Astrocyte-mediated neuroinflammation plays a critical role in ischemic stroke-induced secondary cerebral injury. Previous studies have suggested that the dopamine D2 receptor (DRD2) acts as a key target in regulating the neuroinflammatory response. However, the underlying molecular mechanisms are still unknown, and effective DRD2 agonists are lacking. In the present study, we examined the anti-inflammatory and neuroprotective effects of sinomenine (Sino), a monomeric compound with potential immunoregulatory properties in nervous system. TTC staining, apoptosis assay, evaluation of brain edema, and neurological assessment were performed in the middle cerebral artery occlusion (MCAO) mouse model. Primary astrocytes exposed to oxygen glucose deprivation (OGD) were used in the in vitro experiments. Quantitative PCR was applied to assess the levels of inflammatory cytokines. Multi-labeling immunofluorescence, Western blot, co-immunoprecipitation, and electrophoretic mobility shift assay (EMSA) were also used to investigate the molecular mechanisms underlying the Sino-mediated anti-inflammatory effects in vivo and in vitro. Sino remarkably attenuated the cerebral infarction and neuronal apoptosis, reduced the levels of inflammatory cytokines, and alleviated neurological deficiency in MCAO mice. Sino significantly inhibited astrocytic activation and STAT3 phosphorylation as well as increased DRD2 and αB-crystallin (CRYAB) expression after MCAO. In vitro, Sino blocked OGD-induced activation of STAT3 and generation of pro-inflammatory cytokines in primary astrocytes, and these effects were significantly abolished by either DRD2 or CRYAB knockdown. Additionally, Sino induced up-regulation and nuclear translocation of CRYAB in astrocytes and enhanced the interaction between CRYAB and STAT3, which further inhibited the activation and DNA-binding activity of STAT3. Our study demonstrates that Sino activates astrocytic DRD2 and thereby suppresses neuroinflammation via the CRYAB/STAT3 pathway, which sheds some light on a promising therapeutic strategy for ischemic stroke.

Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke, which leads to a high rate of mortality and poor neurological outcomes worldwide. Thrombolytic evacuation with urokinase-type plasminogen activator (uPA) or tissue-type plasminogen activator (tPA) has been showed to be a hopeful treatment for ICH. However, to the best of our knowledge, no clinical trials were reported to compare the efficacy and safety of these two fibrinolytics administrated following minimally invasive stereotactic puncture (MISP) in patients with spontaneous basal ganglia ICH. Therefore, the authors intended here to evaluate the differential impact of uPA and tPA in a retrospective study. In the present study, a total of 86 patients with spontaneous ICH in basal ganglia using MISP received either uPA (uPA group, n=45) or tPA (tPA group, n=41), respectively. The clinical baseline characteristics prior to the operation were collected. In addition, therapeutic responses were assessed by the short-term outcomes within 30 days postoperation, as well as long-term outcomes at 1 year postoperation. Our findings showed that, in comparison with tPA, uPA was able to better promote hematoma evacuation and ameliorate perihematomal edema, but the differences were not statistically significant. Moreover, the long-term functional outcomes of both groups were similar, with no statistical difference. In conclusion, these results provide evidence supporting that uPA and tPA are similar in the efficacy and safety for thrombolytic evacuation in combination with MISP in patients with spontaneous basal ganglia ICH.

Long noncoding RNA AB073614 promotes the malignance of glioma by activating Wnt/-catenin signaling through downregulating SOX7 Long noncoding RNA AB073614 promotes the malignance of glioma by activating Wnt/β-catenin signaling through downregulating SOX7