Dexmedetomidine preconditioning plays a neuroprotective role and suppresses TLR4/NF-κB pathways model of cerebral ischemia reperfusion

Wang, Shouliang; Duan, Lian; Xia, Bin; Liu, Zhifei; Wang, Yu; Wang, Gongming

doi:10.1016/j.biopha.2017.06.051

Cited by 62 publications

(31 citation statements)

References 21 publications

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“…I/R injury is a consequence of tourniquet application in extremity surgery. There is emerging evidence that DEX exerts a protective effect against I/R injury to the skeletal muscles, retina, spinal cord, lung, and certain remote organs . The cumulative protective effect of DEX results from a combination of its anti‐inflammatory, antioxidative, and apoptosis regulatory effects.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine protects against lung injury induced by limb ischemia‐reperfusion via the TLR4/MyD88/NF‐κB pathway

Xue

Chen

Tang

et al. 2019

The Kaohsiung J of Med Scie

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Dexmedetomidine (DEX) can protect the lung from ischemia-reperfusion (I/R) injury, but the underlying mechanisms are not fully understood. The aims of this study were to determine whether DEX attenuates lung injury following lower extremity I/R and to investigate the related toll-like receptor 4 (TLR4) signaling pathway. Twenty-eight SD rats were divided into four groups (n = 7): Sham, I/R, I/R + DEX (25 μg/kg prior to ischemia), and I/R + DEX + Atip (250 μg/kg atipamezole before DEX treatment). Lower extremity I/R was induced by left femoral artery clamping for 3 hours and followed by 2 hours reperfusion. Quantitative alveolar damage and the wet/dry (W/D) ratio were calculated. Interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)α in the bronchoalveolar lavage fluid (BALF) and serum and myeloperoxidase (MPO) in the lung were measured. The TLR4 and MyD88 mRNA expression levels were measured by RT-PCR, nuclear factor (NF)-κB, and phosphorylated NF-κB by western blot, respectively. Quantitative alveolar damage, W/D ratio, MPO, BALF and serum IL-1, IL-6, and TNF-α, and TLR4, MyD88, NF-κB, and p-NF-κB expression significantly increased in the I/R group relative to the Sham group. DEX preconditioning significantly reduced lung edema, and histological injury relative to the I/R group. Serum and BALF IL-1, IL-6, and TNF-α levels, MPO activity and TLR4, MyD88, NF-κB, and p-NF-κB expression were also significantly reduced in the I/R + DEX group compared with the I/R group. Atipamezole partially reversed all the aforementioned effects. DEX preconditioning protects the lungs against lower extremity I/R injury via α2-adrenoceptor-dependent and α2-adrenoceptor-independent mechanisms. It also suppresses the TLR4 pathway and reduces inflammation. K E Y W O R D S acute lung injury, dexmedetomidine, limb ischemia/reperfusion injury, toll-like receptor 4

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Section: Discussionmentioning

confidence: 99%

Dexmedetomidine protects against lung injury induced by limb ischemia‐reperfusion via the TLR4/MyD88/NF‐κB pathway

Xue

Chen

Tang

et al. 2019

The Kaohsiung J of Med Scie

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“…It has been confirmed by many experiments that TLR4 is relevant for the induction of inflammation. TLR4 participates in the whole pathological process of cerebral ischemia [26,27]. After cerebral ischemia, NF-κB can be found highly expressed in a variety of cells.…”

Section: Introductionmentioning

confidence: 99%

Salvianolic Acid D Alleviates Cerebral Ischemia-Reperfusion Injury by Suppressing the Cytoplasmic Translocation and Release of HMGB1-Triggered NF-κB Activation to Inhibit Inflammatory Response

Zhang

Song

Wan

et al. 2020

Mediators of Inflammation

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Inflammatory response participates in the overall pathophysiological process of stroke. It is a promising strategy to develop antistroke drugs targeting inflammation. This study is aimed at investigating the therapeutic effect and anti-inflammatory mechanism of salvianolic acid D (SalD) against cerebral ischemia/reperfusion (I/R) injury. A rat middle cerebral artery occlusion/reperfusion (MCAO/R) injury model was established, and an oxygen-glucose deprivation/reoxygenation (OGD/R) injury model was established in PC12 cells. Neurological deficit score, cerebral infarction, and edema were studied in vivo. Cell viability was achieved using the MTT method in vitro. The Bax, Bcl-2, cytochrome c, HMGB1, TLR4, TRAF6, NF-κB p65, p-NF-κB p65, and cleaved caspase-3 and -9 were tested via the Western blot method. Cytokines and cytokine mRNA, including TNF-α, IL-1β, and IL-6, were studied via ELISA and PCR methods. The translocation of HMGB1 and NF-κB were studied by immunofluorescence assay. The HMGB1/NeuN, HMGB1/GFAP, and HMGB1/Iba1 double staining was carried out to observe the localization of HMGB1 in different cells. Results showed that SalD alleviated neurological impairment, decreased cerebral infarction, and reduced edema in I/R rats. SalD improved OGD/R-downregulated PC12 cell viability. SalD also promoted Bcl-2 expression and suppressed Bax, cytochrome c, and cleaved caspase-3 and -9 expression. SalD decreased the intensity of TLR4, MyD88, and TRAF6 proteins both in vivo and in vitro, and significantly inhibited the NF-κB nuclear translocation induced by I/R and OGD/R. What’s more, SalD inhibited HMGB1 cytoplasmic translocation in neurons, astrocytes, and microglia in both the cortex and hippocampus regions of I/R rats. In conclusion, SalD can alleviate I/R-induced cerebral injury in rats and increase the PC12 cell viability affected by OGD/R. The anti-inflammatory mechanism of SalD might result from the decreased nuclear-to-cytoplasmic translocation of HMGB1 and the inhibition on its downstream TLR4/MyD88/NF-κB signaling.

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“…It appears to have a partial neuroprotective effect in animal models of cerebral ischemia (Luo et al, ). Mechanisms presented for dexmedetomidine neuroprotective effect include α2A adrenoreceptor subtypes, brain‐derived neurotrophic factors, phosphoinositide 3‐kinase (P13K)/Akt, and extracellular signal‐regulated protein kinase (ERK)1/2 pathways (Wang et al, ). However, clinical application of dexmedetomidine alone or as an adjunct to remifentanil for EITs have not been reported adequately, though several studies have described usefulness of dexmedetomidine with or without remifentanil for craniotomy, none of the studies explored dexmedetomidine neuroprotective effects during and after EITs (Yun et al, ).…”

Section: Introductionmentioning

confidence: 99%

Effect of intraoperative infusion of dexmedetomidine on postoperative recovery in patients undergoing endovascular interventional therapies: A prospective, randomized, controlled trial

Ren

et al. 2019

Brain and Behavior

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Background Rapid emergence from general anesthesia during endovascular interventional therapies (EITs) is important. However, the solution that improved quality of both analepsia and postoperative recovery after EITs has not been specifically addressed. We conducted this prospective, randomized, controlled trial to evaluate the intraoperative infusion of dexmedetomidine on quality of analepsia and postoperative recovery in patients undergoing EITs. Methods Eighty‐six patients undergoing EITs were divided into three groups: RD1 (dexmedetomidine at an initial dose of 0.5 μg/kg for 10 min adjusted to 0.2 μg kg−1 hr−1 throughout EIT), RD2 (dexmedetomidine at an initial dose of 0.5 μg/kg for 10 min adjusted to 0.4 μg kg−1 hr−1 throughout EIT), and RD3 (dexmedetomidine at an initial dose of 0.5 μg/kg for 10 min adjusted to 0.6 μg kg−1 hr−1 throughout EIT). An analgesia system delivered sufentanil only. The primary outcome measure was the total consumption of nimodipine during the first 48 hr after surgery. The secondary outcome measures were sufentanil consumption, pain intensity, hemodynamics, functional activity score (FAS), neurologic examination, level of sedation (LOS), and Bruggrmann comfort scale (BCS). We also recorded the intraoperative hemodynamic data, requirement of narcotic and vasoactive drugs, prevalence of complications and symptomatic cerebral vasospasm, duration of postanesthesia care unit (PACU) stay, Glasgow Outcome Score (GOS) at 3 months, and prevalence of cerebral infarction 30 days after surgery. Results Dexmedetomidine application in the regimen RD3 reduced the consumption of the total dose of nimodipine and sufentanil 48 hr after surgery, prevalence of symptomatic cerebral vasospasm, consumption of narcotic drugs and nimodipine during surgery, pain intensity during the first 8 hr after surgery, and increased both BCS during the first 4 hr after surgery and hemodynamic stability. However, the LOS was increased at the 0.5 hr after surgery and surgeon satisfaction score was lower. There were no significant differences among the groups for consumption of vasoactive drugs except urapidil, Glasgow coma scale (GCS) and FAS during the first 48 hr after surgery, GOS at 3 months, and cerebral infarction after 30 days. Conclusions Dexmedetomidine (an initial dose of 0.5 μg/kg for 10 min adjusted to 0.6 μg kg−1 hr−1 throughout EIT) could reduce the total consumption of nimodipine and opioid during the first 48 hr after surgery, the concerning adverse effects, and improve pain scores. The optimal dosage of dexmedetomidine during EITs merits further investigation.

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Dexmedetomidine preconditioning plays a neuroprotective role and suppresses TLR4/NF-κB pathways model of cerebral ischemia reperfusion

Cited by 62 publications

References 21 publications

Dexmedetomidine protects against lung injury induced by limb ischemia‐reperfusion via the TLR4/MyD88/NF‐κB pathway

Dexmedetomidine protects against lung injury induced by limb ischemia‐reperfusion via the TLR4/MyD88/NF‐κB pathway

Salvianolic Acid D Alleviates Cerebral Ischemia-Reperfusion Injury by Suppressing the Cytoplasmic Translocation and Release of HMGB1-Triggered NF-κB Activation to Inhibit Inflammatory Response

Effect of intraoperative infusion of dexmedetomidine on postoperative recovery in patients undergoing endovascular interventional therapies: A prospective, randomized, controlled trial

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