Dexmedetomidine Protects Against Traumatic Brain Injury-Induced Acute Lung Injury in Mice

Wang, Yuanyuan; Wang, Changli; Zhang, Dan; Bo, Lulong; Deng, Xiaoming

doi:10.12659/msm.908133

Cited by 15 publications

(8 citation statements)

References 27 publications

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“…provided us with notable insights into the neuroprotective effect of Dex [4,7,10,15,[29][30][31][32][33][34]. In this study, the expressions of IL-1b, TNF-a, IL-6, and IL-8 were significantly suppressed in the Dex group when compared to the I/R group, indicating that Dex plays a clear anti-inflammatory role in amelioration of cerebral I/R injury.…”

Section: Animal Studymentioning

confidence: 52%

Dexmedetomidine Post-Conditioning Alleviates Cerebral Ischemia-Reperfusion Injury in Rats by Inhibiting High Mobility Group Protein B1 Group (HMGB1)/Toll-Like Receptor 4 (TLR4)/Nuclear Factor kappa B (NF-κB) Signaling Pathway

et al. 2020

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Departmental sources Background: Cerebral ischemia-reperfusion injury is a pivotal cause of deaths due to cerebrovascular accident. Increased research efforts are needed to reveal the mechanism underlying its aggravation or alleviation. In this study, the effects of dexmedetomidine post-conditioning on the HMGB1/TLR4/NF-kB signaling pathway in cerebral ischemia-reperfusion rats was explored. Material/Methods: Ninety rats were randomly divided into 5 groups-a sham group (Sham), a model group (I/R), a dexmedetomidine post-conditioning group (Dex), a recombinant high mobility group protein B1 group (rHMGB1), and a recombinant HMGB1+dexmedetomidine post-conditioning group (rHMGB1+Dex)-with 18 rats in each group. Longa grading, wet-dry weighing, TTC staining, HE staining, and immunohistochemical staining were used to assess brain damage. ELISA, RT-PCR, and Western blot analyses were performed to assess expression of IL-1b, TNF-a, IL-6, IL-8, HMGB1, TLR4, and NF-kB. Results: Compared with the I/R group, the neurological function score, brain water content, infarction area, and the number of COX-2-and IBA-1-positive cells in the Dex group were significantly lower, accompanied by downregulated expression of the HMGB1/TLR4/NF-kB pathway, alleviated inflammation, and oxidative stress injury in brain tissue. These trends were mostly reversed in the rHMGB1 group and rHMGB1+Dex group, but not in the Dex group. Furthermore, when compared to the Dex group, there were significant increases of H 2 O 2 , MDA, NO, IL-1b, TNF-a, IL-6, IL-8, HMGB1, TLR4, and p-P65 in the rHMGB1 group and rHMGB1+Dex group, in which a significant decrease of T-AOC, SOD, and p-IkBa was also detected. Conclusions: Dexmedetomidine post-conditioning can alleviate cerebral ischemia-reperfusion injury in rats by inhibiting the HMGB1/TLR4/NF-kB signaling pathway.

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Section: Animal Studymentioning

confidence: 52%

Dexmedetomidine Post-Conditioning Alleviates Cerebral Ischemia-Reperfusion Injury in Rats by Inhibiting High Mobility Group Protein B1 Group (HMGB1)/Toll-Like Receptor 4 (TLR4)/Nuclear Factor kappa B (NF-κB) Signaling Pathway

et al. 2020

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“…A previous study revealed that DEX significantly reduces mortality and decreases the levels of inflammatory cytokines during endotoxemia in rats [39]. DEX reduces sepsis-related acute lung injury and has a protective effect on ischemia-reperfusion injury of the heart, brain, kidneys, and intestine in animal model [40][41][42][43]. DEX affects the immune cell ratio and suppresses inflammatory cytokine production in spleen and lymphocytes [44].…”

Section: Discussionmentioning

confidence: 98%

Dexmedetomidine inhibits LPS-induced proinflammatory responses via suppressing HIF1α-dependent glycolysis in macrophages

Meng

Guo

Jiang

et al. 2020

Aging

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Dexmedetomidine, a highly selective α2-adrenoceptor agonist, has been reported to exert an anti-inflammatory effect in several animal models, but the mechanism remains unclear. Previous studies have shown that hypoxia inducible factor 1α-induced glycolysis is essential for the activation of inflammatory macrophages. However, whether dexmedetomidine influences hypoxia inducible factor 1α-induced glycolysis and thus exerts an antiinflammatory effect has been poorly investigated. This study aims to elucidate the anti-inflammatory mechanism of dexmedetomidine involving the hypoxia inducible factor 1α-dependent glycolytic pathway. We showed that dexmedetomidine could suppress lipopolysaccharide-induced inflammatory cytokine production; inhibit the extracellular acidification rate, glucose consumption and lactate production; and decrease the expression of glycolytic genes in macrophages. The enhancement of glycolysis by the granulocyte-macrophage colony-stimulating factor or higher concentration of glucose could reverse the anti-inflammatory effect of dexmedetomidine on lipopolysaccharide-treated macrophages. Moreover, dexmedetomidine significantly inhibited the upregulation of hypoxia inducible factor 1α at the mRNA and protein levels. Genetic inhibition of hypoxia inducible factor 1α expression could reverse the anti-inflammatory effect of dexmedetomidine. Taken together, our results indicate that dexmedetomidine attenuates lipopolysaccharide-induced proinflammatory responses partially by suppressing hypoxia inducible factor 1α-dependent glycolysis in macrophages.

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“…The mechanisms for the inhibition of autophagy may include the potent anti-inflammatory property of DEX. In a TBI-induced ALI mouse model, a single dose of 50 µg/kg DEX exerted protective effects via suppression of HMGB-1 signal transduction in the lung tissue [ 36 ]. A study in a rat model of sepsis-induced ALI revealed that treatment with 10–20 µg/kg DEX inhibited lung inflammation by suppressing the TLR4/MyD88/NFκB [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine attenuates subarachnoid hemorrhage-induced acute lung injury through regulating autophagy and TLR/NF-kappaB signaling pathway

Han

Lim

et al. 2022

Korean J Anesthesiol

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Background: Acute lung injury (ALI) is the most serious complication of subarachnoid hemorrhage (SAH). We investigated role of autophagy and inflammatory signaling pathways in lung damage and therapeutic effects of dexmedetomidine (DEX).Methods: Fifty male Wistar rats were randomly divided into five groups: sham, SAH, SAH+ DEX5, SAH+DEX25, and SAH+DEX50. SAH was induced using endovascular perforation technique. All rats received mechanical ventilation for 60 minutes. At 2 and 24 h of SAH induction, SAH+DEX groups were treated with 5, 25, and 50 µg/kg of dexmedetomidine, respectively.Histological ALI score and pulmonary edema were assessed after 48 hours. Lung expression of LC3B, ATG3, p62, TLR4, TLR9, and NFκB was assessed using western blotting and quantitative PCR. Blood levels of IL-6, IL-1β, IFN-γ, and TNFα were also assessed.Results: SAH induced ALI and pulmonary edema, which were attenuated in SAH+DEX5 (P<0.001 for both) and SAH+DEX25 groups (P=0.001 and P<0.001 for ALI and edema, respectively). Lung expressions of LC3B and ATG3 were upregulated in SAH group, which was attenuated in SAH+DEX5 and SAH+DEX25 groups. Lung expressions of TLR4, TLR9, and NFκB were increased in SAH group, which was attenuated in SAH+DEX5 group. Blood IL-6 level was increased in SAH group and attenuated in SAH+DEX5 and SAH+DEX25 groups. Blood IFN-γ level was lower in SAH group than in sham group, and it was increased in SAH+DEX25 group.Conclusions: Low-dose DEX treatment after SAH may protect against ALI by disrupting pathological brain-lung crosstalk and alleviating autophagy flux and TLR-dependent inflammatory pathways.

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Dexmedetomidine Protects Against Traumatic Brain Injury-Induced Acute Lung Injury in Mice

Cited by 15 publications

References 27 publications

Dexmedetomidine Post-Conditioning Alleviates Cerebral Ischemia-Reperfusion Injury in Rats by Inhibiting High Mobility Group Protein B1 Group (HMGB1)/Toll-Like Receptor 4 (TLR4)/Nuclear Factor kappa B (NF-κB) Signaling Pathway

Dexmedetomidine Post-Conditioning Alleviates Cerebral Ischemia-Reperfusion Injury in Rats by Inhibiting High Mobility Group Protein B1 Group (HMGB1)/Toll-Like Receptor 4 (TLR4)/Nuclear Factor kappa B (NF-κB) Signaling Pathway

Dexmedetomidine inhibits LPS-induced proinflammatory responses via suppressing HIF1α-dependent glycolysis in macrophages

Dexmedetomidine attenuates subarachnoid hemorrhage-induced acute lung injury through regulating autophagy and TLR/NF-kappaB signaling pathway

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