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.

内源性消除血肿是解决脑出血 (ICH) 的有利策略。本研究旨在确定类视黄醇 X 受体-α (RXR-α) 在 ICH 后血肿吸收中的作用。我们的研究结果表明，用贝沙罗汀药理学激活 RXR-α 可显着加速血肿清除并减轻 ICH 后的神经功能障碍。RXR-α 在小胶质细胞/巨噬细胞、神经元和星形胶质细胞中表达。从机制上讲，贝沙罗汀促进了 RXR-α 和 PPAR-γ 的核转位，并通过调节小胶质细胞/巨噬细胞从 M1 重编程为 M2 表型来减少神经炎症。此外，RXR-α 在 ICH 中的所有有益作用都被 PPAR-γ 抑制剂 GW9662 逆转。综上所述，RXR-α 的药理学激活通过 PPAR-γ 相关机制加速血肿清除和将小胶质细胞/巨噬细胞重新极化为 M2 表型，从而对 ICH 提供强大的神经保护作用。我们的数据支持 RXR-α 可能是 ICH 的一个有希望的治疗靶点的观点。