Hyperbaric Oxygen Pretreatment Research Articles

Hyperbaric Oxygen Reduces Oxidative Stress Impairment and DNA Damage and Simultaneously Increases HIF-1α in Ischemia-Reperfusion Acute Kidney Injury.

The central exacerbating factor in the pathophysiology of ischemic-reperfusion acute kidney injury (AKI) is oxidative stress. Lipid peroxidation and DNA damage in ischemia are accompanied by the formation of 3-nitrotyrosine, a biomarker for oxidative damage. DNA double-strand breaks (DSBs) may also be a result of postischemic AKI. γH2AX(S139) histone has been identified as a potentially useful biomarker of DNA DSBs. On the other hand, hypoxia-inducible factor (HIF) is the "master switch" for hypoxic adaptation in cells and tissues. The aim of this research was to evaluate the influence of hyperbaric oxygen (HBO) preconditioning on antioxidant capacity estimated by FRAP (ferric reducing antioxidant power) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assay, as well as on oxidative stress parameter 3-nitrotyrosine, and to assess its effects on γH2AX(S139), HIF-1α, and nuclear factor-κB (NF-κB) expression, in an experimental model of postischemic AKI induced in spontaneously hypertensive rats. The animals were divided randomly into three experimental groups: sham-operated rats (SHAM, n = 6), rats with induced postischemic AKI (AKI, n = 6), and group exposed to HBO preconditioning before AKI induction (AKI + HBO, n = 6). A significant improvement in the estimated glomerular filtration rate, eGFR, in AKI + HBO group (p < 0.05 vs. AKI group) was accompanied with a significant increase in plasma antioxidant capacity estimated by FRAP (p < 0.05 vs. SHAM group) and a reduced immunohistochemical expression of 3-nitrotyrosine and γH2AX(S139). Also, HBO pretreatment significantly increased HIF-1α expression (p < 0.001 vs. AKI group), estimated by Western blot and immunohistochemical analysis in kidney tissue, and decreased immunohistochemical NF-κB renal expression (p < 0.01). Taking all of these results together, we may conclude that HBO preconditioning has beneficial effects on acute kidney injury induced in spontaneously hypertensive rats.

Hyperbaric oxygen therapy does not alleviate tourniquet-induced acute ischemia-reperfusion injury in mouse skeletal muscles

During tourniquet application, blood flow is restricted to a limb to stop excessive limb hemorrhage in a trauma setting and to create a bloodless operating field in the surgical setting. During tourniquet-related ischemia, aerobic respiration stops, and ATP is depleted, and during subsequent reperfusion, there is an increase in reactive oxygen species (ROS) production and other endogenous substances, which leads to acute ischemia-reperfusion (IR) injuries, including tissue necrosis and skeletal muscle contractile dysfunction. Hyperbaric oxygen (HBO) therapy can increase the arterial oxygen tension in the tissues of patients with general hypoxia/anoxia, including carbon monoxide poisoning, circulatory arrest, and cerebral and myocardial ischemia. Here, we studied the protective effects of HBO pretreatment with 100% oxygen at 2.5 ATA against tourniquet/IR injury in mice. After one hour of HBO therapy with 100% oxygen at 2.5 ATA was administered to C57/BL6 mice, a rubber band was placed at the hip joint of the unilateral hindlimb to induce 3 h of ischemia and then released for 48 h of reperfusion. We analyzed gastrocnemius muscle morphology and contractile function and measured the levels of ATP and ROS accumulation in the muscles. HBO pretreatment did not improve tourniquet/IR-injured gastrocnemius muscle morphology and muscle contraction. Tourniquet/IR mice with HBO pretreatment showed no increase in ATP levels in IR tissues, but they did have a decreased amount of ROS accumulation in the muscles, compared to IR mice with no HBO pretreatment. These data suggest that one hour of HBO pretreatment with 100% oxygen at 2.5 ATA increases the antioxidant response to lower ROS accumulation but does not increase ATP levels in IR muscles and improve tourniquet/IR-injured muscle morphology and contractile function.

MEK1/2 Inhibition Synergistically Enhances the Preventive Effects of Normobaric Oxygen on Spinal Cord Injury in Decompression Sickness Rats

A previous study from our team found that hyperbaric oxygen (HBO) pretreatment attenuated decompression sickness (DCS) spinal cord injury by upregulating heat shock protein 32 (HSP32) via the ROS/p38 MAPK pathway. Meanwhile, a MEK1/2-negative regulatory pathway was also activated to inhibit HSP32 overexpression. The purpose of this study was to determine if normobaric oxygen (NBO) might effectively induce HSP32 while concurrently inhibiting MEK1/2 and to observe any protective effects on spinal cord injury in DCS rats. The expression of HSP32 in spinal cord tissue was measured at 6, 12, 18, and 24 h following NBO and MEK1/2 inhibitor U0126 pretreatment. The peak time of HSP32 was observed at 12 h after simulated air diving. Subsequently, signs of DCS, hindlimb motor function, and spinal cord and serum injury biomarkers were recorded. NBO-U0126 pretreatment significantly decreased the incidence of DCS, improved motor function, and attenuated oxidative stress, inflammatory response, and apoptosis in both the spinal cord and serum. These results suggest that pretreatment with NBO and U0126 combined can effectively alleviate DCS spinal cord injury in rats by upregulating HSP32. This may lead to a more convenient approach for DCS injury control, using non-pressurized NBO instead of HBO.

Does hyperbaric oxygen pretreatment with 100% oxygen attenuate tourniquet‐induced acute ischemia‐reperfusion injury in mouse hindlimb?

Tourniquet-induced ischemia-reperfusion (IR) leads to an increase in reactive oxygen species (ROS) production and tissue necrosis and apoptosis during reperfusion, which disrupts the recovery of skeletal muscle contraction. Hyperbaric oxygen (HBO) therapy exposes patients to high oxygen levels at an increased pressure, which increases the amount of ROS in tissues. Using HBO therapy as a pretreatment can promote ischemic tolerance by increasing antioxidant effects in these tissues before the IR injury. In this study, we observed the effects of HBO pretreatment with 100% oxygen at 2.5 ATA on tourniquet-induced IR injury in mice. C57/BL6 mice were treated with 100% oxygen for 60 minutes at 2.5 ATA in a HBO chamber. A rubber band was placed at the hip joint of the unilateral hindlimb of the mice to induce ischemia for 3 hours, which was followed by rubber band release and subsequent reperfusion for 48 hours. All staining and measurements were performed after the 48 hours of reperfusion. TTC staining of the gastrocnemius muscle showed no significant change in IR-induced infarct size after HBO pretreatment. ROS level was decreased in the gastrocnemius muscle of HBO-pretreated IR mice compared to non-HBO-pretreated IR mice. IR mice pretreated with HBO showed a decrease in ATP level in the gastrocnemius muscle compared to mice without HBO treatment. The data suggest that one hour HBO pretreatment with 100% oxygen at 2.5 ATA increases oxidative metabolism but does not decrease tissue necrosis in mice with tourniquet-induced IR injury.

Effects of hyperbaric oxygen pretreatment on brain antioxidant capacity in rats with decompression sickness

Objective: Decompression sickness (DCS) causes serious brain hypoxic-ischemic injury. This experiment was designed to observe whether hyperbaric oxygen (HBO2) pretreatment played a neuroprotective effect in decompression sickness rat models and to explore the mechanism of protective effects. Methods: Sprague-Dawley (SD) male rats were pretreated with HBO2 and then underwent decompression to establish the DCS rat model. Antioxidant capacities were evaluated by detecting peroxides (GPx), superoxide dismutase (SOD), catalase (CAT) activity and malondialdehyde (MDA) content in brains. The levels of metal elements manganese (Mn), zinc (Zn), iron (Fe) and magnesium (Mg) in brain tissues were assessed by flame atomic absorption spectrometry. Necrosis and apoptosis of neurons were assessed by H-E staining and immunohistochemical staining. Results: HBO2 pretreatment reduced the degree of necrosis and apoptosis in brain tissues of decompression sickness rat models. In addition, HBO2 pretreatment increased GPx, SOD and CAT activities and reduced MDA accumulation. It also increased the content of Mn, Zn, Fe and Mg in brain tissue, which are all related to free radical metabolism. Conclusion: These results suggested that HBO2 pretreatment has protective effects on brain injury of rats with decompression sickness. The mechanism of the protective effects may be related to reducing oxidative damage by affecting metal elements in vivo.

Therapeutic effects of hyperbaric oxygen: integrated review.

Hyperbaric oxygen therapy refers to inhalation of pure oxygen in a closed chamber. Hyperbaric oxygen has a therapeutic effect in numerous pathological conditions, such as decompression sickness, arterial gas embolism, carbon monoxide poisoning and smoke inhalation, osteomylitis, osteoradionecrosis and wound healing. Hyperbaric oxygen therapy is used for treating underlying hypoxia. This review indicates the action of hyperbaric oxygen on biochemical and various physiological changes in cellular level. Narrative review covers the current indications and contraindications of hyperbaric oxygen therapy. The review also focuses on the therapeutic effects of hyperbaric oxygen pretreatment and precondition in different pathological conditions. The complications and side effects of hyperbaric oxygen therapy are discussed.

Hyperbaric oxygen protects against myocardial ischemia‑reperfusion injury through inhibiting mitochondria dysfunction and autophagy.

Our previous study demonstrated that hyperbaric oxygen (HBO) improves heart function predominantly through reducing oxygen stress, modulating energy metabolism and inhibiting cell apoptosis. The present study aimed to investigate the protective effects of HBO on mitochondrial function and autophagy using rats with a ligated left anterior descending artery. The cardioprotective effects of HBO were mainly evaluated using ELISA, fluorescent probes, transmission electron microscopy and reverse transcription-quantitative PCR (RT-qPCR). HBO pretreatment for 14 days (once a day) using a 0.25 MPa chamber improved mitochondrial morphology and decreased the number of autophagic vesicles, as observed using a transmission electron microscope. HBO pretreatment significantly increased the levels of ATP, ADP, energy charge and the opening of the mitochondrial permeability transition pore, but decreased the levels of AMP, cytochrome c and reactive oxygen species. Moreover, HBO pretreatment significantly increased the gene or protein expression levels of eIF4E-binding protein 1, mammalian target of rapamycin (mTOR), mitochondrial DNA, NADH dehydrogenase subunit 1, mitofusin 1 and mitofusin 2, whereas it decreased the gene or protein expression levels of autophagy-related 5 (Atg5), cytochrome c, dynamin-related protein 1 and p53, as determined using RT-qPCR or immunohistochemistry. In conclusion, HBO treatment was observed to protect cardiomyocytes during myocardial ischemia-reperfusion injury (MIRI) by preventing mitochondrial dysfunction and inhibiting autophagy. Thus, these results provide novel evidence to support the use of HBO as a potential agent for the mitigation of MIRI.

Benefits of hyperbaric oxygen pretreatment for decompression sickness in Bama pigs.

Decompression sickness (DCS) occurs when ambient pressure is severely reduced during diving and aviation. Hyperbaric oxygen (HBO) pretreatment has been shown to exert beneficial effects on DCS in rats via heat-shock proteins (HSPs). We hypothesized that HBO pretreatment will also reduce DCS via HSPs in swine models. In the first part of our investigation, six swine were subjected to a session of HBO treatment. HSP32, 60, 70 and 90 were detected, before and at 6, 12, 18, 24 and 30 h following exposure in lymphocytes. In the second part of our investigation, another 10 swine were randomly assigned into two groups (five per group). All swine were subjected to two simulated air dives in a hyperbaric chamber with an interval of 7 days. Eighteen hours before each dive, the swine were pretreated with HBO or air: the first group received air pretreatment prior to the first dive and HBO pretreatment prior to the second; the second group were pretreated with HBO first and then air. Bubble loads, skin lesions, inflammation and endothelial markers were detected after each dive. In lymphocytes, all HSPs increased significantly (P<0.05), with the greatest expression appearing at 18 h for HSP32 and 70. HBO pretreatment significantly reduced all the determined changes compared with air pretreatment. The results demonstrate that a single exposure to HBO 18 h prior to diving effectively protects against DCS in the swine model, possibly via induction of HSPs.

Hyperbaric Oxygen Pretreatment Improves Cognition and Reduces Hippocampal Damage Via p38 Mitogen-Activated Protein Kinase in a Rat Model.

PurposeTo investigate the effects of hyperbaric oxygen (HBO) pretreatment on cognitive decline and neuronal damage in an Alzheimer’s disease (AD) rat model.Materials and MethodsRats were divided into three groups: normal saline (NS), AD, and HBO+AD. In the AD group, amyloid β peptide (Aβ)1-40 was injected into the hippocampal CA1 region of the brain. NS rats received NS injection. In the HBO+AD group, rats received 5 days of daily HBO therapy following Aβ1-40 injection. Learning and memory capabilities were examined using the Morris water maze task. Neuronal damage and astrocyte activation were evaluated by hematoxylin-eosin staining and immunohistochemistry, respectively. Dendritic spine density was determined by Golgi-Cox staining. Tumor necrosis factor-α, interleukin-1β, and interleukin-10 production was assessed by enzyme-linked immunosorbent assay. Neuron apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Protein expression was examined by western blotting.ResultsLearning and memory dysfunction was ameliorated in the HBO+AD group, as shown by significantly lower swimming distances and escape latency, compared to the AD group. Lower rates of neuronal damage, astrocyte activation, dendritic spine loss, and hippocampal neuron apoptosis were seen in the HBO+AD than in the AD group. A lower rate of hippocampal p38 mitogen-activated protein kinase (MAPK) phosphorylation was observed in the HBO+AD than in the AD group.ConclusionHBO pretreatment improves cognition and reduces hippocampal damage via p38 MAPK in AD rats.

Cardioprotective Effects of Combined Therapy with Hyperbaric Oxygen and Diltiazem Pretreatment on Myocardial Ischemia-Reperfusion Injury in Rats

Background/Aims: In this study, we examined whether the combination of hyperbaric oxygen (HBO) and diltiazem therapy provided a cardioprotective effect on myocardial ischemia-reperfusion injury (MIRI) rat model. Methods: Sixty healthy Sprague-Dawley rats were randomly divided into sham, IR, diltiazem (5 mg/kg), HBO (0.25 MPa, 60 min) and combination therapy (HBO plus diltiazem) groups. MIRI model was established by ligating the left anterior descending for 30 min, followed by 60 min of reperfusion. Results: The results show that HBO and diltiazem preconditioning significantly improves cardiac function and myocardial infarction area, increases nitric oxide, endothelial nitric oxide synthase and ATPase (Na+-K+-ATPase and Ca2+-Mg2+-ATPase) activity and decreases levels of oxygen stress, myocardial enzymes and endothelin-1. Notably, HBO and diltiazem preconditioning significantly increased Bcl-2 protein expression and decreased Bax protein and caspase-3 mRNA expression. Conclusions: These data indicate that combination therapy protected against heart MIRI by reducing oxygen stress damage, correcting energy metabolism, improving endothelial function and inhibiting cell apoptosis.

Hyperbaric oxygen enhances neutrophil apoptosis and their clearance by monocyte-derived macrophages.

Neutrophil apoptosis and clearance by macrophages are essential for wound healing. Evidence suggests that hyperbaric oxygen (HBO) exposure may enhance neutrophil apoptosis, but HBO effects leading to neutrophil clearance by macrophages are still unclear. In the current study, bovine neutrophils and monocyte-derived macrophages (MDMΦ) were co-cultured under HBO (97.9% O2, 2.1% CO2 at 2.4 atm absolute (ATA)) (1 atm = 101.325 kPa), hyperbaric normoxia (8.8% O2 at 2.4 ATA), normobaric hyperoxia (95% O2, 5% CO2), normoxia (air), and normobaric hypoxia (5% O2, 5% CO2). Phagocytosis of fresh and 22 h aged neutrophils by MDMΦ was increased after HBO pre-treatment, assessed using flow cytometry and light microscopy. Enhanced clearance of neutrophils was accompanied by an increase in H2O2 levels following HBO pre-treatment with upregulation of IL-10 (anti-inflammatory cytokine) mRNA expression in LPS-stimulated MDMΦ that had ingested aged neutrophils. TNF-α (pro-inflammatory cytokine) gene expression did not change in LPS-stimulated MDMΦ that had ingested fresh or aged neutrophils after HBO, pressure, and hyperoxia. These findings suggest that HBO-activated MDMΦ participate in the clearance of apoptotic cells. Uptake of neutrophils by MDMΦ exposed to HBO may contribute to resolution of inflammation, because HBO induced up-regulation of IL-10 mRNA expression.

Effects of hyperbaric oxygen treatment on antimicrobial function and apoptosis of differentiated HL-60 (neutrophil-like) cells

AimsNeutrophil apoptosis is important in the resolution of inflammation in chronic wounds. Hyperbaric oxygen (HBO) therapy, an intermittent inhalation of 100% oxygen at greater than atmospheric pressure, appears to be an effective treatment for chronic wounds. The aim was to use HL-60 cells differentiated using all-trans retinoic acid (ATRA) (neutrophil-like cells) to test the hypothesis that an HBO-induced increase in antimicrobial activity might lead to an increase in apoptosis, thereby contributing to neutrophil clearance from chronic wounds. Main methodsATRA differentiated HL-60 cells, an in vitro neutrophil model, were used to test the effects of normoxia, hypoxia (5% O2), hyperoxia (95% O2), hyperbaric normoxia (pressure) (8.8% O2 at 2.4 ATA) and HBO (97.9% O2 at 2.4 ATA) on antimicrobial function [NBT staining, superoxide and H2O2 production, and phagocytosis activity] and apoptosis (caspase 3/7 activity and morphological changes observed using SYBR Safe staining). Key findingsA single 90min HBO exposure caused an increase in the respiratory burst activity of neutrophil-like cells post exposure. Phagocytosis of Staphylococcus aureus was also increased. HBO pre-treatment had a pro-apoptotic effect, increasing caspase 3/7 activity and causing morphological changes associated with apoptosis. SignificanceThe potential detrimental effect of enhanced antimicrobial activity induced by HBO may be offset by enhanced apoptosis. Both hyperoxia and pressure alone seemed to contribute to the HBO-induced increases in antimicrobial activity and apoptosis, although there was no consistent pattern. These data contribute to explaining the effectiveness of HBO in the treatment of chronic wounds.

Hyperbaric oxygen and cancer: more complex than we expected

Hyperbaric oxygen (HBO) therapy refers to the breathing ofpure oxygen while in a sealed chamber that has been pres-surized at 1.5 to 3 times normal atmospheric pressure. Todate, HBO therapy has been applied in a series of diseaseswith potential hypoxia including decompression sickness,carbonmonoxidepoisoning,gasgangrene,osteomyelitis,andso on (http://en.wikipedia.org/wiki/Hyperbaric_medicine).However, cancer is not an indication for hyperbaric oxygenin both USA and China.Recently, Moen and Stuhr reviewed the evidence on theinfluence of HBO on cancers in past 9 years [1]. Their con-clusionwasconsistentwithtwoprevioussystemicreviewsonHBO and cancer that the use of HBO in patients with malig-nanciesisconsideredsafe.Inthisreview,theysummarizedtherelationship between hypoxia and cancer and the influence ofHBO on cell survival, angiogenesis, metastasis, chemothera-py,andradiotherapy.Finally,theyreviewedtheeffectofHBOon cancer cells of different types. Although they proposedsome explanations on the effects of HBO on cancers, themechanisms are more complex than we expected.HBO, hypoxia, and angiogenesisIt has been accepted that HBO can increase the dissolvedoxygen significantly, which may rectify the hypoxia incancers. However, HBO is often used once or twice dailyfor patients, and a hypoxic environment may form betweentwo exposures. As shown in this review, hypoxia is essentialfor the progression of cancers and related to the angiogen-esis. In addition, some studies have also shown that HBOtherapy can improve the angiogenesis after ischemic injury.Our previous study also revealed that HBO pretreatment canincrease the expression of hypoxia-inducible factor and itsdownstream factor vascular endothelial growth factor [2]which is a potent pro-angiogenic factor. Thus, HBO seemsto exert promotive effect on cancer growth.HBO and metastasisMetastasis is a complex process involving local cancer cellinvasion, entry into the blood or lymph vessels, and re-penetration and colonization at a distant site [3]. Theintegrity of vascular basement membrane (VBM) iscrucial for the cancer cell invasion. Suzuki et al. foundthat HBO enhanced transendothelial permeability in ratbrains [4]. In addition, HBO preconditioning was foundto increase the expression of matrix metalloproteinase(MMP) [5] which is may break the VBM. This maypotentiate the cancer cell invasion. Of interest, HBOtherapy may reduce the insult-induced expression ofMMP [6]. Thus, whether the effect of HBO on VBMintegrity depends on the microenvironment is not clear.If so, this may partially explain the absence of influenceof HBO on the metastasis of cancers.HBO and cancer stem cellsCancer stem cells (CSCs) are cancer cells that possesscharacteristics associated with normal stem cells, specifically

Effects of Hyperbaric Oxygen on Pain‐Related Behaviours and Nitric Oxide Synthase Expression in a Rat Model of Neuropathic Pain

Neuropathic pain is complex, and a satisfactory therapeutic method of treatment has yet to be developed; therefore, finding a new and effective therapeutic method is an important issue in the field of neuropathic pain. To determine the effects of hyperbaric oxygen (HBO) on pain-related behaviours and nitric oxide synthase (NOS) expression in a rat model of neuropathic pain. Forty male Sprague Dawley rats were randomly divided into five groups (eight rats per group) including control, sham operation, sciatic nerve with chronic constriction injury (CCI), HBO pretreatment (pre-HBO) and HBO post-treatment (post-HBO) groups. Pain-related behaviours and NOS expression in the spinal cord were compared among the five groups. Compared with the CCI group, the mechanical withdrawal threshold was significantly increased and thermal withdrawal latency was significantly extended in the pre-HBO and post-HBO groups (all P<0.05). After CCI, expression of spinal neuronal NOS and inducible NOS were increased. Expression of spinal neuronal NOS and inducible NOS were significantly decreased in the pre-HBO and post-HBO groups compared with the CCI group (all P<0.05). Spinal eNOS expression changed very little. HBO has been used as an effective and noninvasive method for the treatment of spinal cord injuries and high-altitude sickness, and in immunosuppression and stem-cell research; however, it has yet to be applied to the treatment of neuropathic pain. The present study indicated that HBO effectively increased mechanical withdrawal threshold and thermal withdrawal latency, demonstrating that HBO has therapeutic effects on neuropathic pain. HBO inhibits pain in rats with CCI through the regulation of spinal NOS expression.

Hyperbaric oxygen preconditioning protects skin from UV-A damage

Hyperbaric oxygen therapy (HBOT) is used for a number of applications, including the treatment of diabetic foot ulcers and CO poisoning. However, we and others have shown that HBOT can mobilize cellular antioxidant defenses, suggesting that it may also be useful under circumstances in which tissue protection from oxidative damage is desired. To test the protective properties of hyperbaric oxygen (HBO) on a tissue level, we evaluated the ability of a preconditioning treatment regimen to protect cutaneous tissue from UV-A-induced oxidative damage. Three groups of hairless SKH1-E mice were exposed to UV-A 3 days per week for 22 weeks, with two of these groups receiving an HBO pretreatment either two or four times per week. UV-A exposure increased apoptosis and proliferation of the skin tissue, indicating elevated levels of epithelial damage and repair. Pretreatment with HBO significantly reduced UV-A-induced apoptosis and proliferation. A morphometric analysis of microscopic tissue folds also showed a significant increase in skin creasing following UV-A exposure, which was prevented by HBO pretreatment. Likewise, skin elasticity was found to be greatest in the group treated with HBO four times per week. The effects of HBO were also apparent systemically as reductions in caspase-3 activity and expression were observed in the liver. Our findings support a protective function of HBO pretreatment from a direct oxidative challenge of UV-A to skin tissue. Similar protection of other tissues may likewise be achievable.

Glu tamate transporters and ischemic brain injury

Background Ischemia brain injury seriously threatens human life and health.Glutamate plays a major role in the pathogenesis of ischemia brain injury,and the regulation of glutamate conce4tration on the treatment of ischemic brain injury is important.Objective To find a treatment of ischemia brain injury,we investigate the relationship between brain ischemia injury and glutamate transporters,and the effect of a variety of pretreatments on glutamate transporters.Content This review summarizes the glutamate transporter's subtype,distribution,structure and function,and the relationship with ischemic brain injury and the neuroprotective effect of pretreatments.Trend Non-ischemic pretreatment,such as electroacupuncture pretreatment and hyperbaric oxygen pretreatment of cerebral ischemia,is effective and easy to implement.Glutamate transporters would be one of the protective mechanisms. Key words: Glutamate transporter; Ischemic brain damage

The influence and function mechanism of hyperbaric oxygen pretreatment on myocardial ischemia reperfusion injury in rats

Background and objectiveIn recent years, coronary atherosclerotic heart disease become the major disease which is harmful to human health with a rising the trend of incidence. The world health organisation...

Hyperbaric oxygen pretreatment according to the gas micronuclei denucleation hypothesis reduces neurologic deficit in decompression sickness in rats

During sudden or too rapid decompression, gas is released within supersaturated tissues in the form of bubbles, the cause of decompression sickness. It is widely accepted that these bubbles originate in the tissue from preexisting gas micronuclei. Pretreatment with hyperbaric oxygen (HBO) has been hypothesized to shrink the gas micronuclei, thus reducing the number of emerging bubbles. The effectiveness of a new HBO pretreatment protocol on neurologic outcome was studied in rats. This protocol was found to carry the least danger of oxygen toxicity. Somatosensory evoked potentials (SSEPs) were chosen to serve as a measure of neurologic damage. SSEPs in rats given HBO pretreatment before a dive were compared with SSEPs from rats not given HBO pretreatment and SSEPs from non-dived rats. The incidence of abnormal SSEPs in the animals subjected to decompression without pretreatment (1,013 kPa for 32 min followed by decompression) was 78%. In the pretreatment group (HBO at 304 kPa for 20 min followed by exposure to 1,013 kPa for 33 min and decompression) this was significantly reduced to 44%. These results call for further study of the pretreatment protocol in higher animals.

Combined effect of denucleation and denitrogenation on the risk of decompression sickness in rats

We previously hypothesized that the number of bubbles emerging on decompression from a dive, and the resultant risk of decompression sickness (DCS), may be reduced by a process whereby effective gas micronuclei that might otherwise have formed bubbles on decompression are shrunk and eliminated. In a procedure defined by us as denucleation, exposure to hyperbaric oxygen (HBO) would result in oxygen replacing the resident gas in the micronuclei, to be subsequently consumed by the mitochondria when the oxygen pressure is reduced. Support for the validity of our hypothesis may be found in our previous studies on the transparent prawn and the reduction of DCS in the rat. In all of these studies, HBO pretreatment was given before supersaturation with inert gas at high pressure. The purpose of the present study was to compare DCS outcome in rats that underwent nitrogen washout (denitrogenation) alone (9 min O(2) at 507 kPa) after exposure to air at high pressure (33 min at 1,266 kPa), and rats treated by both procedures (denitrogenation + denucleation; 8 min of O(2) breathing followed by 5 min air breathing, both at 507 kPa) after high-pressure air exposure. This was done with the same nitrogen load in both groups before the final decompression (a nitrogen pressure of 467 kPa in fatty and 488 kPa in aqueous tissue). Six of 20 rats in the denitrogenation + denucleation group died, compared with 13 in the denitrogenation group (P < 0.03). Three rats in the denitrogenation + denucleation group suffered mild DCS, recovering completely within 2 h of decompression. The present study indicates an advantage in considering both denitrogenation and denucleation before decompression. This may have practical application before escape from a disabled submarine, when aborting a technical dive, or in the preparation of aviators for high altitude.

Hyperbaric oxygen causes both antiinflammation and antipyresis in rabbits

Current study was attempted to assess whether hyperbaric oxygen pretreatment or treatment exerts its antipyresis by reducing circulating interleukin-6 and hypothalamic glutamate, hydroxyl radicals and prostaglandin-E 2 in rabbits. It was found that systemic administration of lipopolysaccharide induced increased levels of both core temperature and hypothalamic levels of glutamate, hydroxyl radicals, and prostaglandin E 2 accompanied by increased plasma levels of interleukin-6. The rise in both the core temperature and hypothalamic glutamate, hydroxyl radicals and prostaglandin-E 2 could also be induced by intracerebroventricular injection of interleukin-6. Pretreatment or treatment with hyperbaric oxygen significantly reduced the lipopolysaccharide-induced overproduction of circulating interleukin-6, and hypothalamic glutamate, prostaglandin E 2, and hydroxyl radicals. The febrile response caused by central administration of interleukin-6 could also be suppressed by hyperbaric oxygen pretreatment or treatment. Simultaneous administration of an anti-oxidant (e.g., N-acetyl- l-cysteine) significantly enhanced the antipyretic effects exerted by hyperbaric oxygen treatment. These results indicate that hyperbaric oxygen pretreatment or treatment may exert its antipyresis by inhibiting the glutamate–hydroxyl radicals–prostaglandin-E 2 pathways in the hypothalamus and circulating interleukin-6 accumulation during lipopolysaccharide-fever.