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Hypoxia exposure can result in different damage to the body. Especially, it have obvious effects on the nerve system. It can cause and aggravate cerebra learning and memory impairment through influencing some learning and memory related protin. This review focus on the introduction of learning memory related proteins, such as fatty Acid-binding Protein 5, estrogen-related receptor 酌, forkhead box p2, Iduna protein and tau protein and so on. Whats' more, it also respectively elaborate that the influence of hypobaric hypoxia environment to these proteins and to provide theory evidence for the clinical prevention and treatment of cerebrum learning and memory impairment caused for the high altitude environment. [ABSTRACT FROM AUTHOR]

This study examined whether normobaric hypoxia (NH) treatment is more efficacious for sustaining high-altitude (HA) acclimatization-induced improvements in ventilatory and hematologic responses, acute mountain sickness (AMS), and cognitive function during reintroduction to altitude (RA) than no treatment at all. Seventeen sea-level (SL) residents (age = 23 ± 6 yr; means ± SE) completed in the following order: 1) 4 days of SL testing; 2) 12 days of HA acclimatization at 4,300 m; 3) 12 days at SL post-HA acclimatization (Post) where each received either NH (n = 9, [Formula: see text] = 0.122) or Sham (n = 8; FIO2 = 0.207) treatment; and 4) 24-h reintroduction to 4,300-m altitude (RA) in a hypobaric chamber (460 Torr). End-tidal carbon dioxide pressure (PETCO2), hematocrit (Hct), and AMS cerebral factor score were assessed at SL, on HA2 and HA11, and after 20 h of RA. Cognitive function was assessed using the SynWin multitask performance test at SL, on HA1 and HA11, and after 4 h of RA. There was no difference between NH and Sham treatment, so data were combined. FIO2 (mmHg) decreased from SL (37.2 ± 0.5) to HA2 (32.2 ± 0.6), decreased further by HA11 (27.1 ± 0.4), and then increased from HA11 during RA (29.3 ± 0.6). Hct (%) increased from SL (42.3 ± 1.1) to HA2 (45.9 ± 1.0), increased again from HA2 to HA11 (48.5 ± 0.8), and then decreased from HA11 during RA (46.4 ± 1.2). AMS prevalence (%) increased from SL (0 ± 0) to HA2 (76 ± 11) and then decreased at HA11 (0 ± 0) and remained depressed during RA (17 ± 10). SynWin scores decreased from SL (1,615 ± 62) to HA1 (1,306 ± 94), improved from HA1 to HA11 (1,770 ± 82), and remained increased during RA (1,707 ± 75). These results demonstrate that HA acclimatization-induced improvements in ventilatory and hematologic responses, AMS, and cognitive function are partially retained during RA after 12 days at SL whether or not NH treatment is utilized. NEW & NOTEWORTHY This study demonstrates that normobaric hypoxia treatment over a 12-day period at sea level was not more effective for sustaining high-altitude (HA) acclimatization during reintroduction to HA than no treatment at all. The noteworthy aspect is that athletes, mountaineers, and military personnel do not have to go to extraordinary means to retain HA acclimatization to an easily accessible and relevant altitude if reexposure occurs within a 2-wk time period. [ABSTRACT FROM AUTHOR]

Objective: To study the characteristics of intestinal tract pathological injury of rats in hypobaric hypoxia at different high altitude. Methods: 30 male SD rats were randomly divided into 5 groups: Plain group (n=6), High-altitude (HA) 5000 m for 10 day group(n=6), HA 5000 m for 21day group(n=6), HA 6500 m for 10day group(n=6), HA 6500 m for 21day group (n=6). Rats were raised normally either in plain or simulated high altitude environment, at the corresponding time point, rats were euthanized, small intestines were harvested, fixed tissues were processed routinely into paraffin and sections were stained routinely with hematoxylin and eosin. Morphologic parameters were measured by optical microscope and then the pathological injury score were evaluated. Results: The pathological injury scores of jejunnm and ileum in the high altitude group were significantly higher than that of the plain group (P＜0.01), the pathological injury scores of jejunum, ileum and colon were significantly higher in the HA 5000 m for 21 day group than that of the HA 5000 m for 10 day group, but significant lower than that of the HA 6500 m for 21 day group, the pathological injury scores of jejunum, ileum and colon were significantly higher in the HA 6500 m for 10 day group than that of the HA 5000 m for 10 day group(P＜0.01, P＜0.05). The pathological injury scores of colon were significantly higher in the groups of the high altitude than the plain group except for the HA 5000 m for 10 day group (P＜0.01, P＜0.05). The pathological injury scores of jejunum had significant different with that of the colon in the HA 5000 m for 21 day group (P＜0.05); the pathological injury scores of both jejunum and ileum had significant different with that of the colon in the HA 6500 m for 21 day group(P＜0.05, P＜0.01). Conclusions: The injuries of the intestinal mucosa became serious with the with rising altitude and the stayed time, the intestinal injuries were more serious than that of colon at same situation, however there were no significant different between jejunum and ileum, the injuries of colon happened later than intestine, and they correlated with the stay time in the high altitude, which indicated that intestinal injury should be pay more attention in the early time of entering the hypobaric hypoxia environment of the high altitude. [ABSTRACT FROM AUTHOR]

12/15 Lipoxygenase has recently been described as potent propagator of oxidative stress and is closely associated with cognitive decline in neurodegenerative diseases. The mechanism/s behind 12/15 LOX involvement in cognitive deficits remain obscure. The current study has been designed to investigate the underlying role of 12/15LOX and effect of 12/15 LOX inhibition on hypobaric hypoxia-induced memory impairment and cholinergic deficits. Male Balb/c mice subjected to simulated hypobaric hypoxia/reoxygenation condition for 3 days showed marked working memory impairment concomitant with hippocampal neuronal damage and malondialdehyde production which were significantly attenuated by baicalein, a specific inhibitor of 12/15LOX. Hypobaric hypoxia-exposed mice had consistently increased expression of 12/15LOX and elevated 12(S) HETE levels in the hippocampus as well as plasma which were significantly mitigated following baicalein treatment. 12/15LOX inhibition also reduced hypobaric hypoxia-mediated upregulation of hippocampal HIF-1α protein expression along with reduction in expression of inflammatory genes. The inhibition of 12/15 LOX resulted in a significant decrease in NO levels in the hippocampal homogenate associated with downregulated iNOS, nNOS transcription but not eNOS speculating that 12/15 LOX is critically involved in HIF-1α, mediated by nitric oxide-induced neurotoxicity. We also observed a similar effect of 12/15 LOX inhibition on hippocampal COX2 expression. 12/15LOX inhibition could effectively modulate central cholinergic indices during hypobaric hypoxia by restoring mAChR-1, α7NAChR expression and AChE, ChAT activity in the hippocampus comparable to normal mice. We report here the mechanistic involvement of 12/15LOX in orchestrating hypoxia-associated neuronal damage and HIF-1α-dependent neuroinflammation resulting in cognitive decline. [ABSTRACT FROM AUTHOR]

Hypobaric hypoxia (HH) during airline travel induces several (patho-) physiological reactions in the human body. Whereas severe hypoxia is investigated thoroughly, very little is known about effects of moderate or short-term hypoxia, e.g. during airline flights. The aim of the present study was to analyse changes in serum protein expression and activation of signalling cascades in human volunteers staying for 30 min in a simulated altitude equivalent to airline travel. After approval of the local ethics committee, 10 participants were exposed to moderate hypoxia (simulation of 2400 m or 8000 ft for 30 min) in a hypobaric pressure chamber. Before and after hypobaric hypoxia, serum was drawn, centrifuged, and analysed by two-dimensional gel electrophoresis (2-DIGE) and matrix-assisted laser desorption/ionization followed by time-of-flight mass spectrometry (MALDI-TOF). Biological functions of regulated proteins were identified using functional network analysis (GeneMania®, STRING®, and Perseus® software). In participants, oxygen saturation decreased from 98.1 ± 1.3% to 89.2 ± 1.8% during HH. Expression of 14 spots (i.e., 10 proteins: ALB, PGK1, APOE, GAPDH, C1QA, C1QB, CAT, CA1, F2, and CLU) was significantly altered. Bioinformatic analysis revealed an association of the altered proteins with the signalling cascades "regulation of haemostasis" (four proteins), "metabolism" (five proteins), and "leukocyte mediated immune response" (five proteins). Even though hypobaric hypoxia was short and moderate (comparable to an airliner flight), analysis of protein expression in human subjects revealed an association to immune response, protein metabolism, and haemostasis. [ABSTRACT FROM AUTHOR]

The characteristics of the vacuum used in a low atmospheric pressure stunning system to stun (render unconscious) poultry prior to slaughter are described. A vacuum chamber is pumped by a wet screw compressor. The vacuum pressure is reduced from ambient atmospheric pressure to an absolute vacuum pressure of ∼250 Torr (∼33 kPa) in ∼67 sec with the vacuum gate valve fully open. At ∼250 Torr, the sliding gate valve is partially closed to reduce effective pumping speed, resulting in a slower rate of decreasing pressure. Ambient temperature affects air density and water vapor pressure and thereby oxygen levels and the time at the minimum total pressure of ∼160 Torr (∼21 kPa) is varied from ∼120 to ∼220 sec to ensure an effective stun within the 280 seconds of each cycle. The reduction in total pressure results in a gradual reduction of oxygen partial pressure that was measured by a solid-state electrochemical oxygen sensor. The reduced oxygen pressure leads to hypoxia, which is recognized as a humane method of stunning poultry. The system maintains an oxygen concentration of <5% for at least 2 minutes, which ensures that birds are irreversibly stunned. Calculated pump down (pressure versus time) data match experimental data very closely because the programmable logic controller and the human machine interface enable precise and accurate control. The vacuum system operates in the turbulent viscous flow regime, and is best characterized by absolute vacuum pressure rather than gauge pressure. Neither the presence of broiler chickens nor different fore-line pipe designs of four parallel commercial systems affected the pressure-time data. Water in wet air always reduces the oxygen concentrations to a value lower than in dry air. The partial pressure of water and oxygen were found to depend on the pump down parameters due to the formation of fog in the chamber and desorption of water from the birds and the walls of the vacuum chamber. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The purpose of the present study was to examine the influence of hypobaric hypoxia (HH) on a pilot's-light performance during exposure to simulated altitudes of 91,3048, and 4572 m (300,10,000, and 15,000 ft) and to monitor the pilot's physiological reactions. METHOD: In a single-blinded counter-balanced design, 12 male pilots were exposed to HH while flying in a flight simulator that had been placed in a hypobaric chamber. Flight performance of the pilots, pilot's alertness level, Spo2i heart rate (HR), minute ventilation (VE), and breathing frequency (BF) were measured. RESULTS: A significant difference was found in Flight Profile Accuracy (FPA) between the three altitudes. Post hoc analysis showed no significant difference in performance between 91 m and 3048 m. A trend was observed at 4572 m, suggesting a decrease in flight performance at that altitude. Significantly lower alertness levels were observed at the start of the flight at 4572 m compared to 91 m, and at the end of the flight at 4572 m compared to the start at that altitude. Spo2 and BF decreased, and HR increased significantly with altitude. DISCUSSION: The present study did not provide decisive evidence for a decrease in flight performance during exposure to simulated altitudes of 3048 and 4572 m. However, large interindividual variation in pilots'flight performance combined with a gradual decrease in alertness levels observed in the present study puts into question the ability of pilots to safely fly an aircraft while exposed to these altitudes without supplemental oxygen. [ABSTRACT FROM AUTHOR]

Protein kinase B (Akt) is a key enzyme in one of many neuroprotective signaling cascades in neurons that are activated during preconditioning by episodes of moderate hypoxia/ischemia. However, the data on the involvement of this anti-apoptotic pathway in mechanisms of the hypoxic tolerance induced by different experimental protocols are incomplete and contradictory. We exposed rats to moderate hypobaric hypoxia (3MHH) corresponding to an altitude of 5000 m above sea level three times (once a day for 2 hours). The 3MHH treatment is known as an effective stimulus for hypoxic brain tolerance. We used immunocytochemistry to study the dynamics of phosphorylation of Akt caused by 3MHH in various areas of the brain. It was found that each of the three 3MHH episodes quickly (within 3 hours) activated Akt phosphorylation in the neocortex, piriform cortex, and dentate gyrus of the hippocampus. Severe hypobaric hypoxia (SHH), the equivalent of a rise to 11000 m above sea level, did not produce this effect. Behavioral experiments on 3MHH-preconditioned rats subjected to subsequent SHH have shown that blocking the activity of PI3K/Akt with wortmannin during preconditioning had an anxiogenic effect typical of non-preconditioned animals that survived the SHH. Thus, we established the details of the involvement of the PI3K/Akt pathway in the neuroprotective mechanism of 3MHH-preconditioning for the first time. [ABSTRACT FROM AUTHOR]

Irarrázaval, Sebastián, Claudio Allard, Juan Campodónico, Druso Pérez, Pablo Strobel, Luis Vásquez, Inés Urquiaga, Guadalupe Echeverría, and Federico Leighton. Oxidative stress in acute hypobaric hypoxia. High Alt Med Biol. 18:128-134, 2017.-The effects of acute hypobaric hypoxia endured by mountaineers were studied, specifically as evidenced by acute mountain sickness (AMS) and oxidative stress damage. Ten male volunteers were exposed to acute hypobaric hypoxia, and AMS was evaluated through arterial oxygen saturation (SaO2), cardiac rate, and the Lake Louise Score (LLS). Oxidative stress was determined through blood profile tests performed 24 hours before and after high-altitude exposure, assessing the oxidative damage and antioxidant profiles. Dietary habits were assessed using the Chilean Mediterranean Diet Index. During ascent (i.e., first 8 hours), all volunteers presented AMS (LLS ≥3 points), as manifested by a median LLS increment of four points, a 15 bpm cardiac rate, and 17% decrease in SaO2. Additionally, plasma lipid oxidative damage increased after the expedition, as evaluated through malondialdehyde, which was directly correlated with the LLS ( R2 = 0.720, p = 0.003) and inversely correlated with SaO2 ( R2 = 0.436; p = 0.035) at a high altitude. Preascent carbonyl levels were inversely correlated to SaO2 ( R2 = 0.490; p = 0.008) and directly correlated to cardiac rate ( R2 = 0.225, p = 0.016) at a high altitude. Moreover, dietary habits were inversely correlated with increased carbonyls during the expedition ( R2 = 0.436; p = 0.047). In conclusion, acute hypobaric hypoxia induced AMS and an increment in oxidative stress markers 24 hours after altitude exposure in the volunteers. Furthermore, oxidative stress damage was related to AMS severity. Finally, volunteers with closer adherence to a Mediterranean diet presented a lower increase in oxidative damage during ascent, reflecting the potential preventive role of diet against AMS. [ABSTRACT FROM AUTHOR]

Ascent to elevated altitude, commonly achieved through flight, by climbing or by residence in highland regions, exposes the individual to reduced ambient pressure. Although there are physical manifestations of this exposure as a consequence of Boyle’s law, the primary physiological challenge is of hypobaric hypoxia. The acute physiological and longer-term adaptive responses of the cardiovascular, respiratory, haematological and neurological systems to altitude are described, together with an outline of the presentation and management of acute mountain sickness, high-altitude pulmonary oedema and high-altitude cerebral oedema. Whilst many millions experience modest exposure to altitude as a result of flight in pressurized aircraft, fewer individuals are exposed to increased ambient pressure. The pressure changes during diving and hyperbaric exposures result in greater changes in gas load and gas toxicity. Physiological effects include the consequences of increased work of breathing and redistribution of circulating volume. Neurological manifestations may be the direct result of pressure or a consequence of gas toxicity at depth. Increased tissue gas loads may result in decompression illness on return to surface or subsequent ascent in flight. [ABSTRACT FROM AUTHOR]

The hypobaric hypoxic environment in high-altitude areas often aggravates the severity of inflammation and induces brain injury as a consequence. However, the critical genes regulating this process remain largely unknown. The phosphatase wild-type p53-induced phosphatase 1 (WIP1) plays important roles in various physiological and pathological processes, including the regulation of inflammation in normoxia, but its functions in hypoxic inflammation-induced brain injury remain unclear. Here, we established a mouse model of this type of injury and found that WIP1 deficiency augmented the release of inflammatory cytokines in the peripheral circulation and brain tissue, increased the numbers of activated microglia/macrophages in the brain, aggravated cerebral histological lesions, and exacerbated the impairment of motor and cognitive abilities. Collectively, these results provide the first in vivo evidence that WIP1 is a critical neuroprotector against hypoxic inflammation-induced brain injury. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether there is a differential response at rest and following exercise to conditions of genuine high altitude (GHA), normobaric hypoxia (NH), hypobaric hypoxia (HH), and normobaric normoxia (NN).Method: Markers of sympathoadrenal and adrenocortical function [plasma normetanephrine (PNORMET), metanephrine (PMET), cortisol], myocardial injury [highly sensitive cardiac troponin T (hscTnT)], and function [N-terminal brain natriuretic peptide (NT-proBNP)] were evaluated at rest and with exercise under NN, at 3375 m in the Alps (GHA) and at equivalent simulated altitude under NH and HH. Participants cycled for 2 h [15-min warm-up, 105 min at 55% Wmax (maximal workload)] with venous blood samples taken prior (T0), immediately following (T120) and 2-h post-exercise (T240).Results: Exercise in the three hypoxic environments produced a similar pattern of response with the only difference between environments being in relation to PNORMET. Exercise in NN only induced a rise in PNORMET and PMET.Conclusion: Biochemical markers that reflect sympathoadrenal, adrenocortical, and myocardial responses to physiological stress demonstrate significant differences in the response to exercise under conditions of normoxia versus hypoxia, while NH and HH appear to induce broadly similar responses to GHA and may, therefore, be reasonable surrogates. [ABSTRACT FROM AUTHOR]

Aim: Rho kinase activation plays an important role in hypoxic pulmonary vasoconstriction and increased vascular resistance. The present study investigated changes in the level and activity of rho kinase isoform 2 (ROCK2) under acute hypobaric hypoxia exposure. For this, Wistar rats were taken as the model organism.Materials and Methods: Fifteen male Wistar rats (4-6 week old, 250 grams) were normalized with the surrounding environment by providing a 12/12 hour day and night acclimatization cycle. The rats were divided into 3 groups: (a) control group (no exposure, n = 5), (b) Group 1 (12 hour hypobaric-hypoxia exposure, n = 5) and (c) Group 2 (12 hour hypobaric hypoxia and 12 hour normobaric normoxia exposure, n = 5). A change in behavior of the animals was noted before sacrifice. Blood was collected from the beating heart of the anesthetized animal. Lungs were dissected out and used to estimate the levels and activity of ROCK2 in different groups using commercially available kits. Lung histology was evaluated by immunohistochemistry.ROCK2gene expression was studied in the blood and lungs using quantitative PCR.Results and Conclusions: Control and Group 2 animals had an active movement while the Group 1 animals were sluggish before the sacrifice. Formation of a large perivascular edema cuff and collagen deposition in lungs of Group 1 and a reduction in Group 2 was observed. The protein levels and activities of ROCK2 were increased in Group 1 (p< 0.05) and became normal in Group 2 which was akin to control group animals.ROCK2expression in PBMCs was increased in Group 1 (10.7 fold, p = 0.005) and was decreased in Group 2 (5.5 fold, p = 0.02). The outcomes establish that acute hypobaric hypoxia augments ROCK2 protein level and activity. [ABSTRACT FROM AUTHOR]

We studied the effects of different modes of hypobaric hypoxia on the content of epigenetic factors acH3K24, meH3K9, and meDNA modulating conformational characteristics of chromatin and gene expression in neurons of associative complex of rat parietal neocortex. Severe destructive hypoxia dramatically reduced the level of acH3K24 in 3 h after the end of exposure and increased meH3K9 and meDNA content. By contrast, 3-fold (but not single) adaptive exposure to moderate hypobaric hypoxia that produced a neuroprotective effect enhanced neuronal acH3K24 expression and decreased both meH3K9 and meDNA levels. Elevated acH3K24 content facilitates, while increased content of meH3K9 hampers binding of transcription factors to the target genes. At the same time, increased expression of meDNA suppresses transcription. The role of modification of epigenetic mechanisms in the regulation of proadaptive genes under the effects of hypoxic exposure according to various protocols is discussed. [ABSTRACT FROM AUTHOR]

Objective To study the protective effects of the total bakkenolides from P. tricholobus on high altitude hypoxia. Method Normobaric hypoxia model and acute hypobaric hypoxia model in mice, hypobaric hypoxia model in rats were established for this study. Survival time and survival rate of mice were recorded. The level of blood sugar and glycogen, adenosine triphosphate (ATP), lactic acid (LD), lactic dehydrogenase (LDH) were detected in different organs of rats. Results The total bakkenolides significantly prolonged the survival time of mice in normobaric hypoxia model and reduced the death rate of mice in acute hypobaric hypoxia model. The total bakkenolides suppressed blood sugar level in rats and increased the glycogen level in rat liver, skeletal muscle and myocardium. It also elevated the ATP content in rat brain, liver, skeletal muscle and myocardium. Meanwhile, the content of LD in plasma, skeletal muscle, myocardium and LDH level in myocardium were reduced. Conclusion The total bakkenolides from P. tricholobus have protective effect on normobaric hypoxia model and acute hypobaric hypoxia model in mice as well as hypobaric hypoxia model in rats. Its anti-hypoxia efficacy at high altitude may relate to the increased blood sugar, glycogen, and ATP level and reduced LD, LDH level in major organs. [ABSTRACT FROM AUTHOR]

Van Iterson, Erik H., Eric M. Snyder, and Bruce D. Johnson. The influence of 17 hours of normobaric hypoxia on parallel adjustments in exhaled nitric oxide and airway function in lowland healthy adults. High Alt Med Biol. 18:1-10, 2017.-Currently, there is a disparate understanding of the role that normobaric hypoxia plays in affecting nitric oxide (NO) measured in exhaled air (eNO) and airway function in lowland healthy adults. Compared to normobaric normoxia, this study aimed to test the effect of 17 hours of normobaric hypoxia on relationships between eNO and airway function in healthy adults. In a crossover study including 2 separate visits, 26 lowland healthy Caucasian adults performed eNO and pulmonary function tests on visit 1 in normobaric normoxia, while repeating all tests on visit 2 following 17 hours of normobaric hypoxia (12.5% O2). Compared to normobaric normoxia, eNO (29 ± 24 vs. 36 ± 28 ppb), forced expiratory volume in one second (FEV1) (4.1 ± 0.7 vs. 4.3 ± 0.8 L), mean forced expiratory flow between 25% and 75% FVC (FEF25-75) (3.9 ± 1.0 vs. 4.2 ± 1.2 L/s), and forced expiratory flow at 75% FVC (FEF75) (2.0 ± 0.7 vs. 2.3 ± 0.8 L/s) increased in normobaric hypoxia, respectively (all p < 0.05). Correlations at normoxia between eNO and FEV1 ( r = 0.39 vs. 0.44), FEF25-75 ( r = 0.51 vs. 0.51), and FEF75 ( r = 0.53 vs. 0.55) persisted as both parameters increased in hypoxia, respectively. For the first time, these data suggest that 17 hours of hypoxic breathing in the absence of low ambient pressure contribute to increased eNO and airway function in lowland healthy adults. [ABSTRACT FROM AUTHOR]

Rationale: Exposures to simulated altitude (normobaric hypoxia, NH) are frequently used in preparation for mountaineering activities at real altitude (hypobaric hypoxia, HH). However, physiological responses to exercise in NH and HH may differ. Unfortunately clinically useful information on such differences is largely lacking. This study therefore compared exercise responses between a simulated hike on a treadmill in NH and a similar field hike in HH. Methods: Six subjects (four men) participated in two trials, one in a NH chamber and a second in HH at an altitude of 4,205 m on the mountain Mauna Kea. Subjects hiked in each setting for 7 h including breaks. In NH, hiking was simulated by walking on a treadmill. To achieve maximal similarity between hikes, subjects used the same nutrition, clothes, and gear weight. Measurements of peripheral oxygen saturation (SpO2), heart rate (HR) and barometrical pressure (PB)/inspired oxygen fraction (FiO2) were taken every 15 min. Acute mountain sickness (AMS) symptoms were assessed using the Lake-Louise-Score at altitudes of 2,800, 3,500, and 4,200 m. Results: Mean SpO2 values of 85.8% in NH were significantly higher compared to those of 80.2% in HH (p = 0.027). Mean HR values of 103 bpm in NH were significantly lower than those of 121 bpm in HH (p = 0.029). AMS scores did not differ significantly between the two conditions. Conclusion: Physiological responses to exercise recorded in NH are different from those provoked by HH. These findings are of clinical importance for subjects using simulated altitude to prepare for activity at real altitude. [ABSTRACT FROM AUTHOR]

In this work, using a rat model combining ischemia and hypobaric hypoxia (IH), we evaluate the relationships between the antioxidant melatonin and the cerebral nitric oxide/nitric oxide synthase (NO/NOS) system seeking to ascertain whether melatonin exerts its antioxidant protective action by balancing this key pathway, which is highly involved in the cerebral oxidative and nitrosative damage underlying these pathologies. The application of the IH model increases the expression of the three nitric oxide synthase (NOS) isoforms, as well as nitrogen oxide (NOx) levels and nitrotyrosine (n-Tyr) impacts on the cerebral cortex. However, melatonin administration before IH makes nNOS expression response earlier and stronger, but diminishes iNOS and n-Tyr expression, while both eNOS and NOx remain unchanged. These results were corroborated by nicotine adenine dinucleotide phosphate diaphorase (NADPH-d) staining, as indicative of in situ NOS activity. In addition, the rats previously treated with melatonin exhibited a reduction in the oxidative impact evaluated by thiobarbituric acid reactive substances (TBARS). Finally, IH also intensified glial fibrillary acidic protein (GFAP) expression, reduced hypoxia-inducible factor-1alpha (HIF-1α), but did not change nuclear factor kappa B (NF-κB); meanwhile, melatonin did not significantly affect any of these patterns after the application of the IH model. The antioxidant melatonin acts on the NO/NOS system after IH injury balancing the release of NO, reducing peroxynitrite formation and protecting from nitrosative/oxidative damage. In addition, this paper raises questions concerning the classical role of some controversial molecules such as NO, which are of great consequence in the final fate of hypoxic neurons. We conclude that melatonin protects the brain from hypoxic/ischemic-derived damage in the first steps of the ischemic cascade, influencing the NO/NOS pathway and reducing oxidative and nitrosative stress. [ABSTRACT FROM AUTHOR]

Background: Rhodiola crenulata is traditionally used as a folk medicine in Tibet for preventing high-altitude illnesses, including sudden cardiac death (SCD). The cardio-protective effects of Rhodiola crenulata root extract (RCE) against hypoxia in vivo have been recently confirmed. However, the way in which RCE produces these effects remains unclear. The present study is designed to confirm the protective effects of RCE on the heart in acute hypobaric hypoxia exposure and examine the mechanisms by which this occurs. Methods: Sprague--Dawley (SD) rats were pretreated with or without RCE and then exposed to a simulated altitude of 8000 m in a hypobaric hypoxia chamber for 9 h. The expression of cardiac arginase 1 (Arg-1) and endothelial nitric oxide synthase (eNOS) and the activity of associated signaling pathways was examined. Results: Hypoxia reduced cardiac eNOS phosphorylation and increased Arg-1 expression, but both responses were reversed by RCE pre-treatment. In addition, RCE decreased the hypoxia-induced oxidative stress markers of reactive oxygen species (ROS) production, malondialdehyde (MDA) level, and protein carbonyl content. Furthermore, RCE protected cardiomyocytes from hypoxia-induced cardiac apoptosis and restored the phosphorylation level of AKT and p38 MAPK as well as the superoxide dismutase 2 (SOD2) content in hypoxic animals. Conclusion: The findings provide evidence that the effects of Rhodiola crenulata against altitude illness are partially mediated by modulation of eNOS and Arg-1 pathways in the heart. [ABSTRACT FROM AUTHOR]

Rat brain and heart display different endogenous protective responses against hypobaric hypoxia in an age-dependent way. The aim of the present work was to evaluate the effects of acute hypobaric hypoxia (HH, 48 h) on brain and heart mitochondrial function as well as the participation of nitric oxide (NO) in old rats (22-month old). Cortical mitochondria from rats exposed to HH decreased respiratory rates (37 %, state 3) and membrane potential (20 %), but NO and H 2 O 2 production increased by 48 %, and 23 %, respectively. Hippocampal mitochondria preserved O 2 consumption and H 2 O 2 production, decreased membrane potential (18 %) and increased NO production (46 %). By contrast, HH decreased NO production (53 %) in mitochondria from left heart ventricles associated with increased cytochrome oxidase activity (39 %) and decreased NADPH oxidase activity (31 %). Also, a tendency to increase complex I-III (24 %) and complex II-III (65 %) activity was observed. In conclusion, after HH hippocampal and cortical mitochondria showed mild uncoupling and increased NO production. However, only the hippocampus preserved O 2 consumption and H 2 O 2 levels. Interestingly, heart mitochondria showed a decreased ROS production through increased cytochrome oxidase activity associated with a decrease in NO production. This may be interpreted as a self-protective mechanism against hypoxia. • 48 h hypobaric hypoxia induces differential tissue mitochondrial responses in senile rats. • Brain cortical mitochondria decrease respiratory rates and increase H 2 O 2 production. • Hippocampus of senile rats preserve mitochondrial O 2 consumption and H 2 O 2 production. • Left heart ventricle increases O 2 availability and decreases ROS. • Changes in NO production would be responsible for the differential tissue responses [ABSTRACT FROM AUTHOR]

Acute mountain sickness (AMS) typically peaks following the first night at high altitude (HA) and resolves over the next 2-3 days, but the impact of active ascent on AMS is debated. To determine the impact of ascent conditions on AMS, 78 healthy Soldiers (means ± SD; age = 26 ± 5 yr) were tested at baseline residence, transported to Taos, NM (2,845 m), hiked ( n = 39) or were driven ( n = 39) to HA (3,600 m), and stayed for 4 days. AMS-cerebral (AMS-C) factor score was assessed at HA twice on day 1 (HA1), five times on days 2 and 3 (HA2 and HA3), and once on day 4 (HA4). If AMS-C was ≥0.7 at any assessment, individuals were AMS susceptible (AMS+; n = 33); others were nonsusceptible (AMS-; n = 45). Daily peak AMS-C scores were analyzed. Ascent conditions (active vs. passive) did not impact the overall incidence and severity of AMS at HA1-HA4. The AMS+ group, however, demonstrated a higher ( P < 0.05) AMS incidence in the active vs. passive ascent cohort on HA1 (93% vs. 56%), similar incidence on HA2 (60% vs. 78%), lower incidence ( P < 0.05) on HA3 (33% vs. 67%), and similar incidence on HA4 (13% vs. 28%). The AMS+ group also demonstrated a higher ( P < 0.05) AMS severity in the active vs. passive ascent cohort on HA1 (1.35 ± 0.97 vs. 0.90 ± 0.70), similar score on HA2 (1.00 ± 0.97 vs. 1.34 ± 0.70), and lower ( P < 0.05) score on HA3 (0.56 ± 0.55 vs. 1.02 ± 0.75) and HA4 (0.32 ± 0.41 vs. 0.60 ± 0.72). Active compared with passive ascent accelerated the time course of AMS with more individuals sick on HA1 and less individuals sick on HA3 and HA4. NEW & NOTEWORTHY This research demonstrated that active ascent accelerated the time course but not overall incidence and severity of acute mountain sickness (AMS) following rapid ascent to 3,600 m in unacclimatized lowlanders. Active ascenders became sicker faster and recovered quicker than passive ascenders, which may be due to differences in body fluid regulation. Findings from this well-controlled large sample-size study suggest that previously reported discrepancies in the literature regarding the impact of exercise on AMS may be related to differences in the timing of AMS measurements between studies.

Hypobaric hypoxia (HH) leads to various adverse effects on skeletal muscles, including atrophy and reduced oxidative work capacity. However, the effects of HH on muscle fatigue resistance and myofiber remodeling are largely unexplored. Therefore, the present study aimed to explore the impact of HH on slow-oxidative fibers and to evaluate the ameliorative potential of exercise preconditioning and nanocurcumin formulation on muscle anti-fatigue ability. C2C12 cells (murine myoblasts) were used to assess the effect of hypoxia (0.5%, 24 h) with and without the nanocurcumin formulation (NCF) on myofiber phenotypic conversion. To further validate this hypothesis, male Sprague Dawley rats were exposed to a simulated HH (7620 m) for 7 days, along with NCF administration and/or exercise training. Both in vitro and in vivo studies revealed a significant reduction in slow-oxidative fibers (p < 0.01, 61% vs. normoxia control) under hypoxia. There was also a marked decrease in exhaustion time (p < 0.01, 65% vs. normoxia) in hypoxia control rats, indicating a reduced work capacity. Exercise preconditioning along with NCF supplementation significantly increased the slow-oxidative fiber proportion and exhaustion time while maintaining mitochondrial homeostasis. These findings suggest that HH leads to an increased transition of slow-oxidative fibers to fast glycolytic fibers and increased muscular fatigue. Administration of NCF in combination with exercise preconditioning restored this myofiber remodeling and improved muscle anti-fatigue ability., (© 2023. The Author(s) under exclusive licence to University of Navarra.)

With the increasing of altitude activities from low-altitude people, the study of high altitude cerebral edema (HACE) has been revived. HACE is a severe acute mountain sickness associated with exposure to hypobaric hypoxia at high altitude, often characterized by disturbance of consciousness and ataxia. As for the pathogenesis of HACE, previous studies suggested that it might be related to the disorder of cerebral blood flow, the destruction of blood-brain barrier and the injury of brain parenchyma cells caused by inflammatory factors. In recent years, studies have confirmed that the imbalance of REDOX homeostasis is also involved in the pathogenesis of HACE, which mainly leads to abnormal activation of microglia and destruction of tight junction of vascular endothelial cells through the excessive production of mitochondrial-related reactive oxygen species. Therefore, this review summarizes the role of REDOX homeostasis and the potential of the treatment of REDOX homeostasis in HACE, which is of great significance to expand the understanding of the pathogenesis of HACE. Moreover, it will also be helpful to further study the possible therapy of HACE related to the key link of REDOX homeostasis., Competing Interests: All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Li et al.)

Objective: The hypersensitivity of the kidney makes it susceptible to hypoxia injury. The involvement of neutrophil extracellular traps (NETs) in renal injury resulting from hypobaric hypoxia (HH) has not been reported. In this study, we aimed to investigate the expression of NETs in renal injury induced by HH and the possible underlying mechanism., Methods: A total of 24 SD male rats were divided into three groups (n=8 each): normal control group, hypoxia group and hypoxia+pyrrolidine dithiocarbamate (PDTC) group. Rats in hypoxia group and hypoxia+PDTC group were placed in animal chambers with HH which was caused by simulating the altitude at 7000 meters (oxygen partial pressure about 6.9 kPa) for 7 days. PDTC was administered at a dose of 100 mg/kg intraperitoneally once daily for 7 days. Pathological changes of the rat renal tissues were observed under a light microscope; the levels of serum creatinine (SCr), blood urea nitrogen (BUN), cell-free DNA (cf-DNA) and reactive oxygen species (ROS) were measured; the expression levels of myeloperoxidase (MPO), citrullinated histone H3 (cit-H3), B-cell lymphoma 2 (Bcl-2), Bax, nuclear factor kappa B (NF-κB) p65 and phospho-NF-κB p65 (p-NF-κB p65) in rat renal tissues were detected by qRT-qPCR and Western blotting; the localization of NF-κB p65 expression in rat renal tissues was observed by immunofluorescence staining and the expression changes of NETs in rat renal tissues were detected by multiplex fluorescence immunohistochemical staining., Results: After hypoxia, the expression of NF-κB protein in renal tissues was significantly increased, the levels of SCr, BUN, cf-DNA and ROS in serum were significantly increased, the formation of NETs in renal tissues was significantly increased, and a large number of tubular dilatation and lymphocyte infiltration were observed in renal tissues. When PDTC was used to inhibit NF-κB activation, NETs formation in renal tissue was significantly decreased, the expression level of Bcl-2 in renal tissues was significantly increased, the expression level of Bax was significantly decreased, and renal injury was significantly alleviated., Conclusion: HH induces the formation of NETs through the NF-κB signaling pathway, and it promotes apoptosis and aggravates renal injury by decreasing Bcl-2 and increasing Bax expression., (© 2023. Huazhong University of Science and Technology.)

Apte, Chandrashekhar V. Barometric pressure at high altitude: revisiting West's prediction equation, and more. High Alt Med Biol. 24:85-93, 2023. Introduction: Since an earlier prediction equation to calculate barometric pressure at a given altitude had been tested against limited barometric pressure observations, its accuracy needed to be re-validated against additional pressure observations. Methods: Five-year (2016-2020) barometric pressure and altitude data were downloaded from an open-source website for 25 select locations. The calculated predicted pressure was compared with mean 5-year, mean monthly, and mean daily pressures. Percent prediction error and root mean square errors were used to assess accuracy of the prediction equation. Results: The original prediction equation was accurate to within 1% for locations only within 22° latitude. It was increasingly inaccurate at higher latitudes and also for means based on shorter time spans (e.g., mean monthly and daily pressures). A new prediction equation was proposed by developing a model using downloaded data. The new equation resulted in more accurate predictions for all latitudes and all time spans. The new equation also performed well when tested at seven new locations. Conclusions: Ideally, medical professionals at high altitude should rely on actual barometric pressure observations to assess hypoxic risk. In the absence of actual measurements, the suggested new prediction equation may be used to estimate, with some limitations, the ambient barometric pressure at latitudes below 47° and altitudes up to about 4,700 m.

Kammerer, Tobias, Anna Walzl, Thomas Müller, Philipp Groene, Giulia Roveri, Rachel Turner, Johanna Roche, Hannes Gatterer, Christoph Siebenmann, and Simon T. Schäfer. Effects of hypobaric hypoxia on coagulation in healthy subjects exposed to 3,500 m altitude. High Alt Med Biol . 24:94-103, 2023. Background: Hypoxia is discussed as a trigger for prothrombotic changes both in intensive care and high altitude medicine. This research study aimed to evaluate the effect of isolated hypobaric hypoxia (HH) on coagulation in females in a highly standardized setting. Methods: Twelve healthy female subjects were studied under HH (equivalent to 3,500 m) and normoxia (NX) during two 4-day sojourns, in a strictly controlled crossover design. Nutrition, fluid intake, hormonal status (i.e., menstrual cycle variation), and physical stress were standardized. Functional coagulation and blood lysis were measured by viscoelastometry and compared between HH and NX. In addition, plasma-based coagulation tests (PBCTs), namely prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII coagulation activity (FVIII:C), von Willebrand factor antigen (vWF:Ag), and von Willebrand factor ristocetin cofactor activity (vWF:RCo) were measured. Results: Neither for Viscoelastic Haemostatic Assays nor for PBCTs significant changes were found for HH compared with NX (all p  > 0.05). Specifically, the lysis ability, as well as clotting time, clot formation, clot amplitude, and maximum clot firmness unchanged were similar between HH and NX. This also applied to all other variables. Conclusion: We demonstrate that moderate HH per se has no influence on blood coagulation in healthy females.

Inadequate oxygen availability-for instance at high altitudes-leads to hippocampal neurodegeneration and memory impairment. Although oxidative stress is one factor, the mechanism underlying the effects of hypobaric hypoxia (HH) are unclear, and effective strategies for preventing the resultant damage to the brain are limited. In the present study, we demonstrate that ingesting dihydromyricetin (DM) protects against memory impairment in adult rats subjected to HH for 7 days, equivalent to an altitude of 5000 m above sea level. Moreover, DM treatment stimulated mitochondrial biogenesis and improved mitochondrial morphology and function, suppressed the generation of reactive oxygen species, and reduced lipid peroxidation in the hippocampus. In HT-22 cells exposed to hypoxic conditions, the neuroprotective effects of DM were shown to be exerted via attenuation of oxidative stress through sirtuin 3-induced forkhead box O3 deacetylation. [ABSTRACT FROM AUTHOR]