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

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

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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 ² ; Jianru LI ³
Author Information

1. Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310052, China.
2. Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310052, China. d-chengao@zju.edu.cn.
3. Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, 310052, China. lijianru@zju.edu.cn.
Publication Type:Journal Article
Keywords: Intracerebral hemorrhage; Neuroinflammation; PPAR-γ; Phagocytosis; Polarization; RXR-α
MeSH: Anilides/pharmacology*; Cerebral Hemorrhage/drug therapy*; Hematoma/drug therapy*; Humans; Macrophages; Microglia; Neuroprotection; PPAR gamma; Retinoid X Receptor alpha
From: Neuroscience Bulletin 2021;37(10):1412-1426
CountryChina
Language:English
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.