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Background and Purpose Inflammatory injury plays a critical role in intracerebral hemorrhage (ICH)-induced secondary brain injury. Recently, Dopamine D2 receptor (DRD2) is identified an important component controlling innate immunity and inflammatory response in central nervous system and αB-crystallin (CRYAB) is a potent negative regulator on inflammatory pathways. Here, we sought to investigate the role of DRD2 on neuroinflammation after experimental ICH, and the potential mechanism mediated by CRYAB. Methods Two hundred and twenty-four (224) male CD-1 mice were subjected to intrastriatal infusion of bacterial collagenase or autologous blood. Two DRD2 agonists Quinpirole and Ropinirole were administrated by daily intraperitoneal injection starting at 1 hour post-ICH. DRD2 and CRYAB in vivo knockdown was performed 48 hour before ICH insult. Behavioral deficits and brain water content, western blots, immunofluorescence staining, co-immunoprecipitation assay and proteome cytokine array were evaluated. Results Endogenous DRD2 and CRYAB expression were increased after ICH. DRD2 knockdown aggravated the neurobehavioral deficits and the pronounced cytokines expression. DRD2 activation by Quinpirole and Ropinirole ameliorated neurological outcome, brain edema, IL-1β and MCP-1 expression, as well as microglia/macrophages activation in the perihematomal region. These effects were abolished by pretreated with CRYAB siRNAs. Quinpirole enhanced cytoplasmic binding activity between CRYAB and NF-κB, and decreased nuclear NF-κB expression. Similar therapeutic benefits were observed using autologous blood injection model and intranasal delivery of Quinpirole. Conclusions DRD2 may have anti-inflammatory effects after ICH. DRD2 agonists inhibited neuroinflammation and attenuated brain injury after ICH, which is probably mediated by CRYAB and enhanced cytoplasmic binding activity with NF-κB.

Traditional anti-diabetic drugs may have negative or positive effects on risk of bone fractures. Yet the relationship between the new class glucagon-like peptide-1 receptor agonists (GLP-1 RA) and risk of bone fractures has not been established. We performed a meta-analysis including randomized controlled trials (RCT) to study the risk of bone fractures associated with liraglutide or exenatide, compared to placebo or other active drugs. We searched MEDLINE, EMBASE, and clinical trial registration websites for published or unpublished RCTs comparing the effects of liraglutide or exenatide with comparators. Only studies with disclosed bone fracture data were included. Separate pooled analysis was performed for liraglutide or exenatide, respectively, by calculating Mantel-Haenszel odds ratio (MH-OR). 16 RCTs were identified including a total of 11,206 patients. Liraglutide treatment was associated with a significant reduced risk of incident bone fractures (MH-OR=0.38, 95% CI 0.17-0.87); however, exenatide treatment was associated with an elevated risk of incident bone fractures (MH-OR=2.09, 95% CI 1.03-4.21). Publication bias and heterogeneity between studies were not observed. Our study demonstrated a divergent risk of bone fractures associated with different GLP-1 RA treatments. The current findings need to be confirmed by future well-designed prospective or RCT studies.