiimai-nsu@umin.ac.jp.
authors.forename: H
authors.initials: H
authors.lastname: Imai
authors.affiliation: Health Innovation & Technology Center, Faculty of Health Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hayasaka
authors.affiliation: Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Masaki
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ono
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ochi
authors.affiliation: Department of Neurosurgery, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ito
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakatomi
authors.affiliation: Department of Cell Biology and Anatomy, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Setou
authors.affiliation: Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Saito
mesh_terms: D000208:Acute Disease; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D056547:CA1 Region, Hippocampal / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000502:physiology; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D005911:Gliosis / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D010713:Phosphatidylcholines / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D010713:Phosphatidylcholines
keywords: delayed neuronal cell death; hippocampus; imaging mass spectrometry; phosphatidylcholine