Dexmedetomidine inhibits inflammatory response and autophagy through the circLrp1b/miR-27a-3p/Dram2 pathway in a rat model of traumatic brain injury

Li, Hengchang; Lu, Chengxiang; Yao, Wenfei; Xu, Lianyong; Zhou, Jun; Zheng, Bin

doi:10.18632/aging.103975

Cited by 50 publications

(55 citation statements)

References 55 publications

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“…Primary brain injuries lead to brain tissue disorganization, intracerebral hemorrhage and blood-brain barrier (BBB) damage, which is a direct physical injury to brain tissue that is difficult to prevent and usually cannot be reversed. Secondary brain injury, including calcium overload, oxidative stress, neuroinflammation, autophagy, lipid peroxidation and apoptosis, can be reversed ( 12 , 13 ).…”

Section: Introductionmentioning

confidence: 99%

“…Autophagy is the main cellular lysosomal degradation mechanism for degrading and recycling intracellular proteins and organelles under different physiological and pathological conditions ( 14 ). Autophagy has been reported to have a core role in many central nervous system diseases, including acute brain injury ( 12 , 15 , 16 ), intracerebral hemorrhage ( 17 ), subarachnoid hemorrhage (SAH) ( 18 ) and Huntington's disease ( 19 ). Tang et al ( 15 ) reported significant decreases in neural apoptosis and necrotic cell death following autophagy was inhibited by fibroblast growth factor-2 and the autophagy activator rapamycin aggravated brain injury.…”

Section: Introductionmentioning

confidence: 99%

“…Dexmedetomidine (DEX) is a highly selective α-2-adrenergic receptor agonist that provides sedation and analgesic effects with minimal respiratory depression ( 20 ). It is widely used in surgical procedures and to prevent postoperative delirium ( 12 , 21 ). Recent studies have confirmed that DEX exerts its protective effects on various organ injuries ( 12 , 20 ).…”

Section: Introductionmentioning

confidence: 99%

“…It is widely used in surgical procedures and to prevent postoperative delirium ( 12 , 21 ). Recent studies have confirmed that DEX exerts its protective effects on various organ injuries ( 12 , 20 ). Based on accumulating evidence, DEX also improves neurological function and delirium in patients ( 21 ) and alleviates EBI in the TBI model and the effect of DEX is dose-dependent ( 12 , 22 , 23 ).…”

Section: Introductionmentioning

confidence: 99%

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Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway

Feng

Zhu

et al. 2021

Mol Med Rep

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Traumatic brain injury (TBI) is a major public health problem and a major cause of mortality and disability that imposes a substantial economic burden worldwide. Dexmedetomidine (DEX), a highly selective α-2-adrenergic receptor agonist that functions as a sedative and analgesic with minimal respiratory depression, has been reported to alleviate early brain injury (EBI) following traumatic brain injury by reducing reactive oxygen species (ROS) production, apoptosis and autophagy. Autophagy is a programmed cell death mechanism that serves a vital role in neuronal cell death following TBI. However, the precise role of autophagy in DEX-mediated neuroprotection following TBI has not been confirmed. The present study aimed to investigate the neuroprotective effects and potential molecular mechanisms of DEX in TBI-induced EBI by regulating neural autophagy in a C57BL/6 mouse model. Mortality, the neurological score, brain water content, neuroinflammatory cytokine levels, ROS production, malondialdehyde levels and neuronal death were evaluated by TUNEL staining, Evans blue extravasation, ELISA, analysis of ROS/lipid peroxidation and western blotting. The results showed that DEX treatment markedly increased the survival rate and neurological score, increased neuron survival, decreased the expression of the LC3, Beclin-1 and NF-κB proteins, as well as the cytokines IL-1β, IL-6 and TNF-α, which indicated that DEX-mediated inhibition of autophagy and neuroinflammation ameliorated neuronal death following TBI. The neuroprotective capacity of DEX is partly dependent on the ROS/nuclear factor erythroid 2-related factor 2 signaling pathway. Taken together, the results of the present study indicated that DEX improves neurological outcomes in mice and reduces neuronal death by protecting against neural autophagy and neuroinflammation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway

Feng

Zhu

et al. 2021

Mol Med Rep

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“…The present study firstly found that DEX could reverse OGD-induced hepatocyte injury through regulation of TUG1/miR-194/ SIRT1 signaling pathway, further supplementing the mechanism by which DEX mediated the protection against of liver injury. It has been previously reported that DEX can act as an anti-inflammatory agent [28,29]. For instance, Feng Z et al found DEX attenuated the inflammatory responses in fatty liver disease [30].…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine hydrochloride inhibits hepatocyte apoptosis and inflammation by activating the lncRNA TUG1/miR-194/SIRT1 signaling pathway

Xiao-hong

Liao

et al. 2021

J Inflamm

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Background Liver injury seriously threatens the health of people. Meanwhile, dexmedetomidine hydrochloride (DEX) can protect against liver injury. However, the mechanism by which Dex mediates the progression of liver injury remains unclear. Thus, this study aimed to investigate the function of DEX in oxygen and glucose deprivation (OGD)-treated hepatocytes and its underlying mechanism. Methods In order to investigate the function of DEX in liver injury, WRL-68 cells were treated with OGD. Cell viability was measured by MTT assay. Cell apoptosis was detected by flow cytometry. Inflammatory cytokines levels were measured by ELISA assay. The interaction between miR-194 and TUG1 or SIRT1 was detected by dual-luciferase reporter. Gene and protein levels were measured by qPCR or western blotting. Results DEX notably reversed OGD-induced inflammation and apoptosis in WRL-68 cell. Meanwhile, the effect of OGD on TUG1, SIRT1 and miR-194 expression in WRL-68 cells was reversed by DEX treatment. However, TUG1 knockdown or miR-194 overexpression reversed the function of DEX in OGD-treated WRL-68 cells. Moreover, TUG1 could promote the expression of SIRT1 by sponging miR-194. Furthermore, knockdown of TUG1 promoted OGD-induced cell growth inhibition and inflammatory responses, while miR-194 inhibitor or SIRT1 overexpression partially reversed this phenomenon. Conclusions DEX could suppress OGD-induced hepatocyte apoptosis and inflammation by mediation of TUG1/miR-194/SIRT1 axis. Therefore, this study might provide a scientific basis for the application of DEX on liver injury treatment.

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Knockdown of miR‐19a suppresses gastrointestinal dysmotility diarrhea after TBI by regulating VIP expression

Zhang

et al. 2023

Brain and Behavior

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Background and aims: Traumatic brain injury (TBI) is the main cause of death and can lead to a variety of physiological complications, including gastrointestinal dysfunction.The present study aimed to confirm the miR-19a-mediated suppression of diarrhea after TBI through the regulation of VIP expression.Methods: A rat model of TBI induced by controlled cortical injury was used to observe gastrointestinal morphology by opening the abdomen after TBI. After 72 h of injury, the fecal water content of the rats was measured. The end ileal segments were removed, and HE staining was used to observe the histopathological changes in the intestine. The levels of serum miR-19a and VIP mRNA were detected by qRT-PCR. ELISA was performed to detect VIP levels in serum. Immunohistochemistry was used to detect the level of VIP in ileal tissues, and immunofluorescence was used to detect c-kit expression in ileal tissue. CCK-8 assay was used to detect the cell viability of interstitial cells of Cajal (ICCs), and TUNEL assay was used to detect apoptosis of ICCs.Results: miR-19a and VIP were highly expressed in the serum of TBI rats, and the knockdown of miR-19a alleviated TBI-induced diarrhea. In addition, the overexpression of miR-19a or VIP inhibited the proliferation of ICCs, promoted apoptosis, and suppressed intracellular Ca 2+ levels, whereas miR-19a suppression had the opposite effects. A nonselective nitric oxide synthase inhibitor (L-NA), PKG inhibitors (KT-5823 and RP-8CPT-cGMPS), and a guanylate cyclase inhibitor (ODQ) restored the inhibitory effects of VIP on ICC proliferation, anti-apoptosis effects, and Ca 2+ concentrations.Ying An and Sheng Hu contributed equally to this study.

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Dexmedetomidine inhibits inflammatory response and autophagy through the circLrp1b/miR-27a-3p/Dram2 pathway in a rat model of traumatic brain injury

Cited by 50 publications

References 55 publications

Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway

Dexmedetomidine alleviates early brain injury following traumatic brain injury by inhibiting autophagy and neuroinflammation through the ROS/Nrf2 signaling pathway

Dexmedetomidine hydrochloride inhibits hepatocyte apoptosis and inflammation by activating the lncRNA TUG1/miR-194/SIRT1 signaling pathway

Knockdown of miR‐19a suppresses gastrointestinal dysmotility diarrhea after TBI by regulating VIP expression

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