Activation of peroxisome proliferator-activated receptor β/δ attenuates acute ischemic stroke on middle cerebral ischemia occlusion in rats.

Abstract

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.

• Authors: Xiaodong Chao, Chunlei Xiong, Weifeng Dong, Yan Qu, Weidong Ning, Wei Liu, Feng Han, Yijie Ma, Rencong Wang, Zhou Fei, Hua Han
• Journal: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association (J Stroke Cerebrovasc Dis) Vol. 23 Issue 6 Pg. 1396-402 (Jul 2014) ISSN: 1532-8511 [Electronic] United States
• PMID: 24774438 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Chemical References

• Interleukin-1beta
• NF-kappa B
• PPAR delta
• PPAR-beta
• Thiazoles
• Tumor Necrosis Factor-alpha
• (4-(((2-(3-fluoro-4-(trifluoromethyl)phenyl)-4-methyl-1,3-thiazol-5-yl)methyl)sulfanyl)-2-methylphenoxy)acetic acid

Topics

• Animals
• Brain (drug effects, pathology, physiopathology)
• Brain Ischemia (drug therapy, pathology, physiopathology)
• Infarction, Middle Cerebral Artery (drug therapy, pathology, physiopathology)
• Interleukin-1beta (metabolism)
• Male
• Motor Activity (drug effects, physiology)
• NF-kappa B (metabolism)
• PPAR delta (agonists)
• PPAR-beta (agonists)
• Rats
• Rats, Sprague-Dawley
• Stroke (drug therapy, physiopathology)
• Thiazoles (pharmacology, therapeutic use)
• Tumor Necrosis Factor-alpha (metabolism)