Pharmacological Activation of RXR-α Promotes Hematoma Absorption via a PPAR-γ-dependent Pathway After Intracerebral Hemorrhage
- Author:
Chaoran XU
1
;
Huaijun CHEN
1
;
Shengjun ZHOU
1
;
Chenjun SUN
1
;
Xiaolong XIA
1
;
Yucong PENG
1
;
Jianfeng ZHUANG
1
;
Xiongjie FU
1
;
Hanhai ZENG
1
;
Hang ZHOU
1
;
Yang CAO
1
;
Qian YU
1
;
Yin LI
1
;
Libin HU
1
;
Guoyang ZHOU
1
;
Feng YAN
1
;
Gao CHEN
1
;
Jianru LI
1
Author Information
- Publication Type:Journal Article
- Keywords: Intracerebral hemorrhage; Neuroinflammation; Phagocytosis; Polarization; PPAR-γ; RXR-α
- From: Neuroscience Bulletin 2021;37(10):1412-1426
- CountryChina
- Language:Chinese
- Abstract: 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.
