title: The role of peroxisome proliferator-activated receptor γ, and effects of its agonist, rosiglitazone, on transient cerebral ischemic damage.
abstract: Peroxisome proliferator-activated receptor γ (PPARγ) is expressed in neurons and glia, and its synthetic agonist, rosiglitazone (RSG), regulates inflammatory process and has neuroprotective effects against neurological disorders. In the present study, we examined the role of PPARγ in the hippocampal CA1 region (CA1) after transient cerebral ischemia and the neuroprotective effects of RSG on ischemic damage. RSG attenuated neuronal damage in the ischemic CA1, not showing perfect neuroprotection: the RSG appeared to delay neuronal death after ischemia/reperfusion (I/R). PPARγ immunoreactivity and protein levels were increased after I/R, and most of PPARγ-immunoreactive cells colocalized with microglia, not astrocytes. In addition, RSG attenuated glial activation and increased IL-4 and IL-13 levels in the ischemic CA1. These results indicate that PPARγ increases and expresses in microglia after I/R, and that RSG delays neuronal damage by interfering with glial activations and increases anti-inflammatory cytokines in response to ischemic damage.
authors.affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Choong Hyun
authors.initials: CH
authors.lastname: Lee
authors.forename: Ok Kyu
authors.initials: OK
authors.lastname: Park
authors.forename: Ki-Yeon
authors.initials: KY
authors.lastname: Yoo
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Byun
authors.forename: Bonghee
authors.initials: B
authors.lastname: Lee
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Choi
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000502:physiology; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D005849:Gerbillinae; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000502:physiology; D009410:Nerve Degeneration / Q000188:drug therapy / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism / Q000502:physiology*; D015424:Reperfusion; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018793:Interleukin-13; D018696:Neuroprotective Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D015847:Interleukin-4