Dexmedetomidine Inhibits Inflammation to Alleviate Early Neuronal Injury via TLR4/NF-κB Pathway in Rats with Traumatic Brain Injury

Huang, Guirong; Hao, Fengguan

doi:10.1615/critreveukaryotgeneexpr.2021037390

Cited by 11 publications

(14 citation statements)

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“…As shown in the present study, DEX alleviated neuroinflammation in mouse TBI models. Additionally, DEX directly regulates several cell death models (22,25,(48)(49)(50)(51). According to Gao et al (49), DEX induces the expression of the neuroglobin protein in hippocampal tissues and then inhibits neuronal apoptosis through the mitochondrial pathway.…”

Section: Discussionmentioning

confidence: 99%

“…As previous studies have identified a vital role for neuroinflammation in EBI following TBI, increased neuroinflammation aggravates EBI (12,20,22,24). The inflammatory complex induces the secretion of pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α and the subsequent activation of pro-inflammatory signaling through NF-κB to initiate pyroptosis.…”

Section: Dex Alleviates Neuroinflammation Following Tbimentioning

confidence: 98%

“…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 ). Huang and Hao ( 22 ) report that DEX relieves early brain injury (EBI) by inhibiting inflammation and decreasing neuronal apoptosis, which may depend on the TLR4/NF-κB signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

“…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 ). Huang and Hao ( 22 ) report that DEX relieves early brain injury (EBI) by inhibiting inflammation and decreasing neuronal apoptosis, which may depend on the TLR4/NF-κB signaling pathway. Li et al ( 24 ) also report that DEX alleviates EBI by inhibiting inflammation through the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.…”

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: Discussionmentioning

confidence: 99%

Section: Dex Alleviates Neuroinflammation Following Tbimentioning

confidence: 98%

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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“…Hydrogen-rich saline alleviates neuroinflammation after TBI. Previous studies have demonstrated that neuroinflammation exhibits a vital function in EBI after TBI and enhanced neuroinflammation can aggravate EBI (10,(47)(48)(49). Activation of the inflammatory process can induce the release of inflammatory cytokines, which include NF-κB, TNF-α IL-6 and IL-1β (39,50).…”

Section: Hydrogen-rich Saline Alleviates Neuronal Necroptosis After Tbimentioning

confidence: 99%

Hydrogen‑rich saline alleviates early brain injury through inhibition of necroptosis and neuroinflammation via the ROS/HO‑1 signaling pathway after traumatic brain injury

Feng

Chen

et al. 2021

Exp Ther Med

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Traumatic brain injury (TBI) has been recognized as a serious public health issue and a key contributor to disability and death, with a huge economic burden worldwide. Hydrogen, which is a slight and specific cytotoxic oxygen radical scavenger, has been demonstrated to ameliorate early brain injury (EBI) through reactive oxygen species (ROS), oxidative stress injury, apoptosis and necroptosis. Necroptosis refers to a type of programmed cell death process that has a vital function in neuronal cell death following TBI. The specific function of necroptosis in hydrogen-mediated neuroprotection after TBI, however, has yet to be determined. The present study aimed to examine the neuroprotective effects and possible molecular basis that underly hydrogen-rich saline in TBI-stimulated EBI by examining neural necroptosis in the C57BL/6 mouse model. The brain water content, neurological score, neuroinflammatory cytokines (NF-κΒ, TNF-α, IL-6 and IL-1β) and ROS were evaluated using flow cytometry. Malondialdehyde, superoxide dismutase (SOD) and glutathione (GSH) levels were evaluated using a biochemical kit. Receptor-interacting protein kinase (RIP)1, RIP3, Nrf2 and Heme oxygenase-1 (HO-1) were evaluated using western blotting. mRNA of Nrf2 and HO-1 were evaluated using quantitative PCR. Neuronal death was evaluated by TUNEL staining. The outcomes illustrated that hydrogen-rich saline treatment considerably enhanced the neurological score, increased neuronal survival, decreased the levels of serum MDA and brain ROS, increased the levels of serum GSH and SOD. In addition the protein expression levels of RIP1 and RIP3 and the cytokines NF-κB, TNF-α, IL-1β and IL-6 were downregulated compared with the TBI group, which demonstrated that hydrogen-rich saline-induced inhibition of necroptosis and neuroinflammation ameliorated neuronal death following TBI. The neuroprotective capacity of hydrogen-rich saline was demonstrated to be partly dependent on the ROS/heme oxygenase-1 signaling pathway. Taken together, the findings of the present study indicated that hydrogen-rich saline enhanced neurological outcomes in mice and minimized neuronal death by inducing protective effects against neural necroptosis as well as neuroinflammation.

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Exploring the Molecular and Genetic Mechanisms of Action of the α2-Adrenergic Agonist Mafedine in Experimental Traumatic Brain Injury in Rats

Sysoev

Shustov

Prikhodko

et al. 2023

J Evol Biochem Phys

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Dexmedetomidine Inhibits Inflammation to Alleviate Early Neuronal Injury via TLR4/NF-κB Pathway in Rats with Traumatic Brain Injury

Cited by 11 publications

References 0 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

Hydrogen‑rich saline alleviates early brain injury through inhibition of necroptosis and neuroinflammation via the ROS/HO‑1 signaling pathway after traumatic brain injury

Exploring the Molecular and Genetic Mechanisms of Action of the α2-Adrenergic Agonist Mafedine in Experimental Traumatic Brain Injury in Rats

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