Background: 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.Methods: ICH mouse models were established by the stereotactic injection of autologous arterial blood into the right basal ganglia. The selective RXR-α agonist bexarotene and peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist GW9662 were administered intraperitoneally at 1 h after ICH. Post-ICH assessments were in the form of magnetic resonance imaging scans, neurological tests, Western blotting, enzyme-linked immunosorbent assays, and immunofluorescence. Results: Pharmacologically activating RXR-α with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH. RXR-α was expressed in the microglia/macrophages, neurons, and astrocytes. Mechanically, bexarotene promoted the nuclear translocation of RXR-α and PPAR-γ, alongside reducing neuroinflammation by modulating microglia/macrophages reprograming into the M2 phenotype from M1 phenotype. However, all the beneficial effects of RXR-α in ICH were reversed by the PPAR-γ inhibitor GW9662.Conclusion: The pharmacological activation of RXR-α conferred 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.

BackgroundIt’s well known that long noncoding RNAs (lncRNAs) contribute to multiple biological processes of human glioblastoma (GBM). However, identifying a specific lncRNA target is still the major difficulty. In this study, bioinformatics methods and competing endogenous RNA network (ceRNA) regulatory rules was used to identify GBM related lncRNAs, and found OXCT1 antisense RNA 1 (OXCT1-AS1) may acted as a potential therapeutic target for treatment of glioma.MethodsBased on the Gene Expression Omnibus (GEO) date set, we identified differential lncRNAs, microRNAs and mRNAs and constructed a lncRNA associated ceRNA network.Novel lncRNA OXCT1-AS1 was proposed to exercise its function as a ceRNA, and its potential targeted miRNAs was predicted through the database LncBase Predicted v.2. The expression pattern of OXCT1-AS1 was measured in glioma and normal tissue samples. Effect of OXCT1-AS1 on glioma cells were checked by cell count kit 8 assay, cell clone formation assay, transwell assay and flow cytometry in vitro, respectively. The dual-luciferase activity assay was performed to investigate the potential mechanism of ceRNA network. Finally, orthotopic mouse models of glioma was created to evaluate the influence of OXCT1-AS1 on tumor growth in vivo.ResultsIn this study, it was found that the expression of lncRNA OXCT1-AS1 is upregulated in both The Cancer Genome Atlas (TCGA) GBM cases and GBM tissue samples we collected, and a high expression of OXCT1-AS1 predicts poor prognosis of gliomas. Suppressing OXCT1-AS1 expression significantly decreased the proliferation of GBM cells and inhibited cell migration and invasion. We further investigated the potential mechanism and found OXCT1-AS1 may acted as a ceRNA of miR-195 to enhance CDC25A expression and attenuate glioma cells progression. Finally, knocking down of OXCT1-AS1 notably attenuated the severity of glioma in vivo.ConclusionOXCT1-AS1 inhibited glioma progression by regulating miR-195-5p/ CDC25A axis and can be a specific tumor marker and a novel potential therapeutic target for glioma treatment.