Hydrogen inhalation improves mouse neurological outcomes after cerebral ischemia/reperfusion independent of anti-necroptosis

Huang, Jun; Liu, Wenwu; Sun, Xuejun

doi:10.4103/2045-9912.229596

Cited by 18 publications

(8 citation statements)

References 31 publications

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“…In addition, the oxygen concentration was at a higher than normal level in the hydrogen mixture produced by the electrolysis of water. Although our previous study showed 66.7% nitrogen and 33.3% oxygen had no significant influence, the effects of elevated oxygen concentration should be confirmed by investigation (Huang et al, 2018).…”

Section: Discussionmentioning

confidence: 61%

Lung macrophages are involved in lung injury secondary to repetitive diving

Ning¹,

Guan

Lu³

et al. 2020

J. Zhejiang Univ. Sci. B

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This study aimed to establish an animal model of decompression-induced lung injury (DILI) secondary to repetitive diving in mice and explore the role of macrophages in DILI and the protective effects of high-concentration hydrogen (HCH) on DILI. Mice were divided into three groups: control group, DILI group, and HCH group. Mice were exposed to hyperbaric air at 600 kPa for 60 min once daily for consecutive 3 d and then experienced decompression. In HCH group, mice were administered with HCH (66.7% hydrogen and 33.3% oxygen) for 60 min after each hyperbaric exposure. Pulmonary function tests were done 6 h after decompression; the blood was harvested for cell counting; the lung tissues were harvested for the detection of inflammatory cytokines, hematoxylin and eosin (HE) staining, and immunohistochemistry; western blotting and polymerase chain reaction (PCR) were done for the detection of markers for M1 and M2 macrophages. Our results showed that bubbles formed after decompression and repeated hyperbaric exposures significantly reduced the total lung volume and functional residual volume. Moreover, repetitive diving dramatically increased proinflammatory factors and increased the markers of both M1 and M2 macrophages. HCH inhalation improved lung function to a certain extent, and significantly reduced the pro-inflammatory factors. These effects were related to the reduction of M1 macrophages as well as the increase in M2 macrophages. This study indicates that repetitive diving damages lung function and activates lung macrophages, resulting in lung inflammation. HCH inhalation after each diving may be a promising strategy for the prevention of DILI.

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Section: Discussionmentioning

confidence: 61%

Lung macrophages are involved in lung injury secondary to repetitive diving

Ning¹,

Guan

Lu³

et al. 2020

J. Zhejiang Univ. Sci. B

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“…Hydroxyl radicals are the most cytotoxic of ROS; H 2 has a strong ability to eliminate hydroxyl radicals and peroxynitrite [ 22 , 24 ]. Previous researches have demonstrated 67% H 2 and 33% O 2 mixture gas strikingly decreased ROS induced by ischemia-reperfusion in the brain [ 34 , 50 ], liver [ 51 ], and heart [ 52 ] in animal models. Clinical studies have reported 67% H 2 and 33% O 2 mixture reduced the inspiratory effort in patients with acute severe tracheal stenosis [ 53 ] and restored the exhausted supply of CD8+ T cells in patients with advanced colorectal cancer [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Hydrogen and Oxygen Mixture to Improve Cardiac Dysfunction and Myocardial Pathological Changes Induced by Intermittent Hypoxia in Rats

Zhao

Yang

et al. 2019

Oxidative Medicine and Cellular Longevity

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Obstructive sleep apnea (OSA) can cause intermittent changes in blood oxygen saturation, resulting in the generation of many reactive oxygen species (ROS). To discover new antioxidants and clarify the endoplasmic reticulum (ER) stress involved in cardiac injury in OSA, we established a chronic intermittent hypoxia (CIH) rat model with a fraction of inspired O2 (FiO2) ranging from 21% to 9%, 20 times/h for 8 h/day, and the rats were treated with H2-O2 mixture (67% hydrogen and 33% oxygen) for 2 h/day for 35 days. Our results showed that H2-O2 mixture remarkably improved cardiac dysfunction and myocardial fibrosis. We found that H2-O2 mixture inhalation declined ER stress-induced apoptosis via three major response pathways: PERK-eIF2α-ATF4, IRE 1-XBP1, and ATF 6. Furthermore, we revealed that H2-O2 mixture blocked c-Jun N-terminal kinase- (JNK-) MAPK activation, increased the ratio of Bcl-2/Bax, and inhibited caspase 3 cleavage to protect against CIH-induced cardiac apoptosis. In addition, H2-O2 mixture considerably decreased ROS levels via upregulating superoxide dismutase (SOD) and glutathione (GSH) as well as downregulating NADPH oxidase (NOX 2) expression in the hearts of CIH rats. All the results demonstrated that H2-O2 mixture significantly reduced ER stress and apoptosis and that H2 might be an efficient antioxidant against the oxidative stress injury induced by CIH.

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“…Although cell death due to primary HI insult was not preventable, the delayed cell death of both necrosis and apoptosis appeared to be reduced in this study. In one study of a HI mouse model, inhalation of high-concentration H 2 improved the neurological outcome and reduced infarct size and oedema after cerebral ischaemia/reperfusion, even though H 2 acts independently of antinecroptosis pathways 19 .…”

Section: Discussionmentioning

confidence: 99%

Hydrogen ventilation combined with mild hypothermia improves short-term neurological outcomes in a 5-day neonatal hypoxia-ischaemia piglet model

Htun

Nakamura

Nakao

et al. 2019

Sci Rep

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Despite its poor outcomes, therapeutic hypothermia (TH) is the current standard treatment for neonatal hypoxic-ischaemic encephalopathy (HIE). In this study, due to its antioxidant, anti-inflammatory, and antiapoptotic properties, the effectiveness of molecular hydrogen (H2) combined with TH was evaluated by means of neurological and histological assessments. Piglets were divided into three groups: hypoxic-ischaemic insult with normothermia (NT), insult with hypothermia (TH, 33.5 ± 0.5 °C), and insult with hypothermia with H2 ventilation (TH-H2, 2.1–2.7%). H2 ventilation and TH were administered for 24 h. After ventilator weaning, neurological assessment was performed every 6 h for 5 days. On day 5, the brains of the piglets were harvested for histopathological analysis. Regarding the neurological score, the piglets in the TH-H2 group consistently had the highest score from day 2 to 5 and showed a significantly higher neurological score from day 3 compared with the NT group. Most piglets in the TH-H2 group could walk at day 3 of recovery, whereas walking ability was delayed in the two other groups. The histological results revealed that TH-H2 tended to improve the status of cortical gray matter and subcortical white matter, with a considerable reduction in cell death. In this study, the combination of TH and H2 improved short-term neurological outcomes in neonatal hypoxic-ischaemic piglets.

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Hydrogen inhalation improves mouse neurological outcomes after cerebral ischemia/reperfusion independent of anti-necroptosis

Cited by 18 publications

References 31 publications

Lung macrophages are involved in lung injury secondary to repetitive diving

Lung macrophages are involved in lung injury secondary to repetitive diving

Hydrogen and Oxygen Mixture to Improve Cardiac Dysfunction and Myocardial Pathological Changes Induced by Intermittent Hypoxia in Rats

Hydrogen ventilation combined with mild hypothermia improves short-term neurological outcomes in a 5-day neonatal hypoxia-ischaemia piglet model

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