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Oxidative stress is a crucial factor leading to subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). Isoliquiritigenin has been verified as a powerful anti-oxidant in a variety of diseases models and can activate sirtuin 1 and nuclear factor-erythroid 2-related factor 2 (Nrf2) pathways. However, the effects of isoliquiritigenin against EBI after SAH and the underlying mechanisms remain elusive.The primary goal of this study is to verify the therapeutic effects of isoliquiritigenin on EBI after SAH and the possible molecular mechanisms.A prechiasmatic cistern SAH model in rats and a hemoglobin incubation SAH model in primary neurons were established. Isoliquiritigenin was administered after SAH induction. EX527 was employed to inhibit sirtuin 1 activation and ML385 was used to suppress Nrf2 signaling.In our study, neurological scores, brain edema, biochemical estimation, western blotting, and histopathological study were performed to explore the therapeutic action of isoliquiritigenin against SAH.Our data revealed that isoliquiritigenin significantly mitigated oxidative damage after SAH as evidenced by decreased reactive oxygen species overproduction and enhanced intrinsic anti-oxidative system. Concomitant with the reduced oxidative insults, isoliquiritigenin improved neurological function and reduced neuronal death in the early period after SAH. Additionally, isoliquiritigenin administration significantly enhanced Nrf2 and sirtuin 1 expressions. Inhibition of Nrf2 by ML385 reversed the anti-oxidative and neuroprotective effects of isoliquiritigenin against SAH. Moreover, inhibiting sirtuin 1 by EX527 pretreatment suppressed isoliquiritigenin-induced Nrf2-dependent pathway and abated the cerebroprotective effects of isoliquiritigenin. In primary cortical neurons, isoliquiritigenin treatment also ameliorated oxidative insults and repressed neuronal degeneration. The beneficial aspects of isoliquiritigenin were attributed to the promotion of sirtuin 1 and Nrf2 signaling pathways and were counteracted by EX527.Our findings suggest that isoliquiritigenin exerts cerebroprotective effects against SAH-induced oxidative insults by modulating the Nrf2-mediated anti-oxidant signaling in part through sirtuin 1 activation. Isoliquiritigenin might be a new potential drug candidate for SAH.

Objective: Intraventricular hemorrhage (IVH) is characterized by acute onset, rapid progression, and high disability and mortality rates. In this study, we investigated the clinical effect of external ventricular drainage combined with continuous lumbar drainage in IVH treatments. Methods: 114 patients with IVH treated at the Department of Neurosurgery, First Affiliated Hospital of Wannan Medical College from January 2015 to December 2017, were included in the study. Based on the different surgical methods, patients were divided into control (n=79) and study groups (n=35). The control group was treated with external ventricular drainage, whereas the study group was treated with external ventricular drainage combined with continuous lumbar drainage. The incidence of intracranial infection and hydrocephalus was compared between the two groups. The Glasgow coma scale (GCS) and the Glasgow outcome scale (GOS) were compared between the two groups 7 days postoperatively and at follow-up visits, respectively. Results: The incidence of intracranial infection and hydrocephalus in the study group was significantly lower compared with those in the control group (P

Background: This study was aimed to investigate the molecular mechanism of how melatonin interferes with hypoxia-inducible factor 1α (HIF1A) and TLR4 expression, which is implicated in the management of delayed brain injury (DBI) after subarachnoid hemorrhage (SAH). Method: Luciferase assay, real-time PCR, Western-blot analysis and immunohistochemistry (IHC) assays were utilized to explore the interaction among H19, miR-675, HIF1A and TLR4, and to evaluate the effect of MT on the expression of above transcripts in different groups. Results: MT enhanced H19 expression by promoting the transcription efficiency of H19 promoter, and HIF1A was identified as a target of miR-675. HIF1A enhanced TLR4 expression via promoting the transcription efficiency of TLR4 promoter. Furthermore, administration of MT up-regulated miR-675 but suppressed the expressions of HIF1A and TLR4. Treatment with MT alleviated neurobehavioral deficits and apoptosis induced by SAH. According to the result of IHC, HIF1A and TLR4 protein levels in the SAH group were much higher than those in the SAH+MT group. Therefore, the administration of MT increased the levels of H19 and miR-675 which have been inhibited by SAH. In a similar way, treatment with MT decreased the levels of HIF1A and TLR4 which have been enhanced by SAH. Conclusion: MT could down-regulate the expression of HIF1A and TLR4 via the H19/miR-675/HIF1A/TLR4 signaling pathway, while TLR4 is crucial to the release of pro-inflammatory cytokines. Therefore, the treatment with MT could ameliorate post-SAH DBI.

miRNAs are important regulators of translation and have been associated with the pathogenesis of a number of cardiovascular diseases including stroke and may be possible prognostic biomarkers. The purpose of the present study was to determine the expression levels of miRNAs in the sera of subarachnoid haemorrhage (SAH) patients and to evaluate their relationships with the severity and clinical outcome of SAH. Serum samples on day 3 after the onset of SAH were subjected to microarray analysis with Exqion miRCURYTM LNA array and quantitative PCR analysis. Serum samples from SAH patients (n=60) and healthy controls (n=10) were subjected to quantitative PCR analysis. The severities and clinical outcomes of the SAH patients were evaluated with the WFNS grade and the Modified Rankin Scale (mRS). Three miRNAs, miR-502-5p, miR-1297 and miR-4320 were significantly up-regulated in the sera of SAH patients when compared with the healthy controls. The serum miR-502-5p and miR-1297 levels were significantly higher in the patients with severe SAH and a poor outcome than in those with mild SAH and a good outcome (P

In order to investigate the size effect and other effects on the stress-strain relationship of confined concrete, 42 specimens with different sizes and section shapes were placed under axial compression loading. Effects of key parameters such as size of specimens, tie configuration, transverse reinforcement ratio, and concrete cover were studied. The results show that for specimens with the same configuration and the same volumetric ratio of the transverse reinforcement, along with the increasing specimen size, the peak stress, peak strain and deformation of the post-peak show a down trend, however, the volumetric ratio of the transverse reinforcement is lowered, the decreasing of the peak stress is accelerated, but the decreasing of the deformation is slow down. For specimens with the same volumetric ratio but different configurations of transverse reinforcement, though the transverse reinforcement configuration becomes more complicated, the peak stress of the large size specimen does not improve more than that of the small size. However, the deformation occurs before the stress declines to 85% of peak stress, and the improvement with the grid pattern tie configuration is much greater due to size effect.