Effect of Hyperbaric oxygen on myelin injury and repair after hypoxic-ischemic brain damage in adult rat.

INTRODUCTION: Hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of death and neurological disability with limited options for treatment in neonates, children and adults worldwide. The pathogenesis and treatment of white matter (WM) injury in adult patients with HIE remains largely elusive. METHODS: Sixty male Sprague-Dawley rats were randomly divided into control group, sham-operated group (HBO treatment 6 days after sham operation), and Hypoxia-ischemia (HI) induced brain damage group (receiving left carotid arteries ligation + hypoxia treatment), 1.5ATA hyperbaric oxygen group (HI + 1.5ATA HBOT) and 2.5ATA HBOT group (HI + 2.5ATA HBOT). All the rats were evaluated by water maze before operation, and 6 days after operation, and the function of learning and memory was evaluated; Demyelination in the hippocampus and prefrontal cortex was observed by Luxol fast blue staining (LFB) and MBP immunostaining; the number of Myelin Oligodendrocyte Glycoprotein (MOG),glial fibrillary acidic protein (GFAP), ionic calcium-binding adaptor (Iba-1) and NG2 positive cells in the hippocampus and prefrontal cortex were determined by immunofluorescence staining. The expression of interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor (TNF-α), Hypoxia Inducible Factor 1 Subunit Alpha (HIF1-α) and Superoxide dismutase (SOD) in brain and serum of rats were measured by Western Blot method and Enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with those in the normal control group and sham-operated group, in the HI group, the learning and memory abilities of rats were significantly decreased (P < 0.05), the intensity of LFB and MBP immunostaining in hippocampus and prefrontal cortex was significantly decreased (P < 0.05); the number of MOG positive oligodendrocytes (OLs) significantly decreased (P < 0.05), whereas the number of Iba-1, GFAP, NG2 positive microglias, astrocytes and oligodendrocyte precursors (OPCs) was increased (P < 0.05); the level of IL-1ß, IL-6, TNF-α and HIF-1a in brain and serum were significantly increased (P < 0.05), whereas SOD was significantly decreased in brain and increased in serum. Compared with those in the HI group, in both 1.5ATA and 2.5ATA HBOT group, the learning and memory abilities were significantly increased (P < 0.05); the intensity of LFB and MBP immunostaining in the hippocampus and prefrontal cortex was significantly increased (P < 0.05); the number of MOG positive OLs significantly increased (P < 0.05); the number of Iba-1, GFAP, NG2 positive microglias, astrocytes and OPCs was decreased (P < 0.05); the level of IL-1ß, IL-6, TNF-α and HIF-1a in brain and serum were significantly decreased (P < 0.05); the level of SOD was significantly increased in brain and decreased in serum. Morever, compared with those in the 1.5ATA group, 2.5ATA provided better treatment results (P < 0.05). CONCLUSION: In the present study, we demonstrated the mechanism of different pressure HBOT on HI induced brain injury from three levels: (1) On a tissue level, HBOT protects against HI induced myelin injury; (2) On a cellular level, HBOT attenuates HI-induced OL loss, suppresss the reactive activation of astrocyte and microglia, and may promote OPC to differentiate into OL; (3) On a molecular level, HBOT inhibites neuroinflammation, and balances oxidative damage and antioxidant capacity. Among the above effects, 2.5ATA HBOT is better than 1.5ATA HBOT. Ongoing research will continue to seek out the signalling pathways and molecules mechanisms on different pressure of HBOT-related myelin protection, and possibly expand suitable HBOT use in adult HIE clinically.

Effects of hyperbaric oxygen on NLRP3 inflammasome activation in the brain after carbon monoxide poisoning.

Neuroinflammation plays an important role in brain damage after acute carbon monoxide poisoning (ACOP). The nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing (NLRP) 3 inflammasome triggers the activation of inflammatory caspases and maturation of interleukin (IL)-1ß and -18, and has been linked to various human autoinflammatory and autoimmune diseases. In this study we investigated the effects of hyperbaric oxygen (HBO2) on NLRP3 inflammasome activation after ACOP. Mice were randomly divided into four groups: sham group (exposure to normobaric air - i.e., 21% O2 at 1 atmosphere absolute); HBO2-only group; CO + normobaric air group; and CO + HBO2 group. Cognitive function was evaluated with the Morris water maze; myelin injury was assessed by FluoroMyelin GreenTM fluorescent myelin staining and myelin basic protein (MBP) immunostaining; and mRNA and protein levels of NLRP3 inflammasome complex proteins were measured by quantitative real-time PCR and Western blot, respectively. Additionally, serum and brain levels of IL-1ßß and -18 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase were determined by enzyme-linked immunosorbent assay. It was found that HBO2 improved learning and memory, and alleviated myelin injury in mice subjected to acute CO exposure. Furthermore, HBO2 decreased NLRP3, absent in melanoma 2 (AIM2), caspase-1, and apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain mRNA and protein levels, and reduced brain and serum concentrations of IL-1ß and -18 and NADPH oxidase. These results indicate that HBO2 suppresses the inflammatory response after ACOP by blocking NLRP3 inflammasome activation, thereby alleviating cognitive deficits.

Hyperbaric oxygen therapy may be effective to improve hypoxemia in patients with severe COVID-2019 pneumonia: two case reports.

Objectives: To determine whether hyperbaric oxygen (HBO2) therapy be effective to improve hypoxemia for severe COVID-19 pneumonia patients. Methods: Two male patients ages 57 and 64 years old were treated. Each met at least one of the following criteria: shortness of breath; respiratory rate (RR) ≥30 breaths/minute; finger pulse oxygen saturation (SpO2) ≤93% at rest; and oxygen index (P/F ratio: PaO2/FiO2 ≤300 mmHg). Each case excluded any combination with pneumothorax, pulmonary bullae or other absolute contraindications to HBO2. Patients were treated with 1.5 atmospheres absolute HBO2 with an oxygen concentration of more than 95% for 60 minutes per treatment, once a day for one week. Patients' self-reported symptoms, daily mean SpO2 (SO2), arterial blood gas analysis, D-dimer, lymphocyte, cholinesterase (che) and chest CT were conducted and measured. Results: For both patients, dyspnea and shortness of breath were immediately alleviated after the first HBO2 treatment and remarkably relieved after seven days of HBO2 therapy. The RR also decreased daily. Neither patient became critically ill. The decreasing trend of SO2 and P/F ratio was immediately reversed and increased day by day. The lymphocyte count and ratio corresponding to immune function gradually recovered. D-dimer corresponding to peripheral circulation disorders and serum cholinesterase, reflecting liver function had improved. Follow-up chest CT showed that the pulmonary inflammation had clearly subsided. Conclusion: Our preliminary uncontrolled case reports suggest that HBO2 therapy may promptly improve the progressive hypoxemia of patients with COVID-2019 pneumonia. However, the limited sample size and study design preclude a definitive statement about the potential effectiveness of HBO2 therapy to COVID-2019 pneumonia. It requires evaluation in randomized clinical trials in future.

Hyperbaric Oxygen Alleviates Secondary Brain Injury After Trauma Through Inhibition of TLR4/NF-κB Signaling Pathway.

BACKGROUND: The aim of this study was to investigate the efficacy of hyperbaric oxygen in secondary brain injury after trauma and its mechanism in a rat model. MATERIAL/METHODS: A rat model of TBI was constructed using the modified Feeney's free-fall method, and 60 SD rats were randomly divided into three groups--the sham group, the untreated traumatic brain injury (TBI) group, and the hyperbaric oxygen-treated TBI group. The neurological function of the rats was evaluated 12 and 24 hours after TBI modeling; the expression levels of TLR4, IκB, p65, and cleaved caspase-3 in the peri-trauma cortex were determined by Western blot; levels of TNF-α, IL-6, and IL-1ß were determined by ELISA; and apoptosis of the neurons was evaluated by TUNEL assay 24 hours after TBI modeling. RESULTS: Hyperbaric oxygen therapy significantly inhibited the activation of the TLR4/NF-κB signaling pathway, reduced the expression of cleaved caspase-3, TNF-α, IL-6 and IL-1ß (P<0.05), reduced apoptosis of the neurons and improved the neurological function of the rats (P<0.05). CONCLUSIONS: Hyperbaric oxygen therapy protects the neurons after traumatic injury, possibly through inhibition of the TLR4/NF-κB signaling pathway.