&lt;p&gt;Dexmedetomidine Attenuates Neuroinflammation In LPS-Stimulated BV2 Microglia Cells Through Upregulation Of miR-340&lt;/p&gt;

Yang, Bo; Zhu, Yijun; He, Guangbao; Ni, Hongwei; Liu, Chenxia; Ma, Limin; Zhang, Lifeng; Shi, Dan

doi:10.2147/dddt.s210511

Cited by 62 publications

(60 citation statements)

References 45 publications

(44 reference statements)

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“…Taken together, LMTK2 overexpression reduced the levels of iNOS, COX-2 and pro-inflammatory factors, TNF-α, IL-1β and IL-6, but increased IL-10 level; possibly due to the dependence of LPS-induced microglia on Nrf2 pathway. However, no significant changes were observed in IL-10 levels following LPS stimulation, which was consistent with a previous report (34). IL-10 is an important inflammatory suppressor in vivo and can inhibit the release of pro-inflammatory cytokines in microglia cells in the central nervous system (35).…”

Section: Discussionsupporting

confidence: 92%

LMTK2 regulates inflammation in lipopolysaccharide‑stimulated BV2 cells

et al. 2021

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Microglia activation plays vital roles in neuroinflammatory pathologys. Lemurs tyrosine kinase 2 (LMTK2) was reported to regulate NF-κB signals. In the present study, the roles of LMTK2 were investigated in lipopolysaccharide (LPS)-treated BV-2 cells. Reverse transcription-quantitative (RT-q)PCR and western blotting (WB) were utilized to analyze LMTK2 levels in LPS-treated BV2 cells. MTT assay determined cell viabilities. Nitric oxide (NO) and prostaglandin E2 (PGE2) levels were assessed through Griess and enzyme-linked immunosorbent assay (ELISA), respectively. The expression level of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected through RT-qPCR and WB. The release of inflammatory mediators under LPS stimulation, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-10, were analyzed through ELISA. WB was used to analyze the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1)/NAD(P)H dehydrogenase quinone 1 (NQO1) signal pathway. The results showed that the levels of the inflammatory mediators, iNOS, NO, COX-2 and PGE2, along with pro-inflammatory factors, TNF-α, IL-1β and IL-6, were significantly decreased following the induction of exogenous LMTK2 expression by LMTK2 overexpression plasmids in LPS-induced BV2 microglia. In contrast, anti-inflammatory factor IL-10 showed obvious decrease. Additionally, LMTK2 overexpression induced the elevation of Nrf2 in the cytoplasm and nucleus, along with the upregulation of HO-1 and NQO1 expression. In conclusion, LMTK2 is postulated to regulate neuroinflammation possibly through Nrf2 pathway. The present study is essential to reveal the underlying function of LMTK2 and to identify novel therapeutic targets for drug development in treating neuroinflammation.

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Section: Discussionsupporting

confidence: 92%

LMTK2 regulates inflammation in lipopolysaccharide‑stimulated BV2 cells

et al. 2021

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“…Similar to the results in the rat ICH model, miR-340-5p was detected to be downregulated in the cells treated with LPS. In addition, overexpression of miR-340-5p eliminated the effect of LPS on the secretion of proinflammatory cytokines, which was consistent with the previous evidence [23]. This evidence suggested the anti-inflammatory effect of miR-340-5p on ICH-induced brain injury in vivo.…”

Section: Discussionsupporting

confidence: 91%

“…Therefore, neuroinflammation is regarded as a pivotal target for ICH treatment. miR-340-5p has been proposed to exert an anti-inflammatory effect in several human diseases [23, 24]. As Gao et al suggested, overexpression of miR-340-5p could suppress inflammatory response as well as the production of IL-1β, TNF-α, and IL-6 in the model of chronic constriction injury [24].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have demonstrated that microglia can be activated by ICH which contributes to the secretion of proinflammatory cytokines during the occurrence of disease [27]. Recently, miR-340-5p was determined to be involved in the anti-inflammatory effects of dexmedetomidine in the nervous system, and overexpression of miR-340-5p enhanced the protective effect of dexmedetomidine in LPS-stimulated BV-2 cells [23]. In the present study, LPS-induced microglial cells were recruited to investigate the role of miR-340-5p in inflammatory response induced by ICH in vitro.…”

Section: Discussionmentioning

confidence: 99%

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Protective Effect of miR-340-5p against Brain Injury after Intracerebral Hemorrhage by Targeting PDCD4

Zhou

Huang

et al. 2020

Cerebrovasc Dis

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Objective: Intracerebral hemorrhage (ICH) is a common cerebrovascular disease. Increasing evidence has documented the crucial role of microRNAs in ICH. The present study aimed to investigate the role and underlying mechanism of miR-340-5p in ICH. Methods: The collagenase-induced ICH rat model was established. The neurological function of rats and the cerebral water content of rat brain tissue were measured to assess the brain injury. BV-2 cells were recruited and treated by LPS to mimic ICH-induced inflammatory response. qRT-PCR was used for the measurement of miR-340-5p. The protein levels of TNF-α, IL-6, and IL-1β were detected using ELISA. Luciferase reporter gene assay was performed to confirm the target gene. Results: Downregulation of miR-340-5p was detected in the serum of ICH patients and the brain tissues of ICH rats. Overexpression of miR-340-5p reversed the influence of ICH on the neurological function score and cerebral water content and inhibited the production of proinflammatory cytokines (TNF-α, IL-6, and IL-1β), which were induced by ICH in vivo. In in vitro study, levels of TNF-α, IL-6, and IL-1β were significantly enhanced in cells after LPS treatment, but these increases were eliminated by overexpression of miR-340-5p. PDCD4 was a direct target gene of miR-340-5p. Conclusion: miR-340-5p protects against brain injury after ICH. miR-340-5p might exert an anti-inflammatory effect during the occurrence of ICH via targeting PDCD4.

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“…Dexmedetomidine has been widely used as an adjuvant of general anesthesia in patients undergoing cardiac and major non-cardiac surgeries or as a sedative in severe patients in ICU owing to its pharmacological functions of sedation, analgesia, anti-inflammation, and antioxidation [39][40][41]. The dexmedetomidine infusion in this study will begin between the completion of central venous catheterization and the onset of surgery and be maintained until the end of surgery.…”

Section: Discussionmentioning

confidence: 99%

Effect of intraoperative dexmedetomidine infusion on delirium in adult patients following cardiac valve surgery: a protocol of a randomized, double-blinded, and placebo-controlled study

Wang

Zhang

et al. 2020

Trials

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Background: Delirium is an acute status of brain dysfunction that commonly occurs in patients who have undergone cardiac surgery, and increases morbidity and mortality. It is associated with risk factors, such as older age, use of narcotics, cardiopulmonary bypass, and hypothermia. Dexmedetomidine infusion might exert a neuroprotective effect. However, the effect of perioperative administration of dexmedetomidine on the incidence of postoperative delirium (POD) in patients undergoing cardiac or non-cardiac surgery is yet controversial. The present study aimed to reveal the effect of intraoperative dexmedetomidine administration on the incidence of delirium in adult patients following cardiac surgery. Methods: This single-center, randomized, double-blinded, and placebo-controlled trial consisted of 652 patients randomly divided into two groups: dexmedetomidine and placebo. 0.6 μg/kg dexmedetomidine will be infused 10 min after central vein catheterization, followed by a continuous infusion at a speed of 0.4 μg/kg/h until the end of surgery in the dexmedetomidine group, while normal saline will be administered at the same rate in the placebo group. The primary outcome is the incidence of POD during the first 7 days post-surgery. The secondary outcomes include duration of mechanical ventilation after surgery, duration of stay in the intensive care unit and the hospital after surgery, incidence of hypotension during or after dexmedetomidine infusion, acute kidney injury and sudden arrhythmia during the hospital stay postoperatively, and all-cause mortality in 30 and 90 days after surgery, respectively. Discussion: This study was approved by the Ethics Committee of the Chinese Academy of Medical Sciences Fuwai Hospital on 6 March 2019 (2019-1180). The results will be disseminated at academic conferences and submitted to peer-reviewed publications. Either positive or negative results will provide guidance for clinical practice.

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<p>Dexmedetomidine Attenuates Neuroinflammation In LPS-Stimulated BV2 Microglia Cells Through Upregulation Of miR-340</p>

Cited by 62 publications

References 45 publications

LMTK2 regulates inflammation in lipopolysaccharide‑stimulated BV2 cells

LMTK2 regulates inflammation in lipopolysaccharide‑stimulated BV2 cells

Protective Effect of miR-340-5p against Brain Injury after Intracerebral Hemorrhage by Targeting PDCD4

Effect of intraoperative dexmedetomidine infusion on delirium in adult patients following cardiac valve surgery: a protocol of a randomized, double-blinded, and placebo-controlled study

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