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

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

  • Neurosci Bull. 2021 Oct;37(10):1412-1426. doi: 10.1007/s12264-021-00735-3.
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
Affiliations

Affiliations

  • 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.
  • # Contributed equally.
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.

Keywords

Intracerebral hemorrhage; Neuroinflammation; PPAR-γ; Phagocytosis; Polarization; RXR-α.

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