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
The clinical and urodynamic data of 37 patients with benign prostate hyperplasia (BPH) and 30 diabetic patients complicated with BPH (BPH+DM) admitted between Jan 2014 and July 2017 were analyzed retrospectively. The International Prostate Symptom Score (IPSS), maximal flow rate (Qmax), post-voiding residual urine volume (PVR), maximum cystometric capacity (MCC), first desire to void (FDV), pressure of detrusor maximum (Pdet, max), bladder outlet obstruction index (BOOI), bladder contraction index (BCI) were compared between BPH group and BPH+DM group. According to BOOI-BCI linear regression, 22 cases (group A) and 15 cases (group B) of BPH patients were above and below the linear curve; while there were 14 cases (group C) and 16 cases(group D)of BPH+DM patients above and below the curve, respectively. The mean±SD FDV, MCC, Pdet, max, PVR, BOOI, BCI were (172.7±93.0)ml vs. (300.5±118.4)ml (P<0.05), (311.9±147.1)ml vs. (509.3±98.6)ml (P<0.05), (84.7±51.5)cmH2O(1 cm H2O=0.098 kPa) vs. (49.7± 32.9)cmH2O vs (P<0.05), 10.0 ml(0—200 ml) vs. 41.5 ml(0—450 ml), 69.7 ± 53.7 vs. 35.9 ± 32.3 (P<0.05), 122.3±50.2 vs 84.2±43.3 (P<0.05) in BPH and BPH+DM groups, respectively. In BPH group and BPH+DM group, the regression coefficients of BOOI-BCI were 0.889 and 0.724, respectively. In group A and group B, the difference value of IPSS and Qmax pre and post operation were 7.6±3.5 and 7.3±4.1 (P>0.05), (2.6±1.1)ml/s and (3.7±1.3) ml/s (P<0.05), respectively. In group C and group D, the difference value of IPSS and Qmax pre and post operation were 5.3 ± 2.4 and 6.0 ± 3.3 (P>0.05), (2.4 ± 1.0)ml/s and (3.8 ± 1.4)ml/s (P<0.05), respectively. The study indicates that the therapeutic effect is better for the patients blow BOOI-BCI regression linear curve compared to the patients above the linear curve.