Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage(ICH).This study sought to determine the role of retinoid X receptor-ot(RXR-a)in the context of hematoma absorption a...Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage(ICH).This study sought to determine the role of retinoid X receptor-ot(RXR-a)in the context of hematoma absorption after ICH.Our results showed that pharmacologically activating RXR-a with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH.RXR-ot was expressed in microglia/macro-phages,neurons,and astrocytes.Mechanistically,bexarotene promoted the nuclear translocation of RXR-a and PPAR-y,as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the Ml into the M2 phenotype.Furthermore,all the beneficial effects of RXR-a in ICH were reversed by the PPAR-y inhibitor GW9662.In conclusion,the pharmacological activation of RXR-a confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-y-related mechanisms.Our data support the notion that RXR-ot might be a promising therapeutic target for ICH.展开更多
基金by the National Key R&D Program of China(2018YFC1312600 and 2018YFC1312603)the Key Research and Development Project of Zhejiang Province(2018C03011)+1 种基金the National Natural Science Foundation of China(81771246,81971099,and 81870908)the Scientific Research Fund of Zhejiang Provincial Education Department(Y201941838).
文摘Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage(ICH).This study sought to determine the role of retinoid X receptor-ot(RXR-a)in the context of hematoma absorption after ICH.Our results showed that pharmacologically activating RXR-a with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH.RXR-ot was expressed in microglia/macro-phages,neurons,and astrocytes.Mechanistically,bexarotene promoted the nuclear translocation of RXR-a and PPAR-y,as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the Ml into the M2 phenotype.Furthermore,all the beneficial effects of RXR-a in ICH were reversed by the PPAR-y inhibitor GW9662.In conclusion,the pharmacological activation of RXR-a confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-y-related mechanisms.Our data support the notion that RXR-ot might be a promising therapeutic target for ICH.
