title: Peroxisomal biogenesis in ischemic brain.
abstract: OBJECTIVE
  Peroxisomes are highly adaptable and dynamic organelles, adjusting their size, number, and enzyme composition to changing environmental and metabolic demands. We determined whether peroxisomes respond to ischemia, and whether peroxisomal biogenesis is an adaptive response to cerebral ischemia.
  
  
  RESULTS
  Focal cerebral ischemia induced peroxisomal biogenesis in peri-infarct neurons, which was associated with a corresponding increase in peroxisomal antioxidant enzyme catalase. Peroxisomal biogenesis was also observed in primary cultured cortical neurons subjected to ischemic insult induced by oxygen-glucose deprivation (OGD). A catalase inhibitor increased OGD-induced neuronal death. Moreover, preventing peroxisomal proliferation by knocking down dynamin-related protein 1 (Drp1) exacerbated neuronal death induced by OGD, whereas enhancing peroxisomal biogenesis pharmacologically using a peroxisome proliferator-activated receptor-alpha agonist protected against neuronal death induced by OGD.
  
  
  METHODS
  This is the first documentation of ischemia-induced peroxisomal biogenesis in mammalian brain using a combined in vivo and in vitro approach, electron microscopy, high-resolution laser-scanning confocal microscopy, and super-resolution structured illumination microscopy.
  
  
  CONCLUSIONS
  Our findings suggest that neurons respond to ischemic injury by increasing peroxisome biogenesis, which serves a protective function, likely mediated by enhanced antioxidant capacity of neurons.
authors.affiliation: 1 Department of Anesthesiology & Perioperative Medicine, The Knight Cardiovascular Institute, Oregon Health & Science University , Portland, Oregon.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Young
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Nelson
authors.forename: Jian
authors.initials: J
authors.lastname: Cheng
authors.forename: Wenri
authors.initials: W
authors.lastname: Zhang
authors.forename: Sarah
authors.initials: S
authors.lastname: Mader
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Davis
authors.forename: Richard S
authors.initials: RS
authors.lastname: Morrison
authors.forename: Nabil J
authors.initials: NJ
authors.lastname: Alkayed
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism*; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D034281:Dynamins / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D010100:Oxygen / Q000378:metabolism
chemical_list: D002374:Catalase; C486391:Dnm1l protein, mouse; D034281:Dynamins; D005947:Glucose; D010100:Oxygen