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.
Anilides/pharmacology* ; Cerebral Hemorrhage/drug therapy* ; Hematoma/drug therapy* ; Humans ; Macrophages ; Microglia ; Neuroprotection ; PPAR gamma ; Retinoid X Receptor alpha

OBJECTIVETo apply linkage disequilibrium (LD) maps to associations studies with high throughput single nucleotide polymorphisms (SNPs).

METHODSSeven hundred and fifty-four SNPs were genotyped in 160 Shanghai Chinese. LD maps were constructed in cases and controls separately. By comparing the decline of LD unit with distance between the two groups, disease susceptible loci were estimated. This method was compared with traditional analyses including LD analysis, single SNP and haplotype analyses.

RESULTSThe analysis of LD maps could detect the chromosome regions with different LD patterns between the cases and controls. The alleles and/or haplotypes frequencies of SNPs within the regions had significantly different distributions or trends of significantly different distributions.

CONCLUSIONThis method may be applied to analyze the data from association studies with high throughput SNPs genotype information.

Adult ; Aged ; Case-Control Studies ; DNA-Binding Proteins ; genetics ; Diabetes Mellitus, Type 2 ; genetics ; Female ; Gene Frequency ; Genome-Wide Association Study ; methods ; Haplotypes ; Humans ; Linkage Disequilibrium ; Male ; Polymorphism, Single Nucleotide ; Pre-B-Cell Leukemia Transcription Factor 1 ; Proto-Oncogene Proteins ; genetics ; Retinoid X Receptor gamma ; genetics