title: A peroxisome proliferator-activated receptor-gamma agonist reduces infarct size in transient but not in permanent ischemia.
abstract: OBJECTIVE
  Activators of peroxisome proliferator-activated receptor-gamma (PPARgamma), a member of the PPAR family, increase levels of CuZn-superoxide dismutase (SOD) in cultured endothelium, suggesting a mechanism by which it may exert its protective effect within the brain. These properties raise the question of whether a PPARgamma agonist may be neuroprotective in models of ischemia without reperfusion, in which oxidative injury is less prevalent.
  
  
  METHODS
  In 2 groups of rats, 90 minutes of middle cerebral artery (MCA) occlusion was followed by 1 day of reperfusion, with 1 group receiving pioglitazone (a PPARgamma agonist) starting 72 hours before MCA occlusion (MCAO) and continuing through the day of occlusion, whereas the other group received vehicle only. In 2 comparable groups, the MCA was occluded permanently. One day after occlusion, the animals were tested neurologically and infarct volumes were calculated. In a separate group, rats were treated with pioglitazone or vehicle for 4 days. Tissue was obtained from the cortex and the striatum 2 hours into reperfusion after 90 minutes of MCAO, and the tissue was examined for CuZn-SOD by Western blot.
  
  
  RESULTS
  Results show a significant reduction in infarct size in the treated rats, with transient MCAO but not permanent MCAO. There was also an improvement in neurological score in the treated animals after transient MCAO. The level of CuZn-SOD was increased in the cortex in treated animals.
  
  
  CONCLUSIONS
  These data, which show that a PPARgamma agonist reduces infarct size in transient but not permanent MCAO, suggest that the role of PPARgamma is specific to events occurring during reperfusion. Our data point to CuZn-SOD as the mediator of this neuroprotection.
authors.affiliation: Cerebrovascular Research Center, Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia 19104-6063, USA.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Shimazu
authors.forename: Ikuo
authors.initials: I
authors.lastname: Inoue
authors.forename: Nobuo
authors.initials: N
authors.lastname: Araki
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Asano
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sawada
authors.forename: Daisuke
authors.initials: D
authors.lastname: Furuya
authors.forename: Harumitsu
authors.initials: H
authors.lastname: Nagoya
authors.forename: Joel H
authors.initials: JH
authors.lastname: Greenberg
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D015153:Blotting, Western; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology*; D002560:Cerebrovascular Circulation; D004727:Endothelium / Q000201:enzymology*; D006863:Hydrogen-Ion Concentration; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D047495:PPAR gamma / Q000819:agonists / Q000502:physiology*; D000077205:Pioglitazone; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D015427:Reperfusion Injury; D013482:Superoxide Dismutase / Q000502:physiology*; D045162:Thiazolidinediones / Q000494:pharmacology; D013997:Time Factors
chemical_list: D047495:PPAR gamma; D045162:Thiazolidinediones; D013482:Superoxide Dismutase; D000077205:Pioglitazone