Activation of peroxisome proliferator-activated receptor β/δ attenuates acute ischemic stroke on middle cerebral ischemia occlusion in rats.
BACKGROUND
Peroxisome proliferator-activated receptor (PPAR)-β/δ is a transcription factor that belongs to the nuclear hormone receptor family. There is little information about the effects of the immediate administration of specific ligands of PPAR-β/δ (GW0742) in animal models of acute ischemic stroke. Using a rat model of middle cerebral ischemia occlusion (MCAO) in vivo, we have investigated the effect of pretreatment with GW0742 before MCAO.


METHODS
The neuroprotective effect of GW0742 against acute ischemic stroke was evaluated by the neurologic deficit score (NDS), dry-wet weight, and 2,3,5-triphenyltetrazolium chloride staining. The levels of interleukin (IL)-1β, nuclear factor (NF)-κB, and tumor necrosis factor (TNF)-α were detected by an enzyme-linked immunosorbent assay. The expressions of inducible nitric oxide synthase (iNOS), Bax, and Bcl-2 were detected by Western blot. The apoptotic cells were counted by in situ terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay.


RESULTS
The pretreatment with GW0742 significantly increased the expression of Bcl-2, and significantly decreased in the volume of infarction, NDS, edema, expressions of IL-1β, NF-κB, TNFα, and Bax, contents of iNOS and the apoptotic cells in infarct cerebral hemisphere compared with rats in the vehicle group at 24 hours after MCAO.


CONCLUSIONS
The study suggests the neuroprotective effect of the PPAR-β/δ ligand GW0742 in acute ischemic stroke by a mechanism that may involve its anti-inflammatory and antiapoptotic action.
Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an, China; Department of Neurosurgery, Urumqi General Hospital of PLA, Urumqi, China.
Xiaodong
X
Chao
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Chunlei
C
Xiong
Department of Cardiology, The First Hospital of PLA, Lanzhou, China.
Weifeng
W
Dong
Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Yan
Y
Qu
Department of Neurosurgery, People's Hospital of Jishan County, Shanxi, China.
Weidong
W
Ning
Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Wei
W
Liu
Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Feng
F
Han
Department of Neurosurgery, Xinjiang Corps Hospital, Urumqi, China.
Yijie
Y
Ma
Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Rencong
R
Wang
Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Zhou
Z
Fei
Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an, China. Electronic address: kelyue@msn.com.
Hua
H
Han
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D047494:PPAR delta / Q000819:agonists*; D048068:PPAR-beta / Q000819:agonists*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D010636:Phenols; D013438:Sulfhydryl Compounds
D053583:Interleukin-1beta; D016328:NF-kappa B; D047494:PPAR delta; D048068:PPAR-beta; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; C479979:(4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid; D010636:Phenols; D013438:Sulfhydryl Compounds
GW0742; PPAR-β/δ; anti-inflammatory; middle cerebral artery occlusion (MCAO); rat