Hydrogen improves cell viability partly through inhibition of autophagy and activation of PI3K/Akt/GSK3β signal pathway in a microvascular endothelial cell model of traumatic brain injury

Wang, Yifeng; Wang, Lu; Hu, Tianpeng; Wang, Feng; Han, Zhaoli; Yin, Zhenyu; Ge, Xintong; Xie, Keliang; Lei, Ping

doi:10.1080/01616412.2020.1747717

Cited by 24 publications

(18 citation statements)

References 41 publications

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“…Hence, studies aiming to further clarify the pathophysiological mechanisms of TBI and search for new and effective pharmacological intervention targets are important and necessary. The pathophysiology of TBI includes several different physiological changes and mainly involves primary brain injury and secondary brain injury, which lead to neuronal death, neurological deficits and mortality following TBI ( 11 ). 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.…”

Section: Introductionmentioning

confidence: 99%

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%

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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“…Moreover, it was found that H 2 downregulated the expression levels of p-JNK1/2 and p-AKT in the vmPFC. Previous studies also suggested that inhibition of JNK1/2 and AKT activations may be involved in the anti-apoptotic ability of H 2 (55,56). Thus, besides JNK1/2 and AKT signaling, inhibition of p38 MAPK signaling is also a plausible mechanism for H 2 -dependent neuroprotection following SAH.…”

Section: Discussionmentioning

confidence: 90%

Hydrogen gas post‑conditioning alleviates cognitive dysfunction and anxiety‑like behavior in a rat model of subarachnoid hemorrhage

et al. 2021

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Subarachnoid hemorrhage (SAH) results in high rates of mortality and lasting disability. Hydrogen gas (H 2 ) is an antioxidant with demonstrated neuroprotective efficacy. The present study examined the therapeutic efficacy of H 2 inhalation on early brain injury following experimental SAH in rats and the potential underlying molecular mechanisms. The rats were randomly separated into three groups (n=36 per group): Sham, SAH and SAH + H 2 . Endovascular perforation of the right internal carotid artery was used to establish SAH. After perforation, rats in the SAH + H 2 group inhaled 2.9% H 2 with regular oxygen for 2 h. Then, 24 h post-SAH, TUNEL staining was used to detect apoptotic neurons, and both immunostaining and western blotting were conducted to examine changes in p38 MAPK activity and the expression levels of apoptotic regulators (Bcl-2, Bax and cleaved caspase-3) in the ventromedial prefrontal cortex. Then, 30 day post-SAH, Nissl staining was performed to detect neuronal injury, brain MRI was conducted to detect gross changes in brain structure and metabolism, the open field test was used to assess anxiety and the novel object recognition test was performed to assess memory. H 2 inhalation following experimental SAH stabilized brain metabolites, improved recognition memory and reduced anxiety-like behavior, the neuronal apoptosis rate, phosphorylated p38 MAPK expression, cleaved caspase-3 expression and the Bax/Bcl-2 ratio. Collectively, the present results suggested that H 2 inhalation can alleviate SAH-induced cognitive impairment, behavioral abnormalities and neuronal apoptosis in rats, possibly via inhibition of the p38 MAPK signal pathway.

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“…Chen 46 reported that H 2 can alleviate vital organ damage, inhibited lipopolysaccharide (LPS) and ATP caused by NLRP3 inflammasome pathway activation, and improve mitochondrial dysfunction via regulating autophagy. Recent studies also indicated that hydrogen-rich saline or hydrogen gas can decrease cell death via regulating autophagy [47][48][49][50] . So far, this is the first report that hydrogen-rich saline can alleviate EBI after SAH by regulating autophagy.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen-rich saline alleviates early brain injury through regulating of ER stress and autophagy after experimental subarachnoid hemorrhage

Jiang

Dai

et al. 2021

Acta Cir. Bras.

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Purpose: Subarachnoid hemorrhage (SAH) is a common complication of cerebral vascular disease. Hydrogen has been reported to alleviate early brain injury (EBI) through oxidative stress injury, reactive oxygen species (ROS), and autophagy. Autophagy is a programmed cell death mechanism that plays a vital role in neuronal cell death after SAH. However, the precise role of autophagy in hydrogen-mediated neuroprotection following SAH has not been confirmed. Methods: In the present study, the objective was to investigate the neuroprotective effects and potential molecular mechanisms of hydrogen-rich saline in SAH-induced EBI by regulating neural autophagy in the C57BL/6 mice model. Mortality, neurological score, brain water content, ROS, malondialdehyde (MDA), and neuronal death were evaluated. Results: The results show that hydrogen-rich saline treatment markedly increased the survival rate and neurological score, increased neuron survival, downregulated the autophagy protein expression of Beclin-1 and LC3, and endoplasmic reticulum (ER) stress. That indicates that hydrogen-rich saline-mediated inhibition of autophagy and ER stress ameliorate neuronal death after SAH. The neuroprotective capacity of hydrogen-rich saline is partly dependent on the ROS/Nrf2/heme oxygenase-1 (HO-1) signaling pathway. Conclusion: The results of this study demonstrate that hydrogen-rich saline improves neurological outcomes in mice and reduces neuronal death by protecting against neural autophagy and ER stress.

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Hydrogen improves cell viability partly through inhibition of autophagy and activation of PI3K/Akt/GSK3β signal pathway in a microvascular endothelial cell model of traumatic brain injury

Cited by 24 publications

References 41 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 gas post‑conditioning alleviates cognitive dysfunction and anxiety‑like behavior in a rat model of subarachnoid hemorrhage

Hydrogen-rich saline alleviates early brain injury through regulating of ER stress and autophagy after experimental subarachnoid hemorrhage

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