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.
Subject(s)
Humans , Anilides/pharmacology , Cerebral Hemorrhage/drug therapy , Hematoma/drug therapy , Macrophages , Microglia , Neuroprotection , PPAR gamma , Retinoid X Receptor alphaABSTRACT
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.
ABSTRACT
BACKGROUND:Peripheral facial nerve injury first involves the retrograde reactions of central nervous system axons, and nerve regeneration wil depend on the survival and functional status of neuronal cel bodies. OBJECTIVE:To explore the expression of neuronal cadherin and placental cadherin in facial nuclei after facial nerve injury. METHODS:New Zealand white rabbits were randomly divided into model group (n=48) and control group (n=8). In the model group, every eight rabbits were used to carry out the test respectively at 1, 4, 7, 14, 21 days after the model of facial nerve injury (right side) was established. SP and real-time quantitative PCR methods were taken to test the expression of neuronal cadherin and placental cadherin in the facial nerve nucleus at mRNA and RESULTS AND CONCLUSION:The control group had neuronal cadherin-and placental cadherin-positive neurons. In the model group, neuronal cadherin and placental cadherin positively expressed in the facial motorneurons (right side), and their expressions were peaked at 14 days. Compared with the control group, the mRNA expression of neuronal cadherin in the facial motorneurons was increased significantly at 4-28 days after injury;the mRNA expression of placental cadherin in the facial motorneurons was decreased significantly at 1 day after injury, and then increased significantly at 7-28 days. It is suggested that the expression of neuronal cadherin and placental cadherin is positive in the early stage of facial nerve injury, and the expression of placental cadherin is always present, while the expression of neuronal cadherin relatively lasts for a short time. After facial nerve injury, the expression of neuronal cadherin and placental cadherin in the facial nerve nucleus is both increased, which indicates that the facial nerve regeneration may be related to the high expression of adhesion molecules.