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.
Key Words
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References
- NXY-059 for acute ischemic stroke.N Engl J Med. 2006; 354: 588-600
- Demographic, clinical, and radiologic predictors of neurologic deterioration in patients with acute ischemic stroke.J Stroke Cerebrovasc Dis. 2013; 22: 205-210
- Neuroprotective effects of leonurine on ischemia/reperfusion-induced mitochondrial dysfunctions in rat cerebral cortex.Biol Pharm Bull. 2010; 33: 1958-1964
- Peroxisome-proliferator-activated receptors and cancers: complex stories.Nat Rev Cancer. 2004; 4: 61-70
- GW0742, a high-affinity PPAR-beta/delta agonist, inhibits acute lung injury in mice.Shock. 2010; 33: 426-435
- Activation of cerebral peroxisome proliferator-activated receptors gamma promotes neuroprotection by attenuation of neuronal cyclooxygenase-2 overexpression after focal cerebral ischemia in rats.FASEB J. 2006; 20: 1162-1175
- Oxidative stress and inflammatory response evoked by transient cerebral ischemia/reperfusion: effects of the PPAR-alpha agonist WY14643.Free Radic Biol Med. 2006; 41: 579-589
- Peroxisome proliferator-activated receptor beta/delta exerts a strong protection from ischemic acute renal failure.J Am Soc Nephrol. 2005; 16: 2395-2402
- GW0742, a selective PPAR-beta/delta agonist, contributes to the resolution of inflammation after gut ischemia/reperfusion injury.J Leukoc Biol. 2010; 88: 291-301
- Modulation of LPS-induced pulmonary neutrophil infiltration and cytokine production by the selective PPARbeta/delta ligand GW0742.Inflamm Res. 2008; 57: 314-321
- The PPAR-delta agonist GW0742 reduces atherosclerosis in LDLR (2/2) mice.Atherosclerosis. 2005; 181: 29-37
- Activation of peroxisome proliferator-activated receptor-beta/delta attenuates myocardial ischemia/reperfusion injury in the rat.Shock. 2010; 34: 117-124
- Activation of peroxisome proliferator-activated receptor beta/delta inhibits lipopolysaccharide-induced cytokine production in adipocytes by lowering nuclear factor-kappaB activity via extracellular signal-related kinase 1/2.Diabetes. 2008; 57: 2149-2157
- Increased infarct size and lack of hyperphagic response after focal cerebral ischemia in peroxisome proliferator-activated receptor beta-deficient mice.J Cereb Blood Flow Metab. 2006; 26: 433-445
- Modification of the method of thread manufacture improves stroke induction rate and reduces mortality after thread-occlusion of the middle cerebral artery in young or aged rats.J Neurosci Methods. 2006; 155: 285-290
- Reversible middle cerebral artery occlusion without craniectomy in rats.Stroke. 1989; 20: 84-91
- Ischemic brain edema and the osmotic gradient between blood and brain.J Cereb Blood Flow Metab. 1988; 8: 552-559
- Peroxisome proliferator-activated receptors ligands and ischemia-reperfusion injury.Naunyn Schmiedebergs Arch Pharmacol. 2007; 375: 157-175
- Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor alpha in mice.Neurosci Lett. 2003; 352: 203-206
- Protective role of peroxisome proliferator-activated receptor-β/δ in septic shock.Am J Respir Crit Care Med. 2010; 182: 1506-1515
- PPAR-δ modulates lipopolysaccharide-induced TNF-α inflammation signaling in cultured cardiomyocytes.J Mol Cell Cardiol. 2006; 40: 821-828
- Nuclear factor (NF)-kappaB proteins: therapeutic targets.Ann Rheum Dis. 2004; 63: 57-61
- Protective effects of Guizhi-Fuling-Capsules on rat brain ischemia/reperfusion injury.J Pharmacol Sci. 2007; 105: 34-40
- Tumour necrosis factor receptor gene therapy affects cellular immune responses in collagen induced arthritis in mice.Ann Rheum Dis. 2005; 64: 1550-1556
- Ligand activation of peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) attenuates carbon tetrachloride hepatotoxicity by downregulating proinflammatory gene expression.Toxicol Sci. 2008; 105: 418-428
- Treatment with Z-ligustilide, a component of Angelica sinensis, reduces brain injury after a subarachnoid hemorrhage in rats.J Pharmacol Exp Ther. 2011; 337: 663-672
- Neuroprotective efficacy of the peroxisome proliferator-activated receptor delta-selective agonists in vitro and in vivo.J Pharmacol Exp Ther. 2007; 320: 1087-1096
- Evidence for the role of peroxisome proliferator-activated receptor-beta/delta in the development of spinal cord injury.J Pharmacol Exp Ther. 2010; 33: 465-477
Article info
Publication history
Published online: April 28, 2014
Accepted:
November 23,
2013
Received in revised form:
November 7,
2013
Received:
September 22,
2013
Footnotes
X.C., C.X., and W.D. contributed equally to this work.
This work was financially supported by the National Natural Science Foundation of China (81301075) and China Postdoctoral Science Foundation (2012M512099).
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.11.021
Copyright
© 2014 Published by Elsevier Inc. All rights reserved.
