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(1) Background: Sleep deprivation (SD) triggers a range of neuroinflammatory responses. Dexmedetomidine can improve sleep deprivation-induced anxiety by reducing neuroinflammatory response but the mechanism is unclear; (2) Methods: The sleep deprivation model was established by using an interference rod device. An open field test and an elevated plus maze test were used to detect the emotional behavior of mice. Mouse cortical tissues were subjected to RNA sequence (RNA-seq) analysis. Western blotting and immunofluorescence were used to detect the expression of p38/p-p38, MSK1/p-MSK1, and NFκBp65/p- NFκBp65. Inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA); (3) Results: SD triggered anxiety-like behaviors in mice and was closely associated with inflammatory responses and the MAPK pathway (as demonstrated by transcriptome analysis). SD led to increased expression levels of p-p38, p-MSK1, and p-NFκB. P38 inhibitor SB203580 was used to confirm the important role of the p38/MSK1/NFκB pathway in SD-induced neuroinflammation. Dexmedetomidine (Dex) effectively improves emotional behavior in sleep-deprived mice by attenuating SD-induced inflammatory responses and oxidative stress in the cerebral cortex, mainly by inhibiting the activation of the p38/MSK1/NFκB pathway; (4) Conclusions: Dex inhibits the activation of the p38/MSK1/NFκB pathway, thus attenuating SD-induced inflammatory responses and oxidative stress in the cerebral cortex of mice. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke is a major health issue that causes high incidents of morbidity and mortality worldwide. Irisin is an excise-induced protein that has exhibited pleiotropic properties. Accumulating evidence reveals its critical roles in the regulation of various cellular functions, including nervous system functions. This study aims to disclose the effect of irisin on rat cerebral neurons suffering from hypoxia/reoxygenation (H/R) treatment and to explore the potential underlying molecular mechanisms. Methods: The percentage of rat cerebral neuron cell death was determined by flow cytometry analysis and MTT assay. The expression levels of target genes were measured by western blotting and real-time quantitative reverse transcription PCR assay. Results: Our results demonstrated that irisin treatment substantially reduced H/R-induced apoptosis of rat cerebral neurons. Further investigation revealed that irisin treatment markedly decreased mitogen-activated protein kinase (MAPK) signaling pathway activation and suppressed pro-informatory cytokine expression in cerebral neurons with H/R challenge. Finally, we showed that the neuroprotective effect and anti-inflammatory effect of irisin were comparable with three MAPK signaling inhibitors. Conclusion: Irisin exerts profound neuroprotective and anti-inflammatory effects on H/R-stimulated cerebral neurons by inhibiting the MAPK signaling activation. Therefore, irisin may serve as a potential drug for the treatment of patients with ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Stroke remains a leading cause of adult disability and the demand for stroke rehabilitation services is growing, and Astragaloside IV (As IV), a primary bioactive compound of Radix Astragali : Astragalus mongholicus Bunge (Fabaceae), may be a promising stroke therapy. Methods: To access the effect of As IV on adult mice after ischemic stroke, a photochemical ischemia model was established on C57BL/6 mice, which were intravenously administered As IV for three consecutive days later. And then the cognitive benefits and hippocampal neurogenesis were evaluated by Morris Water Maze (MWM) test, Golgi staining, and immunohistochemical staining in vivo and in vitro. Furthermore, to find out the underlying mechanism, interleukin-17 (IL-17) knockout (KO) mice were used, through RNA sequence (RNA-seq) analysis and immunohistochemistry. Then the mechanism of neurogenesis promoted by As IV was observed by western blot both in vivo and in vitro. Specifically, As IV, recombinant mouse IL-17A and IL-17F, and Wingless/integrated (Wnt)-expressing virus was administered respectively in neural stem cells (NSCs), and then their diameters and protein expression of Nestin, IL-17, and Wnt pathway relevant protein, were measured in vitro. Results: Administering As IV resulted in significant amelioration of stroke-induced cognitive deficits. And more hippocampal neurons with normal morphology, significant increments in the length of the apical dendrites, and the density of their spines were observed in As IV-treated mice. Furthermore, the immunohistochemistry staining of DCX/BrdU and Sox2/Nestin showed As IV could promote hippocampal neurogenesis and NSC proliferation after ischemic stroke, as well as in vitro. For the mechanism underlying, IL-17 expression was downregulated significantly by As IV treatment and knocking out IL-17 was associated with nervous regeneration and synapse repair according to the analysis of RNA-seq. Consistent to As IV treatment, knocking out IL-17 showed some promotion on hippocampal neurogenesis and proliferation of NSCs, with activating Wnt pathway after stoke. Finally, in vitro , NSCs' diameters and protein expression of Nestin, IL-17, and Wnt pathway were regulated by either administering As IV or inhibiting IL-17. Conclusion: As IV stimulates hippocampal neurogenesis after stroke, thus potentially facilitates brain to remodel and repair by downregulating IL-17 expression via Wnt pathway. [ABSTRACT FROM AUTHOR]

Background: Inflammatory response exerts an important role in ischemia/reperfusion (I/R) injury. TLR4 and myeloid differentiation factor 88 (MyD88) are key components in inflammation and are involved in the cerebral I/R injury. Irisin is a skeletal muscle-derived myokine produced after exercise, which was found to suppress inflammation. In this study, we investigated whether irisin could protect the brain from I/R injury through the TLR4/MyD88 pathway. Methods: Male Sprague Dawley rats (20 months, 190 ∼ 240 g) were pretreated with irisin at 10, 50, or 100 mg/kg for consecutive 3 days and then subjected to surgery of middle cerebral artery occlusion or sham operation. Infarct size and neuron loss were measured to evaluate brain damage. The mRNA and protein levels of TLR4 and MyD88 were measured by in situ hybridization and immunohistochemistry, respectively. NF-κB activation was assessed by electrophoretic mobility shift assay. Neurological function was evaluated by neurobehavior score test and passive avoidance test. Results: Irisin could reduce neuronal damage and neurofunctional impairment after I/R injury. This effect was mediated by downregulating the TLR4/MyD88 and inhibiting NF-κB activation. Conclusion: Irisin plays a beneficial effect in I/R injury through regulating the TLR4/MyD88 pathway. [ABSTRACT FROM AUTHOR]

• miR-665-3p was decreased by OGD in microglial cells. • miR-665-3p attenuated OGD-induced microglial apoptosis and inflammation. • TRIM8 was identified as a target gene of miR-655-3p. • miR-655-3p inhibited NF-κB activation by targeting TRIM8. Microglial inflammation induced by ischemic stroke aggravates brain damage. MicroRNAs (miRNAs) have emerged as pivotal regulators in ischemic stroke-induced inflammation in microglial cells. miR-665-3p has been reported as a critical inflammation-associated miRNA. However, whether miR-665-3p participates in regulating microglial inflammation during ischemic stroke is underdetermined. This study investigated the potential role of miR-665-3p in stroke-induced inflammation in microglial cells using a cellular model of oxygen-glucose deprivation (OGD)-stimulated microglial cells in vitro. We found that miR-665-3p expression was decreased in microglial cells exposed to OGD treatment. Functional experiments demonstrated that the overexpression of miR-665-3p attenuated OGD-induced apoptosis and inflammation in microglial cells. Notably, tripartite motif 8 (TRIM8) was identified as a target gene of miR-665-3p. TRIM8 expression was induced by OGD treatment in microglial cells and the knockdown of TRIM8 protected microglial cells from OGD -induced cytotoxicity and inflammation. Moreover, TRIM8 knockdown or miR-665-3p overexpression blocked OGD-induced activation of nuclear factor (NF)-κB signaling in microglial cells. In addition, TRIM8 overexpression partially reversed the miR-665-3p overexpression-mediated inhibitory effect on OGD-induced inflammation in microglial cells. Taken together, these results indicate that miR-665-3p up-regulation protects microglial cells from OGD-induced apoptosis and inflammatory response by targeting TRIM8 to inhibit NF-κB signaling. [ABSTRACT FROM AUTHOR]

Abstract With the speedy technological advances during the past few decades, human exposure to the electromagnetic field (EMF) has become increasingly common. Exposure to EMF may induce neural injuries and dysfunction of various organs, likely involving neuroinflammation and activation of microglial cells. Isoflurane preconditioning (IP) is shown to provide neuroprotection in various neurological diseases by inhibiting excessive neuroinflammatory responses. Brain samples harvested from rats exposed to electromagnetic pulse (EMP) with or without IP were subjected to qPCR, Western blot assay, and immunohistochemistry to determine the expression of pro-inflammatory/anti-inflammatory microglia markers and a variety of pro- and anti-inflammatory mediators. Suppressor of cytokine signaling 1 (SOCS1) siRNA was used in cultured N9 microglia cells to examine the roles of SOCS1 in the effect of IP. In both in vivo and in vitro experiments, EMP-exposed microglia were predominantly pro-inflammatory microglia, accompanied by increased expression of pro-inflammatory cytokines and chemokines, and activation of TLR4 pathway, leading to neuronal death. IP reversed the changes induced by EMP and switched the activated microglia to an anti-inflammatory phenotype. SOCS1 siRNA abolished the beneficial effects of IP. IP ameliorates EMP-induced neural injuries by shifting microglia polarization from pro-inflammatory to anti-inflammatory phenotype via upregulation of SOCS1. Highlights • SOCS1 siRNA abolishes the beneficial effects of IP. • IP ameliorates EMP-induced neural injuries. • IP shifts microglia polarization from pro-inflammatory to anti-inflammatory phenotype via upregulation of SOCS1. [ABSTRACT FROM AUTHOR]

Objective: A number of trials have shown that remote ischemic preconditioning (RIPC) could reduce lung injury of patients suffering cardiovascular surgery, pulmonary transplantation surgery and thoracic surgery with one-lung ventilation. However, there is still a controversy over the lung protection of RIPC in patients who suffers different types of surgery. We undertook meta-analysis of the randomized controlled trials to evaluate the effect of remote ischemic preconditioning on clinical outcomes of patients with lung injury.Design: Systematic review and meta-analysis.Setting: Perioperative care areas.Patients: Adults and infants suffering cardiovascular surgery with lung injury.Intervention: Remote ischemic preconditioning.Measurements: The literatures were selected complying with the inclusive and exclusive criteria from the following databases as PubMed, Embase, Medline, Chinese Biomedical Literature and Journal Databases, Chinese Academic and VIP journal full-text Databases. Inclusion criteria includes: (1) Human clinical randomized and controlled trial; (2) the article we included is a clinical randomized controlled study; (3) the article discusses the effect of RIPC on lung injury of patients; (4) the primary evaluation indicators of the inclusive studies included postoperative intensive care unit stay time and mechanical ventilation time; (5) published in the form of full text, any language; (6) the type of operation is cardiovascular surgery; (7) there is no serious COPD, ARDS, respiratory failure and other lung diseases. Articles were excluded if they reported none of the outcomes as follows: postoperative intensive care unit stay time and mechanical ventilation time, human clinical controlled trails, pulmonary protection of RIPC, prospective clinical controlled trials. Two independent reviewers screened abstracts and titles, and selected records following full-text review. Software RevMan5.3 and STATA 12.0 were adopted to perform Meta-analysis.Result: The search finally includes10 studies of 708 patients, 352 patients in RIPC group and 356 patients in control group. The baseline characteristics of patients are no differences in two groups (P > 0.05). Compared with control group, RIPC significantly reduced the duration of ICU (P < 0.05) and mechanical ventilation time (P < 0.05) in RIPC group. In addition, the serum TNF-α and MDA concentration 24 h after operation in RIPC group are significantly lower than control group (P < 0.05). However, there are no significant differences between RIPC group and control group in terms of serum IL-6, IL-8 concentrations, A-aDO2, PaO2/FiO2 and respiratory index 24 h after operation.Conclusion: RIPC can decrease pulmonary inflammatory responses, reduce the duration of ICU and mechanical ventilation time, and improve the clinical outcomes of patients with lung injury. [ABSTRACT FROM AUTHOR]