Dexmedetomidine post-treatment induces neuroprotection via activation of extracellular signal-regulated kinase in rats with subarachnoid haemorrhage

Wang, Y.; Han, Ruquan; Zuo, Zhiyi

doi:10.1093/bja/aev549

Cited by 55 publications

(38 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, the neuroprotection of dexmedetomidine from I/R‐induced injury to neuronal cells takes place via an anti‐apoptotic pathway. Recent studies reported that dexmedetomidine might have the potential at protection against experimental spinal cord injury and subarachnoid hemorrhage‐induced brain damage [Cosar et al, ; Gul et al, ; Wang et al, ]. In addition, dexmedetomidine could defend intestine, myocardial, renal, lung, cerebral and liver from reperfusion injury via an antiapoptotic pathway [Cai et al, ; Cui et al, ; Scott, ].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, dexmedetomidine is received wide attraction because of its potential at neuroprotection. Accompanied by cerebral vasospasm, subarachnoid hemorrhage is a serious condition, and dexmedetomidine is shown to defend against subarachnoid hemorrhage‐induced brain injuries through activating mitogen‐activated protein kinases (MAPK) in rats [Cosar et al, ; Wang et al, ]. In addition, Gul et al [] reported the effectiveness of dexmedetomidine in experimental spinal cord injury.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Protection of Dexmedetomidine Against Ischemia/Reperfusion-Induced Apoptotic Insults to Neuronal Cells Occurs Via an Intrinsic Mitochondria-Dependent Pathway

Tai

Tsai

et al. 2017

J. Cell. Biochem.

View full text Add to dashboard Cite

Dexmedetomidine, an agonist of alpha2-adrenergic receptors, is used for critically ill patients to induce and maintain sedation and analgesia. Brain ischemia/reperfusion (I/R) usually causes severe neuronal injuries to intensive care unit patients. This study was aimed to evaluate the effects of dexmedetomidine on I/R-induced insults to neuronal cells and the possible mechanisms. Treatment of neuro-2a cells with dexmedetomidine did not affect cell viability but could protect against I/R-induced cell death. Separately, the I/R-triggered cell shrinkage, DNA fragmentation, and apoptosis in neuro-2a cells were alleviated by dexmedetomidine. As to the mechanisms, exposure of neuro-2a cells to dexmedetomidine substantially attenuated I/R-induced translocation of Bax protein from the cytosol to mitochondria and reduction in the mitochondrial membrane potential (MMP). Successively, dexmedetomidine decreased cytochrome c release from mitochondria to the cytoplasm and consequent cascade activations of caspases-9, -3, and -6 in I/R-treated neuro-2a cells. Interestingly, downregulating caspase-6 activity synergistically improved dexmedetomidine-induced defense against I/R-induced apoptosis of neuro-2a cells. The dexmedetomidine-involved neuroprotection was further confirmed in the other NB41A3 neuronal cells by significantly attenuating I/R-induced changes in the MMP, caspase-3 activation, DNA fragmentation, and cell apoptosis. Taken together, this study has shown the neuroprotective effects of dexmedetomidine against I/R-induced apoptotic insults via an intrinsic Bax-mitochondria-cytochrome c-caspase protease pathway. J. Cell. Biochem. 118: 2635-2644, 2017. © 2016 Wiley Periodicals, Inc.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Protection of Dexmedetomidine Against Ischemia/Reperfusion-Induced Apoptotic Insults to Neuronal Cells Occurs Via an Intrinsic Mitochondria-Dependent Pathway

Tai

Tsai

et al. 2017

J. Cell. Biochem.

View full text Add to dashboard Cite

show abstract

“…Dexmedetomidine is a highly selective α 2 -adrenoreceptor agonist with sedative, anxiolytic, and analgesic effects [14, 15]. It also exhibits neuroprotective properties [16], anti-inflammatory benefits [17], and protective effects on the myocardium [18], against ischemia or reperfusion in the brain [19], and against lung [20], kidney [21], and liver injuries [22, 23]. In patients undergoing percutaneous RFA of small HCCs under general anesthesia with sevoflurane, it is unclear whether dexmedetomidine exhibits outstanding advantages over remifentanil in terms of pain management, or if it could be an alternative to remifentanil.…”

Section: Introductionmentioning

confidence: 99%

Comparison of dexmedetomidine vs. remifentanil combined with sevoflurane during radiofrequency ablation of hepatocellular carcinoma: a randomized controlled trial

Pan

et al. 2019

Trials

View full text Add to dashboard Cite

BackgroundRemifentanil is widely used for ultrasound-guided percutaneous radiofrequency ablation (RFA) of small hepatocellular carcinoma (HCC). We determined whether dexmedetomidine could be an alternative to remifentanil for RFA of HCC under general anesthesia with sevoflurane.MethodsWe prospectively randomized patients scheduled to undergo RFA for HCC to a dexmedetomidine (DEX) group or remifentanil (REMI) group (47 patients each). In the DEX group, a bolus infusion (0.4 μg kg− 1) was started 15 min before anesthesia induction and continued at 0.2 μg kg− 1 h− 1 until 10 min before the end of surgery. In the REMI group, 3 μg kg− 1 h− 1 of remifentanil was administered from 15 min before anesthesia induction to the end of the surgery. The primary endpoint was postoperative pain intensity. Secondary endpoints included analgesic requirement, postoperative liver function, patient comfort, and hemodynamic changes. Group allocation was concealed from patients and data analysts but not from anesthesiologists.ResultsPostoperative pain intensity, analgesic consumption, comfort, liver function, and time to emergence and extubation did not differ between the two groups. Heart rate, but not mean arterial pressure, was significantly lower in the DEX group than in the REMI group, at 1 min after intubation and from 30 min after the start of the surgery until anesthesia recovery. Sevoflurane concentration and dosage were significantly lower in the DEX group than in the REMI group.ConclusionDuring RFA for HCC, low-dose dexmedetomidine reduced the heart rate and need for inhalational anesthetics, without exacerbating postoperative discomfort or liver dysfunction. Although it did not exhibit outstanding advantages over remifentanil in terms of pain management, dexmedetomidine could be a safe alternative adjuvant for RFA under sevoflurane anesthesia.Trial registrationChinese Clinical Trial Registry, ChiCTR-OPC-15006613. Registered on 16 June 2015.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-3010-z) contains supplementary material, which is available to authorized users.

show abstract

“…Thus, the functional inactivation of RASSF1A results in failure of inhibiting effect on tumor cells. Researchers have detected the expression levels of p16 and RASSF1A mRNA in non-small cell lung carcinoma and found that their expression levels are distinctly down-regulated [6,7]. Therefore, blocking ERK signal pathway, down-regulating Dnmts and its protein expression levels, and up-regulating p16 and Ras mRNA and its protein expression levels can exert an inhibitory effect on the proliferation and growth of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Regulatory mechanism of extracellular signal-regulated kinase signal pathway for DNA methylation in lung carcinoma cells

Sun¹,

Liu²,

Liu³

et al. 2018

biomedicalresearch

View full text Add to dashboard Cite

Objective: This study aimed to discuss the regulatory mechanism of Extracellular Signal-Regulated Kinase (ERK) signal pathway for DNA methylation in lung carcinoma cells. Methodology: Human lung carcinoma cells were cultured, and the cells in logarithmic phase were inoculated in 96-hole plates and divided into three groups A-C. Six complex holes were present in each group. Phosphoric buffer salt solution, agonist epidermal growth factor, and blocker U1026 solution of ERK pathway were added into groups A-C, with a total amount of 25 μmol/L. Then, they were continuously treated for 48 h. Methyl thiazol tetrazolium method was used to determine cell proliferation rate. Fluorescent quantitative Polymerase Chain Reaction (qPCR) method was used to test the expression quantities of DNA transmethylase 1 (Dnmt1), DNA transmethylase 3a (Dnmt3a), DNA transmethylase 3b (Dnmt3b), tumor suppressor gene (p16), and Ras association domain family gene (RASSF1A) mRNA. Results: Significant differences exist among groups A-C in cell proliferation rate, as well as in Dnmt1, Dnmt3a, Dnmt3b, p16, and RASSF1A mRNA, and their protein expression levels (P<0.05). Cell proliferation rate and the expression quantities of Dnmt1, Dnmt3a, and Dnmt3b mRNA and their protein expression levels in group B were significantly higher than those in groups A and C (P<0.05). By contrast, the expression quantities of p16 and RASSF1A mRNA and their protein expression levels were significantly lower than those in groups A and C (P<0.05). Cell proliferation rate and the expression quantities of Dnmt1, Dnmt3a, and Dnmt3bmRNA and their protein expression levels in group A were significantly higher than those in group C (P<0.05). Conclusion: ERK signal pathway blocked both proliferation rate of lung carcinoma cells and DNA methylation level because of the down-regulation of Dnmts mRNA and their protein expression levels and the up-regulation of cancer suppressor genes p16 and RASSF1A mRNA and their protein expression levels.

show abstract

Dexmedetomidine post-treatment induces neuroprotection via activation of extracellular signal-regulated kinase in rats with subarachnoid haemorrhage

Abstract: Dexmedetomidine post-treatment provides neuroprotection against SAH. This effect appears to be mediated by ERK.

Cited by 55 publications

References 36 publications

Protection of Dexmedetomidine Against Ischemia/Reperfusion-Induced Apoptotic Insults to Neuronal Cells Occurs Via an Intrinsic Mitochondria-Dependent Pathway

Protection of Dexmedetomidine Against Ischemia/Reperfusion-Induced Apoptotic Insults to Neuronal Cells Occurs Via an Intrinsic Mitochondria-Dependent Pathway

Comparison of dexmedetomidine vs. remifentanil combined with sevoflurane during radiofrequency ablation of hepatocellular carcinoma: a randomized controlled trial

Regulatory mechanism of extracellular signal-regulated kinase signal pathway for DNA methylation in lung carcinoma cells

Contact Info

Product

Resources

About