The role of peroxisome proliferator-activated receptor γ, and effects of its agonist, rosiglitazone, on transient cerebral ischemic damage.
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.
Lee
Choong Hyun
CH
Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea.
Park
Ok Kyu
OK
Yoo
Ki-Yeon
KY
Byun
Kyunghee
K
Lee
Bonghee
B
Choi
Jung Hoon
JH
Hwang
In Koo
IK
Kim
Young-Myeong
YM
Won
Moo-Ho
MH
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*
D018793:Interleukin-13; D018696:Neuroprotective Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D015847:Interleukin-4