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Effects of hyperbaric oxygen on Notch signaling pathway after severe carbon monoxide poisoning in mice.

ABSTRACT: Demyelination of the cerebral white matter is the most common pathological change after carbon monoxide (CO) poisoning. Notch signaling, the mechanism underlying the differentiation of astrocytes and oligodendrocytes, is critical to remyelination of the white matter after brain lesion. The purpose of this work was to determine the effects of hyperbaric oxygen (HBO) on Notch signaling pathway after CO poisoning for the explanation of the protective effects of HBO on CO-poisoning-related cerebral white matter demyelination. The male C57 BL/6 mice with severe CO poisoning were treated by HBO. And HBO therapy shortened the escape latency and improved the body mass after CO poisoning. HBO therapy also significantly suppressed protein and mRNA levels of Notch1 and Hes5 after CO poisoning. Our findings suggested that HBO could suppress the activation of Notch signaling pathway after CO poisoning, which is the mechanism underlying the neuroprotection of HBO on demyelination after severe CO poisoning.

SUBMITTER: Hu HJ

PROVIDER: S-EPMC9480357 | biostudies-literature | 2023 Jan-Mar

REPOSITORIES: biostudies-literature

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Effects of hyperbaric oxygen on Notch signaling pathway after severe carbon monoxide poisoning in mice.

Hu Hui-Jun HJ Fan Dan-Feng DF Ye Zhou-Heng ZH Sun Qiang Q

Medical gas research 20230101 1

Demyelination of the cerebral white matter is the most common pathological change after carbon monoxide (CO) poisoning. Notch signaling, the mechanism underlying the differentiation of astrocytes and oligodendrocytes, is critical to remyelination of the white matter after brain lesion. The purpose of this work was to determine the effects of hyperbaric oxygen (HBO) on Notch signaling pathway after CO poisoning for the explanation of the protective effects of HBO on CO-poisoning-related cerebral ...[more]

PMID: 35946219

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Project description:BACKGROUND:Poisoning with carbon monoxide (CO) remains an important cause of accidental and intentional injury worldwide. Several unblinded non-randomized trials have suggested that the use of hyperbaric oxygen (HBO) prevents the development of neurological sequelae. This has led to the widespread use of HBO in the management of patients with carbon monoxide poisoning. OBJECTIVES:To examine randomised trials of the efficacy of hyperbaric oxygen (HBO) compared to normobaric oxygen (NBO) for the prevention of neurologic sequelae in patients with acute carbon monoxide poisoning. SEARCH STRATEGY:We searched the following electronic databases; Cochrane Injuries Group Specialised Register (searched June 2010), Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 2), MEDLINE (Ovid SP) 1950 to June 2010, EMBASE (Ovid SP) 1980 to June 2010, ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) 1970 to June 2010, ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S) 1990 to June 2010. SELECTION CRITERIA:All randomised controlled trials of HBO compared to NBO, involving non-pregnant adults who are acutely poisoned with carbon monoxide (regardless of severity). DATA COLLECTION AND ANALYSIS:Two authors independently extracted from each trial information on: the number of randomised patients, types of participants, the dose and duration of the intervention, and the prevalence of neurologic symptoms at follow-up. MAIN RESULTS:Seven randomised controlled trials of varying quality were identified; one was excluded because it did not evaluate clinical outcomes. Of the six remaining trials involving 1361 participants, two found a beneficial effect of HBO for the reduction of neurologic sequelae at one month, while four others did not. One of these is an incomplete publication (an abstract of an interim analysis). Although pooled random effects meta-analysis does not suggest a significant benefit from HBOT (OR for neurological deficits 0.78, 95%CI 0.54 to 1.12), significant methodologic and statistical heterogeneity was apparent among the trials, and this result should be interpreted cautiously. Moreover, design or analysis flaws were evident in all trials. Importantly, the conclusions of one positive trial may have been influenced by failure to adjust for multiple hypothesis testing, while interpretation of the other positive trial is hampered by a high risk of bias introduced during the analysis including an apparent change in the primary outcome. Both were also stopped early 'for benefit', which is likely to have inflated the observed effect. In contrast three negative trials had low power to detect a benefit of HBO due to exclusion of severely poisoned patients in two and very poor follow-up in the other. One trial that was said to be finished around eight years ago has not reported the final analysis in any forum. AUTHORS' CONCLUSIONS:Existing randomised trials do not establish whether the administration of HBO to patients with carbon monoxide poisoning reduces the incidence of adverse neurologic outcomes. Additional research is needed to better define the role, if any, of HBO in the treatment of patients with carbon monoxide poisoning. This research question is ideally suited to a multi-center randomised controlled trial.

Project description:BackgroundHyperbaric oxygen therapy (HBO2) is recommended for symptomatic patients within 24 h of carbon monoxide (CO) poisoning. Currently, there is no consensus on the number of HBO2 sessions within 24 h after arrival at the hospital. Therefore, we evaluated differences in the therapeutic effects according to the number of HBO2 sessions in acute CO poisoning.MethodsThis cohort study included data collected from our CO poisoning registry and prospective cohorts between January 2006 and August 2021 in a single academic medical center in South Korea. Based on the number of HBO2 sessions performed within 24 h, we classified patients into one- and multiple- (two or three) session groups. We also compared mild (non-invasive mechanical ventilation) and severe (invasive mechanical ventilation) groups. CO-related neurocognitive outcomes were measured using the Global Deterioration Scale (GDS; stages: 1-7) combined with neurological impairment at 1 month after poisoning. We classified GDS stages as favorable (1-3 stages) and poor (4-7 stages) neurocognitive outcomes. Patients belonging to a favorable group based on GDS assessment, but with observable neurological impairment, were assigned to the poor outcome group. Propensity score matching (PSM) was performed to adjust for age, sex, and related variables to identify statistical differences between groups.ResultsWe analyzed the data of 537 patients between ages 16 and 70 years treated with HBO2. After PSM, there was no significant difference in neurocognitive outcomes at 1 month among the two groups of patients (p = 0.869). Furthermore, there were no significant differences in neurocognitive outcomes between invasive mechanical ventilation and non-invasive mechanical ventilation patients in the three groups (p = 0.389 and p = 0.295).ConclusionThere were no significant differences in the reduction of poor neurocognitive outcomes according to the number of HBO2 sessions implemented within 24 h of CO exposure.

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Effects of hyperbaric oxygen on Notch signaling pathway after severe carbon monoxide poisoning in mice.

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Effects of hyperbaric oxygen on Notch signaling pathway after severe carbon monoxide poisoning in mice.

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