Open AccessPharmacological Activation of RXR-α Promotes Hematoma Absorption via a PPAR-γ-dependent Pathway After Intracerebral Hemorrhage
Author(s) -
Chaoran Xu,
Huaijun Chen,
Zhou Shengjun,
Chenjun Sun,
Xiaolong Xia,
Yucong Peng,
Jianfeng Zhuang,
Xiongjie Fu,
Hanhai Zeng,
Hang Zhou,
Yang Cao,
Qian Yu,
Li Yin,
Libin Hu,
Guoyang Zhou,
Feng Yan,
Gao Chen,
Jianru Li
Publication year - 2021
Publication title -
neuroscience bulletin/neuroscience bulletin
Language(s) - English
Resource type - Journals
eISSN - 1673-7067
pISSN - 1995-8218
DOI - 10.1007/s12264-021-00735-3
Subject(s) - retinoid x receptor , bexarotene , microglia , neuroprotection , neuroinflammation , pharmacology , medicine , peroxisome proliferator activated receptor , intracerebral hemorrhage , hematoma , context (archaeology) , neuroscience , chemistry , receptor , nuclear receptor , biology , transcription factor , biochemistry , inflammation , surgery , subarachnoid hemorrhage , gene , paleontology
Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage (ICH). This study sought to determine the role of retinoid X receptor-α (RXR-α) in the context of hematoma absorption after ICH. Our results showed that pharmacologically activating RXR-α with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH. RXR-α was expressed in microglia/macrophages, neurons, and astrocytes. Mechanistically, bexarotene promoted the nuclear translocation of RXR-α and PPAR-γ, as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the M1 into the M2 phenotype. Furthermore, all the beneficial effects of RXR-α in ICH were reversed by the PPAR-γ inhibitor GW9662. In conclusion, the pharmacological activation of RXR-α confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-γ-related mechanisms. Our data support the notion that RXR-α might be a promising therapeutic target for ICH.