Pharmacological Activation of RXR-a Promotes Hematoma Absorption via a PPAR-y-dependent Pathway After Intracerebral Hemorrhage  

作　　者：Chaoran Xu Huaijun Chen Shengjun Zhou Chenjun Sun Xiaolong Xia Yucong Peng Jianfeng Zhuang Xiongjie Fu Hanhai Zeng Hang Zhou Yang Cao Qian Yu Yin Li Libin Hu Guoyang Zhou Feng Yan Gao Chen Jianru Li 

机构地区：[1]Department of Neurosurgery,The Second Affiliated Hospital of Zhejiang University School of Medicine,Hangzhou 310052,China

出　　处：《Neuroscience Bulletin》2021年第10期1412-1426,共15页神经科学通报（英文版）

基　　金：by the National Key R&D Program of China(2018YFC1312600 and 2018YFC1312603);the Key Research and Development Project of Zhejiang Province(2018C03011);the National Natural Science Foundation of China(81771246,81971099,and 81870908);the Scientific Research Fund of Zhejiang Provincial Education Department(Y201941838).

摘　　要：Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage(ICH).This study sought to determine the role of retinoid X receptor-ot(RXR-a)in the context of hematoma absorption after ICH.Our results showed that pharmacologically activating RXR-a with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH.RXR-ot was expressed in microglia/macro-phages,neurons,and astrocytes.Mechanistically,bexarotene promoted the nuclear translocation of RXR-a and PPAR-y,as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the Ml into the M2 phenotype.Furthermore,all the beneficial effects of RXR-a in ICH were reversed by the PPAR-y inhibitor GW9662.In conclusion,the pharmacological activation of RXR-a confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-y-related mechanisms.Our data support the notion that RXR-ot might be a promising therapeutic target for ICH.

关 键 词：Intracerebral hemorrhage RXR-a PPAR-y Polarization PHAGOCYTOSIS NEUROINFLAMMATION 

分 类 号：R743.34[医药卫生—神经病学与精神病学]