Stroke, which is defined as a neurologic deficit caused by sudden impaired blood supply, has been considered as a common cause of death and disability for decades. The World Health Organization has declared that almost every 5 seconds a new stroke occurs, placing immense socioeconomic burdens. However, the effective and available treatment strategies are still limited. Additionally, the most effective therapy, such as thrombolysis and stenting for ischemic stroke, generally requires a narrow therapeutic time window after the event. A large majority of patients cannot be admitted to hospital and receive these effective treatments for reperfusion timely. Hyperbaric oxygen therapy (HBOT) has been frequently applied and investigated in stroke since 1960s. Numerous basic and clinical studies have shown the beneficial efficacy for neurological outcome after stroke, and meanwhile many underlying mechanisms associated with neuroprotection have been illustrated, such as cerebral oxygenation promotion and metabolic improvement, blood-brain barrier protection, anti-inflammation and cerebral edema, intracranial pressure modulation, decreased oxidative-stress and apoptosis, increased vascular and neural regeneration. However, HBOT in human stroke is still not sufficiently evidence-based, due to the insufficient randomized double-blind controlled clinical studies. To date, there are no uniform criteria for the dose and session duration of HBOT in different strokes. Furthermore, the additional effect of HBOT combined with drugs and other treatment strategies are being investigated recently. Therefore, more experimental and clinical research is imperative to identify the mechanisms more clearly and to explore the best protocol of HBOT in stroke treatment.

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Traumatic brain injury (TBI) is a serious public health problem in the United States. Survivors of TBI are often left with significant cognitive, behavioral, and communicative disabilities. So far there is no effective treatment/intervention in the daily clinical practice for TBI patients. The protective effects of hyperbaric oxygen therapy (HBOT) have been proved in stroke; however, its efficiency in TBI remains controversial. In this review, we will summarize the results of HBOT in experimental and clinical TBI, elaborate the mechanisms, and bring out our current understanding and opinions for future studies.

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Stroke is a kind of acute cerebrovascular disease characterized by the focal lack of neurological function, including ischemic stroke and hemorrhagic stroke. As society ages rapidly, stroke has become the second leading cause of disability and death, and also become the main threat to human health and life. In recent years, findings from increasing animal and clinical trials have supplied scientific evidences for the treatment of stroke. Hydrogen sulfide (H ₂ S), which has always been seen as a toxic gas, now has been thought to be the third gaseous signaling molecule following nitric oxide and carbon monoxide. Accumulating evidences indicate that H ₂ S plays an important role in stroke. Given that its neuroprotective effect is dose-dependent, only when its concentration is relatively low, H ₂ S can yield the neuroprotection, while high dose may lead to neurotoxicity. All these study results suggest that H ₂ S may offer a new promising application for the therapy of stroke. Here, our review will present the role of H ₂ S in stroke from its mechanism to animal and clinical studies.

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Recent data have shown that normobaric oxygen (NBO) increases the catalytic and thrombolytic efficiency of recombinant tissue plasminogen activator (rtPA) in vitro, and is as efficient as rtPA at restoring cerebral blood flow in rats subjected to thromboembolic brain ischemia. Therefore, in the present study, we studied the effects of hyperbaric oxygen (HBO) (i) on rtPA-induced thrombolysis in vitro and (ii) in rats subjected to thromboembolic middle cerebral artery occlusion-induced brain ischemia. HBO increases rtPA-induced thrombolysis in vitro to a greater extent than NBO; in addition, HBO treatment of 5-minute duration, but not of 25-minute duration, reduces brain damage and edema in vivo. In line with the facilitating effect of NBO on cerebral blood flow, our findings suggest that 5-minute HBO could have provided neuroprotection by promoting thrombolysis. The lack of effect of HBO exposure of longer duration is discussed.

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Postoperative nausea and vomiting (PONV) is a common complication after general anesthesia. Recent studies suggested that the hippocampus is involved in PONV. Hypothesising that hippocampal dopaminergic neurons are related to PONV, we examined the comprehensive mRNA profile of the hippocampus, using a sevoflurane-treated mouse model to confirm this. This study was conducted after approval from our institutional animal ethics committee, the Animal Research Center of Sapporo Medical University School of Medicine (project number: 12-033). Eight mice were assigned to two groups: a naοve group and a sevoflurane group (Sev group). In the Sev group, four mice were anesthetised with 3.5% sevoflurane for 1 hour. Subsequently, mRNA was isolated from their hippocampal cells and RNA sequencing was performed on an Illumina HiSeq 2500 platform. Mapping of the quality-controlled, filtered paired-end reads to mouse genomes and quantification of the expression levels of each gene were performed using R software. The Rtn4rl2 gene that encodes the Nogo receptor was the most up-regulated gene in the present study. The expression levels of dopamine receptor genes and the tachykinin gene were increased by sevoflurane exposure, while the genes related to serotonin receptors were not altered by sevoflurane exposure. The expression levels of LIM-homeodomain-related genes were highly down-regulated by sevoflurane. These findings suggest that sevoflurane exposure induces dopaminergic stimulation of hippocampal neurons and triggers PONV, while neuronal inflammation caused by LIM-homeodomain-related genes is down-regulated by sevoflurane.

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Numerous studies have confirmed the role of endogenous carbon monoxide (CO) gas as a signal transmitter. However, CO is considered an intracellular transmitter, as no studies have demonstrated the redistribution of CO from the blood to tissue cells. Tracer analyses of ¹³ CO ₂ production following ¹³ CO gas inhalation demonstrated that CO is oxidized to carbon dioxide (CO ₂ ) in the body and that CO oxidation does not occur in the circulation. However, these results could not clearly demonstrate the redistribution of CO, because oxidation may have occurred in the airway epithelium. The objective of this study, therefore, was to definitively demonstrate and quantify the redistribution and oxidation of CO using time-course analyses of CO and ¹³ CO ₂ production following ¹³ CO-hemoglobin infusion. The subject was infused with 0.45 L of ¹³ CO-saturated autologous blood. Exhaled gas was collected intermittently for 36 hours for measurement of minute volumes of CO/CO ₂ exhalation and determination of the ¹³ CO ₂ / ¹² CO ₂ ratio. ¹³ CO ₂ production significantly increased from 3 to 28 hours, peaking at 8 hours. Of the infused CO, 81% was exhaled as CO and 2.6% as ¹³ CO ₂ . Identical time courses of ¹³ CO ₂ production following ¹³ CO-hemoglobin infusion and ¹³ CO inhalation refute the hypothesis that CO is oxidized in the airway epithelium and clearly demonstrate the redistribution of CO from the blood to the tissues. Quantitative analyses have revealed that 19% of CO in the circulating blood is redistributed to tissue cells, whereas 2.6% is oxidized there. Overall, these results suggest that CO functions as a systemic signal transmitter.

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Hyperoxic acute lung injury (HALI) refers to the damage to the lungs secondary to exposure to elevated oxygen partial pressure. HALI has been a concern in clinical practice with the development of deep diving and the use of normobaric as well as hyperbaric oxygen in clinical practice. Although the pathogenesis of HALI has been extensively studied, the findings are still controversial. Nitric oxide (NO) is an intercellular messenger and has been considered as a signaling molecule involved in many physiological and pathological processes. Although the role of NO in the occurrence and development of pulmonary diseases including HALI has been extensively studied, the findings on the role of NO in HALI are conflicting. Moreover, inhalation of NO has been approved as a therapeutic strategy for several diseases. In this paper, we briefly summarize the role of NO in the pathogenesis of HALI and the therapeutic potential of inhaled NO in HALI.

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Carbon monoxide (CO) has long been considered an environmental pollutant and a poison. Exogenous exposure to amounts of CO beyond the physiologic level of the body can result in a protective or adaptive response. However, as a gasotransmitter, endogenous CO is important for multiple physiologic functions. To date, at least seven distinct methods of delivering CO have been utilized in animal and clinical studies. In this mini-review, we summarize the exogenous CO delivery methods and compare their advantages and disadvantages.

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The occurrence of paroxysmal narcotic episodes including psychotic-like symptoms in divers participating to experimental deep diving programs with various gas mixtures has constituted, beyond the classical symptoms of the high-pressure neurological syndrome, the major limitation for deep diving. With the development of new saturation deep diving programs and experiments by the eastern nations, such as India and China, we believed that it is of interest to examine what could be the ultimate depth that could be reached by saturation human divers. Based on previous data and the critical volume model of inert gas narcosis, we propose that the ultimate depth for saturation diving could be around 1,000 m.

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