Activation of retinoid X receptor by bexarotene attenuates neuroinflammation via PPARγ/SIRT6/FoxO3a pathway after subarachnoid hemorrhage in rats

Journal of Neuroinflammation
Yuchun ZuoJohn H Zhang

Abstract

Subarachnoid hemorrhage (SAH) is a life-threatening subtype of stroke with high mortality and disabilities. Retinoid X receptor (RXR) has been shown to be neuroprotective against ischemia/reperfusion injury. This study aimed to investigate the effects of the selective RXR agonist bexarotene on neuroinflammation in a rat model of SAH. Two hundred male Sprague-Dawley rats were used. The endovascular perforation induced SAH. Bexarotene was administered intraperitoneally at 1 h after SAH induction. To investigate the underlying mechanism, the selective RXR antagonist UVI3003 and RXR siRNA or SIRT6 inhibitor OSS128167 was administered via intracerebroventricular 1 h before SAH induction. Post-SAH assessments including SAH grade, neurological score, brain water content, Western blot, and immunofluorescence were performed. The endogenous RXR and sirtuin 6 (SIRT6) protein levels were increased after SAH. Bexarotene treatment significantly reduced brain edema and improved the short-/long-term neurological deficit after SAH. Mechanistically, bexarotene increased the levels of PPARγ and SIRT6; decreased the expression of phosphorylated FoxO3a (p-FoxO3a), IL-6, IL-1β, and TNF-a; and inhibited the microglia activation and neutrophils infilt...Continue Reading

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Citations

May 20, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Rafal MorgaJoanna Pera
Dec 17, 2020·Medicinal Research Reviews·Gang LiuJia Zhou
Nov 14, 2020·Acta Neuropathologica Communications·Angie C A ChiangCobi J Heijnen
Jun 15, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ya-Qun ZhouDa-Wei Ye
May 1, 2021·International Journal of Molecular Sciences·Matthias Simon, Alexander Grote
May 18, 2021·Frontiers in Pharmacology·Ruizhen HuangHonglin Hu
Jun 3, 2021·International Journal of Molecular Sciences·Judith WeilandNadine Lilla

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Methods Mentioned

BETA
Immunoprecipitation

Software Mentioned

Graph Pad
MassHunter
ImageJ J
SigmaPlot
SPSS
Graph Pad Prism

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