title: Inflammation Combined with Ischemia Produces Myelin Injury and Plaque-Like Aggregates of Myelin, Amyloid-β and AβPP in Adult Rat Brain.
abstract: BACKGROUND
  Ischemia, white matter injury, and Alzheimer's disease (AD) pathologies often co-exist in aging brain. How one condition predisposes to, interacts with, or perhaps causes the others remains unclear.
  
  
  OBJECTIVE
  To better understand the link between ischemia, white matter injury, and AD, adult rats were administered lipopolysaccharide (LPS) to serve as an inflammatory stimulus, and 24 h later subjected to 20-min focal cerebral ischemia (IS) followed by 30-min hypoxia (H).
  
  
  METHODS
  Myelin and axonal damage, as well as amyloid-β (Aβ) and amyloid-β protein precursor (AβPP) deposition were examined by Western blot and immunocytochemistry following LPS/IS/H. Findings were compared to the 5XFAD mouse AD brain.
  
  
  RESULTS
  Myelin/axonal injury was observed bilaterally in cortex following LPS/IS/H, along with an increase in IL-1, granzyme B, and LPS. AβPP deposition was present in ischemic striatum in regions of myelin loss. Aβ(1-42) and AβPP were deposited in small foci in ischemic cortex that co-localized with myelin aggregates. In the 5XFAD mouse AD model, cortical amyloid plaques also co-localized with myelin aggregates.
  
  
  CONCLUSIONS
  LPS/IS/H produce myelin injury and plaque-like aggregates of myelin. AβPP and Aβ co-localize with these myelin aggregates.
authors: Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA, USA.
authors: Xinhua
authors: X
authors: Zhan
authors: Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA, USA.
authors: Christopher
authors: C
authors: Cox
authors: Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA, USA.
authors: Bradley P
authors: BP
authors: Ander
authors: Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA, USA.
authors: Dazhi
authors: D
authors: Liu
authors: Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA, USA.
authors: Boryana
authors: B
authors: Stamova
authors: Alzheimer's Disease Center, University of California at Davis, Sacramento, CA, USA.|Department of Pathology and Laboratory Medicine, University of California at Davis, Sacramento, CA, USA.
authors: Lee-Way
authors: LW
authors: Jin
authors: Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA, USA.
authors: Glen C
authors: GC
authors: Jickling
authors: Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA, USA.
authors: Frank R
authors: FR
authors: Sharp
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000473:pathology; D002545:Brain Ischemia / Q000139:chemically induced*; D004195:Disease Models, Animal; D007249:Inflammation / Q000473:pathology; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000378:metabolism*; D009186:Myelin Sheath / Q000473:pathology*; D010446:Peptide Fragments / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008070:Lipopolysaccharides; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer’s disease; amyloid plaques; amyloid-β; amyloid-β protein precursor; hypoxia; lipopolysaccharide; myelin; myelin basic protein