Search

Taking into account the importance of aerobic metabolism in brain, the aim of the present work was to evaluate mitochondrial function in cerebral cortex and hippocampus in a model of sustained hypobaric hypoxia (5000 m simulated altitude) during a short (1 mo) and a long (7 mo) term period, in order to precise the mechanisms involved in hypoxia acclimatization. Hippocampal mitochondria from rats exposed to short-term hypobaric hypoxia showed lower respiratory rates than controls in both states 4 (45%) and 3 (41%), and increased NO production (1.3 fold) as well as eNOS and nNOS expression associated to mitochondrial membranes, whereas mitochondrial membrane potential decreased (7%). No significant changes were observed in cortical mitochondria after 1 mo hypobaric hypoxia in any of the mitochondrial functionality parameters evaluated. After 7 mo hypobaric hypoxia, oxygen consumption was unchanged as compared with control animals both in hippocampal and cortical mitochondria, but mitochondrial membrane potential decreased by 16% and 8% in hippocampus and cortex respectively. Also, long-term hypobaric hypoxia induced an increase in hippocampal NO production (0.7 fold) and in eNOS expression. A clear tendency to decrease in H 2 O 2 production was observed in both tissues. Results suggest that after exposure to hypobaric hypoxia, hippocampal mitochondria display different responses than cortical mitochondria. Also, the mechanisms responsible for acclimatization to hypoxia would be time-dependent, according to the physiological functions of the brain studied areas. Nitric oxide metabolism and membrane potential changes would be involved as self-protective mechanisms in high altitude environment. [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]

BACKGROUND: Effects of hypobarism and hypoxia on visual performance and mainly on contrast sensitivity (CS) are well known. The purpose of this study was to compare the adjustments of corneal thickness in hypobaric hypoxia conditions with changes in contrast sensitivity. METHODS: There were 12 healthy, emmetropic subjects assigned to the 14th Wing Aircrew based in Pratica di Mare AFB (Rome, Italy) who were evaluated for changes occurring in central corneal thickness (CCT), measured by portable ultrasonic pachymeter, and CS, assessed after reading the standard Pelli-Robson charts, during modification of atmospheric pressure and, therefore, of oxygen partial pressure. RESULTS: Hypobaric hypoxia conditions in pilots raised CCT (550 µm to 600 µm) and reduced CS (1.95 log to 1.05 log) in a statistically significant result. DISCUSSION: The study demonstrated that hypoxia and variations of atmospheric pressure may produce corneal edema, including changes of CCT and, correctively, CS reduction. [ABSTRACT FROM AUTHOR]

Aim: Oxidative stress during early phase of acute hypobaric hypoxia may predispose an individual susceptible to critical altitude illness while ascending rapidly to high altitudes. We assessed the biochemical parameters and examined the histological changes to check the oxidative stress status of the lung tissues of Sprague-Dawley rats, susceptible and tolerant to acute hypobaric hypoxia during early phase of exposure. Methods: A simulated acute hypobaric hypoxia of one hour at 9144 m and 24 °C was given to susceptible male, normal male (moderate), tolerant male and female groups of rats. Reactive oxygen species (ROS) levels, malondialdehdye (MDA) and oxidized glutathione (GSSG) content, total catalase (CAT) activity, superoxide dismutase (SOD) inhibitory activity and glutathione peroxidase (Gpx) activity were measured using standard protocols in lung tissue samples isolated from the different groups of hypoxia stressed and normoxic rats. Histological changes were also studied by haematoxylin and eosin staining in these tissue samples. Results: Marked neutrophil infiltration, alveolar wall collapse and interstitium thickening was visible in susceptible lung tissues showing maximum ROS levels, MDA equivalents and GSSG activity comparative to other test samples. Although SOD inhibitory activity increased in susceptible and normal groups in comparison to both the tolerant groups, however, Gpx activity showed an opposite trend. Catalase activity was recorded highest in the normal rat group as compared to other groups. Conclusion : Increased neutrophil infiltration coupled with higher oxidant's levels in susceptible rat lungs, and increased antioxidant enzyme activity in normal and tolerant rats demonstrate the differential physiological states in lung tissues, which could be diagnosed even in early phase of acute hypobaric hypoxia stress. [ABSTRACT FROM AUTHOR]

Recent preclinical and clinical studies have unfolded the potential of pharmacological modulation of activities of sphingosine-1-phosphate (S1P) receptors and S1P metabolizing enzymes for the development of therapeutic interventions against a variety of pathologies. An understanding of differential and temporal effects of hypoxia exposure on the key components of S1P signalling would certainly aid in designing improved drug development strategies in this direction. In view of this, the aim of the present study was to assess the effect of progressive hypobaric hypoxia exposure on expression of S1P receptors (S1PR) and specific activities of S1P synthesizing enzymes-neutral sphingomyelinase (nSMase) and sphingosine kinase (Sphk) in pulmonary and cerebral tissues of rats exposed to simulated altitude of 21,000 feet in an animal decompression chamber. Along with this, development of cerebral and pulmonary edema and markers of inflammation were studied at 12, 24, and 48 h to validate our study model of hypobaric hypoxia-induced stress. The protein expression of S1PR and activities of Sphk and nSMase enzymes were observed to be dramatically affected by simulated hypobaric hypoxia exposure, concurrent with deterioration of pathology, with 12 h of exposure appearing to be the most critical of the various time points studied. [ABSTRACT FROM AUTHOR]

Mellor, Adrian, Christopher Boos, David Holdsworth, Joe Begley, David Hall, Andrew Lumley, Anne Burnett, Amanda Hawkins, John O'Hara, Stephen Ball, and David Woods. Cardiac biomarkers at high altitude. High Alt Med Biol 15:452-458, 2014.- Background: Classically, biomarkers such as the natriuretic peptides (NPs) BNP/NT-proBNP are associated with the diagnosis of heart failure and hs-cTnT with acute coronary syndromes. NPs are also elevated in pulmonary hypertension. High pulmonary artery systolic pressure (PASP) is a key feature of high altitude pulmonary edema (HAPE), which may be difficult to diagnose in the field. We have previously demonstrated that NPs are associated with high PASP and the presence of acute mountain sickness (AMS) in a small cohort at HA. We aimed to investigate the utility of several common cardiac biomarkers in diagnosing high PASP and AMS. Methods: 48 participants were assessed post-trekking and at rest at three altitudes: 3833 m, 4450 m, and 5129 m. NPs, hs-cTnT and hsCRP, were quantified using immunoassays, PASP was measured by echocardiography, and AMS scores were recorded. Results: Significant changes occurred with ascent in NPs, hs-cTnT, hsCRP (all p<0.001) and PASP ( p=0.006). A high PASP (≥40 mm Hg) was associated with higher NPs, NT-proBNP: 137±195 vs. 71.8±68 ( p=0.001); BNP 15.3±18.1 vs. 8.7±6.6 ( p=0.001). NPs were significantly higher in those with AMS or severe AMS vs. those without (severe AMS: NT-proBNP: 161.2±264 vs. 76.4±82.5 ( p=0.008)). The NPs correlated with hsCRP. cTnT increased with exercise at HA and was also higher in those with a high PASP (13.8±21 vs. 7.8±6.5, p=0.018). Conclusion: The NPs and hs-cTnT are associated with high PASP at HA and the NPs with AMS. [ABSTRACT FROM AUTHOR]

Background & objectives: Low availability of oxygen at high altitudes has a great impact on the human life processes. There is a widespread interest and need to find out protein(s) that are possibly involved in mediating tolerance to hypobaric hypoxia. We undertook this study to identify and characterize protein expression in plasma of hypoxia susceptible and tolerant rats. Methods: Male albino Sprague Dawley rats were segregated into susceptible and tolerant groups on the basis of their gasping time when exposed to simulated hypobaric hypoxia of 32,000 ft (9,754 m) at 32ºC. Comparative proteome profiling of blood plasma of hypoxia susceptible and tolerant individuals was performed using 2-dimentional (2-D) gel electrophoresis. Results: Three proteins with higher expression levels were selected separately from tolerant and susceptible samples. Characterization of these proteins from tolerant sample using MALDI-TOF/TOF and MASCOT search indicated their homology with two different super-families viz. NADB-Rossmann superfamily (Rab GDP dissociation inhibitor β) and Transferrin superfamily (two Serotransferrins), having potential role in imparting tolerance against hypoxia. Three high level upregulated proteins were characterized from blood plasma of hypoxia susceptible animals showing similarity with threonine tRNA ligase (mitochondrial), carbohydrate sulphotransferase 7 and aspartate tRNA ligase (cytoplasmic) that play a role in ATP binding, carbohydrate metabolism and protein biosynthesis, respectively. Interpretation & conclusions: Our results indicated that rats segregated into hypoxia sensitive and tolerant based on their gasping time showed differential expression of proteins in blood plasma. Characterization of these differentially expressed proteins will lead to better understanding of molecular responses occurring during hypoxia and subsequently development of biomarkers for categorization of hypoxia susceptible and tolerant individuals. [ABSTRACT FROM AUTHOR]

High altitudes or exposure to hypoxia leads to female reproductive disorders. Circadian clocks are intrinsic time-tracking systems that enable organisms to adapt to the Earth's 24-h light/dark cycle, which can be entrained by other environmental stimuli to regulate physiological and pathological responses. In this study, we focused on whether ovarian circadian clock proteins were involved in regulating female reproductive dysfunction under hypoxic conditions. Hypobaric hypoxia was found to induce a significantly prolonged estrous cycle in female mice, accompanied by follicular atresia, pituitary/ovarian hormone synthesis disorder, and decreased LHCGR expression in the ovaries. Under the same conditions, the levels of the ovarian circadian clock proteins, CLOCK and BMAL1, were suppressed, whereas E4BP4 levels were upregulated. Results from granulosa cells (GCs) further demonstrated that CLOCK: BMAL1 and E4BP4 function as transcriptional activators and repressors of LHCGR in ovarian GCs, respectively, whose responses were mediated by HIF1ɑ-dependent (E4BP4 upregulation) and ɑ-independent (CLOCK and BMAL1 downregulation) manners. The LHCGR agonist was shown to efficiently recover the impairment of ovulation-related gene ( EREG and PGR ) expression in GCs induced by hypoxia. We conclude that hypoxia exposure causes dysregulation of ovarian circadian clock protein (CLOCK, BMAL1, and E4BP4) expression, which mediates female reproductive dysfunction by impairing LHCGR-dependent signaling events. Adjusting the timing system or recovering the LHCGR level in the ovaries may be helpful in overcoming female reproductive disorders occurring in the highlands., Competing Interests: The 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., (Copyright © 2022 Ding, Lu, Huang, Xing, Hou, Wang, Zhang, Wang, Zhang, Zhang, Meng, Liu, Liu, Zhao and Song.)

Sharma, Vandana, Rajeev Varshney, and Niroj Kumar Sethy. Identification of suitable reference genes for lowlanders exposed to high altitude and Ladakhi highlanders. High Alt Med Biol . 23:319-329, 2022. Background: Identifying a stable and reliable reference gene (RG) is a prerequisite for the unbiased and unambiguous analysis of gene expression data. It has become evident that conventionally used housekeeping genes such as beta-actin ( ACTB ), glyceraldehyde-3-phosphate dehydrogenase ( GAPDH ), and peptidylprolyl Isomerase A ( PPIA ) exhibit varied expression patterns under hypoxia. Hence, the identification of stable RGs for humans exposed to hypobaric hypoxia can enhance the accuracy of gene expression studies by limiting the negligent use of random housekeeping genes. Methods: Using TaqMan™ array-based quantitative real-time quantitative polymerase chain reaction, we evaluated the expression of 32 commonly used human RGs among lowlanders at Delhi (altitude 216 m, SL), lowlanders at Leh (altitude 3,524 m) after 1 day (HA-D1) and 7 days (HA-D7), as well as indigenous Ladakhi highlanders at the same altitude. The expression stability of the RGs was evaluated using geNorm, NormFinder, BestKeeper, Delta CT method, and RefFinder algorithms. Results: Our studies identify TATA-box binding protein ( TBP ), proteasome 26S subunit, ATPase 4 ( PSMC4 ), and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta ( YWHAZ ) as the most stable human RGs for normalizing human gene expression under hypobaric hypoxia. In addition, we report the combination of TBP and cyclin-dependent kinase inhibitor 1B ( CDKN1B ) as the most stable RG for studying lowlander gene expression during high-altitude exposure. In contrast, RPL30 and 18S exhibited maximum variation across study groups and were identified as the least stable RGs.

Background: The present study aimed to analyse the role of myokines and the regeneration capacity of skeletal muscle during chronic hypobaric hypoxia (CHH)., Methods: Male Sprague-Dawley rats were exposed to hypobaric hypoxia (HH) for 1d, 3d and 7d., Results: Exposure to HH enhanced the levels of decorin, irisin, IL-6 and IL-15 till 3 days of hypoxia and on 7 day of exposure, no significant changes were observed in relation to control. A significant upregulation in myostatin, activated protein kinase, SMAD3, SMAD4, FOXO-1, MURF-1 expression was observed with prolonged HH exposure as compared to normoxic control. Further, myogenesis-related markers, PAX-7, Cyclin D1 and myogenin were downregulated during CHH exposure in comparison to control. Energy metabolism regulators such as Sirtuin 1, proliferator-activated receptor gamma coactivator-1α and GLUT-4, were also increased on 1-d HH exposure that showed a declining trend on CHH exposure., Conclusions: These results indicated the impairment in the levels of myokines and myogenesis during prolonged hypoxia. CHH exposure enhanced the levels of myostatin and reduced the regeneration or repair capacity of the skeletal muscles. Myokine levels could be a predictive biomarker for evaluating skeletal muscle performance and loss at high altitudes.

A new efficient free radical scavenger HPN-C 6 prevented brain damage induced by hypobaric hypoxia via reducing oxidative damage and inhibiting apoptosis and inflammatory response in mice brain. [Display omitted] • The oxidant stress in mice brain induced by hypobaric hypoxia was inhibited by HPN-C 6. • HPN-C 6 increased the activities of antioxidant enzymes. • HPN-C 6 inhibited the occurrence of inflammatory reaction in mice brain. • HPN-C 6 suppressed the hypobaric hypoxia-induced apoptosis. Hypobaric hypoxia (HH) results in the increased formation of ROS and induces a wide range of deleterious effects on the brain. Nitronyl nitroxide radicals are a kind of stable organic nitroxide radicals with a good ability to scavenge ROS. Herein, a series of new nitronyl nitroxide radicals was synthesized according to the previous method. Among them, a compound with six carbon atoms alkyl chain (HPN-C 6) was screened for estimating the protective effect against HH-induced brain injury in the acute HH mouse model. The results showed that HPN-C 6 ameliorated oxidative stress by decreasing the activity of LDH and the content of H 2 O 2 , NO, and MDA, increasing the activities of SOD, CAT and GSH-PX in the brain tissue of HH injured mice. Moreover, HPN-C 6 exhibited an anti-inflammatory effect by reducing the level of IL-1β, TNF-α, and IL-6 in the brains of mice after HH exposure through regulating the P38 MAPK signaling pathway. In addition, HPN-C 6 exhibited the protection effect by inhibiting the release of mitochondrial cytochrome C , locking the activation of caspase-3, and downregulating the expression of Bax and upregulating the expression of Bcl-2. HPN-C 6 pretreatment could inhibit the caspase-dependent mitochondria apoptosis pathway. These findings indicate that HPN-C 6 is a potential therapeutic agent to prevent brain damage induced by HH. [ABSTRACT FROM AUTHOR]

Salidroside (Sal), an active ingredient from Rhodiola crenulate , has been reported to exert neuroprotection in cerebral injury from hypobaric hypoxia (HH) at high altitude. However, it remains to be understood whether its protective effects are related to inflammation suppression. In the present work, we aimed to reveal the mechanism of Sal attenuating HH-induced brain injury in mice caused by an animal hypobaric and hypoxic chamber. Our results provided that Sal could attenuate HH-evoked pathological injury and oxidative stress response by decreasing the content of ROS and MDA, and elevating the activities of SOD and GSH-Px. Sal treatment could partly enhance the energy metabolism, evidenced by increasing the activities of Na+-K+-ATPase, Ca2+-Mg2+-ATPase, ATP, SDH, HK and PK, while decreasing the release of LDH and LD. Meanwhile, Sal administration reversed the degradation of tight junction proteins ZO-1, Occludin and Claudin-5. Further, the increased levels of TNF-α, IL-1β and IL-6 were confined with Sal administration under the HH condition. Importantly, Sal could downregulate the proteins expression of p–NF–κB-p65, NLRP3, cleaved-Caspase-1 and ASC. Sal also decreased the protein expression of iNOS and COX2 with the increased CD206 and Arg1 expression. Taken together, these data provided that the inhibited NF-κB/NLRP3 pathway by Sal could attenuate HH-induced cerebral oxidative stress injury, inflammatory responses and the blood brain barrier (BBB) damage, attributing to the improved energy metabolism and the microglial phenotype of anti-inflammatory M2. The findings suggested that Sal was expected to be a promising anti-inflammatory agent for high altitude HH-induced brain injury. [ABSTRACT FROM AUTHOR]

Hypobaric hypoxia exposure leads to brain edema, followed by neuropsychological disorders. However, the related mechanism and effective treatments are still unclear. The study aimed to discuss the neuroprotective effects of Cordycepin on hypobaric hypoxia-induced cognitive impairment. The study contained two parts. In the first part, rats underwent hypobaric hypoxia (HH) exposure for 7 days, with or without Cordycepin (10 mg/kg) or lipopolysaccharide (LPS,10 mg/kg) treatment once a day. In the second part, rats underwent HH exposure for 7 days, with or without TAK242 (3 mg/kg) and Cordycepin (10 mg/kg) once a day. Open field and Morris water maze test were performed one day after the 7days treatment. The BBB permeability was detected by the uptake of NaF. Western bloting was used to detect the levels of TLR4/MyD88/NF-κB pathway related proteins in the hippocampus. The hippocampal and serous levels of cytokines were detected by ELISA. The structure of tight junctions in the hippocampus was observed under the transmission electron microscopy. Both acute HH and LPS exposure could activate the TLR4 pathway and neuroinflammation, further induced BBB disruption and cognitive injury. Cordycepin could inhibit the activation of theTLR-4/NF-κB/MMP-9 pathway, which further attenuated cognitive dysfunction, and disruption of the blood-brain barrier (BBB) in HH and LPS exposed rats. Furthermore, TAK242, a TLR4 antagonist, also inhibited the activation of theTLR-4/NF-κB/MMP-9 pathway and BBB disruption, as well as attenuated HH induced cognitive impairment. Cordycepin could ameliorate HH-induced neuroinflammation, BBB disruption, and cognitive damage partly by inhibiting the TLR-4/NF-κB/MMP-9 pathway. [ABSTRACT FROM AUTHOR]

Purpose: Dihydromyricetin (DHM) is the major bioactive constituent of rattan tea. Our aim was to investigate the possible mechanism and the effect of DHM in counteracting hypobaric hypoxia (HH)-induced exercise intolerance. Methods: Male Sprague-Dawley rats were pretreated with three doses of DHM (50, 75, and 100 mg•kg-1) for 7 d and subjected to simulated high-altitude conditions (5000 m with 10.9% oxygen). Physical performance was assessed with the run-to-fatigue model. Mitochondrial morphology in the gastrocnemius muscle was observed by transmission electron microscopy. Protein expression was detected by western blotting. The activity of mitochondrial electron transport chain was analyzed by enzyme-linked immunosorbent assay. Results: DHM administration prolonged the run-to-fatigue time in a dose-dependent manner compared with the control (22.9 ± 2.2, 46.1 ± 4.4, 61.3 + 3.1 vs 18.4 ± 1.7 min, which represented 50, 75, 100 mg•kg-1, and the control groups, respectively). DHM also reduced serum blood urea nitrogen, lactate dehydrogenase, and creatine kinase activity levels. HH-induced mitochondrial injuries, including morphological changes, reduction in mitochondrial density and mitochondrial DNA content, and decrease in respiratory chain complex (I, II, IV, and V) activities were effectively attenuated by DHM. Protein expression of mitochondrial biogenesis markers, including peroxisome proliferator-activated receptor-γ coactivator lα, sirtuin 1, nuclear respiratory factor 1, mitochondrial transcription factor A, AMP-activated protein kinase, and AMP-activated protein kinase phosphorylation, was significantly downregulated in HH, whereas DHM pretreatment significantly restored expression levels. DHM also modulated mitochondrial dynamics of fusion and fission by increasing mitofusins 1 and 2, while decreasing fission-related, dynamin-related protein 1 and mitochondrial fission 1. Conclusions: DHM improves physical performance under simulated high-altitude conditions via protecting mitochondrial biogenesis and modulating mitochondrial dynamics in skeletal muscle cells. [ABSTRACT FROM AUTHOR]

Hypobaric hypoxia (HH) induces oxidative stress (OS) and is associated with the generation of reactive oxygen species (ROS). Vitamin C is an efficient antioxidant, and it is used in a high-altitude environment to reduce the OS. The present study explores the role of vitamin C on some HH-induced changes of immune parameters in rats which were exposed to HHc condition at 18,000 ft in a simulated chamber for 8 h/day for 6 days with and without vitamin C administration at three different doses (200, 400, and 600 mg/kg body wt). The phagocytic activity of circulating blood WBC was increased, and the cytotoxic activity of splenic mononuclear cell (MNC) and the delayed type of hypersensitivity (DTH) responses to bovine serum albumin (BSA) were decreased in rats exposed to HHc condition, but these immune changes were blocked after administration of vitamin C at 400 mg/kg body wt. The leukocyte adhesive inhibition index (LAI) was not altered either in HHc condition or after administration of vitamin C in HHc condition. The serum corticosterone (CORT) concentration was increased in rats exposed to HHc condition which was blocked after administration of vitamin C (400 mg/kg body wt). The immune parameters and serum CORT concentration, however, did not show any recovery after administration of vitamin C at the dose of 200 and 600 mg/kg body wt. The present study indicates that administration of vitamin C at a dose of 400 mg/kg body wt may prevent the HH-induced immunological changes but not at the lower dose (200 mg/kg body wt) or higher dose (600 mg/kg body wt) in rats. [ABSTRACT FROM AUTHOR]

Oxygen-sensing mechanisms have evolved to maintain cell and tissue homeostasis since the ability to sense and respond to changes in oxygen is essential for survival. The primary site of oxygen sensing occurs at the level of the carotid body which in response to hypoxia signals increased ventilation without the need for new protein synthesis. Chronic hypoxia activates cellular sensing mechanisms which lead to protein synthesis designed to alter cellular metabolism so cells can adapt to the low oxygen environment without suffering toxicity. The master regulator of the cellular response is hypoxia-inducible factor (HIF). Activation of this system under condition of hypobaric hypoxia leads to weight loss accompanied by increased basal metabolic rate and suppression of appetite. These effects are dose dependent, gender and genetic specific, and results in adverse effects if the exposure is extreme. Hypoxic adipose tissue may represent a unified cellular mechanism for variety of metabolic disorders, and insulin resistance in patients with metabolic syndrome. [ABSTRACT FROM AUTHOR]

Acute hypobaric hypoxia may damage brain and lung tissues due to the development of disorders such as High Altitude Cerebral Edema (HACE) and High Altitude Pulmonary Edema (HAPE). Rats, like humans, exhibit susceptibility and tolerance in the same population to such extreme conditions. We selected reference genes to normalize the qRTPCR study in order to evaluate whether a change in expression of Hif1á and Hif2á occurs in lungs of such rats exposed to acute hypobaric hypoxia.The hypobaric hypoxia susceptible (HHS) and tolerant (HHT) Sprague-Dawley rat groups, formed on the basis of their gasping time, were exposed to a simulated altitude of 9144 m at 24oC in a decompression chamber for a short duration of one hour. A set of reference genes including Gapdh, Actb, Rpl11, Rpl10a, Rps15 and Ppia was examined for normalization in qRT-PCR study to analyze expression of target genes Hif1á and Hif2á in the lungs of these groups as compared to the normoxic control. Rpl11, Actb and Rps15 genes in combination represented the most suitable reference genes based upon GeNorm, NormFinder and BestKeeper analyses. Expression of Hif1á and Hif2á genes was reduced in both HHS and HHT rat lungs. However, enhanced protein expression of HIF-1 in HHS group, and weak expression of HIF-2 protein in both groups was recorded. Our findings suggest that HIF-1 may play a significant role in mediating early responses towards acute hypobaric hypoxia in lung samples of HHS as well as HHT rats, with its profound protein expression in the former. [ABSTRACT FROM AUTHOR]

Background. The antioxidant effects of lycopene, evidenced in vitro and in vivo under pathological conditions, led us to study in an experimental model of complex combined stress (exposure to moderate hypobaric hypoxia and ozone, and physical exercise) the acute changes in the tissue oxidant/antioxidant (O/AO) balance following lycopene supplementation. Aims. The influence of acute exposure to hypobaric hypoxia and ozone and of lycopene supplementation on tissue redox homeostasis under physical exercise conditions was studied in the myocardium. Methods. The research was performed in 6 groups of white male Wistar rats: group I - control group, sedentary rats under normoxia conditions; group II - sedentary rats exposed to combined acute stress: hypobaric hypoxia (corresponding to a 2500 m altitude) and O3; group III - animals exposed to combined acute stress - moderate hypoxia + O3 - followed by exercise, under normoxia conditions; group IV - sedentary rats under normoxia conditions, with lycopene administration; group V - animals exposed to combined acute stress - moderate hypoxia + O3 - followed by lycopene administration; group VI - animals exposed to combined acute stress - moderate hypoxia + O3 - followed by lycopene administration and daily exercise, under normoxia conditions. Exposure was simulated in the hypobaric chamber for 3 days, 20 hours a day, at 2500 m. Groups III and VI were trained daily for 3 days under normoxia conditions, using the swimming test. Groups IV, V and VI received 0.0375 mg/kg body weight lycopene by oral gavage (before exercise for group VI), daily. In order to measure the indicators of the oxidant/ antioxidant (O/AO) balance, tissue samples were collected from the myocardium. On day 3, the following were determined: malondialdehyde (MDA), protein carbonyls (PC), hydrogen donor capacity (HD) and total sulfhydryl (SH) groups. Results. Our experimental results obtained in animals that were exercise trained for 3 days and subjected to combined acute stress - hypobaric hypoxia and O3 - and lycopene administration, support the favorable effects of lycopene as an effective antioxidant in the myocardium under exercise conditions. Conclusions. Lycopene administration in animals subjected to combined acute stress - hypobaric hypoxia and O3 - followed by exercise determines an increase in oxidative stress (OS) on account of MDA and PC in the myocardium, compared to control animals. [ABSTRACT FROM AUTHOR]

Feuerecker, Matthias, Brian Crucian, Alex P. Salam, Ales Rybka, Ines Kaufmann, Marjan Moreels, Roel Quintens, Gustav Schelling, Manfred Thiel, Sarah Baatout, Clarence Sams, and Alexander Choukèr. Early adaption in the Antarctic environment at Dome C: Consequences on stress-sensitive innate immune functions. High Alt Med Biol 15:341-348, 2014.- Purpose/Aims: Medical reports of Antarctic expeditions indicate that health is affected under these extreme conditions. The present study at CONCORDIA-Station (Dome C, 3233 m) seeks to investigate the early consequences of confinement and hypobaric hypoxia on the human organism. Methods: Nine healthy male participants were included in this study. Data collection occurred before traveling to Antarctica (baseline), and at 1 week and 1 month upon arrival. Investigated parameters included basic physiological variables, psychological stress tests, cell blood count, stress hormones, and markers of innate immune functions in resting and stimulated immune cells. By testing for the hydrogen peroxide (H2O2) production of stimulated polymorphonuclear leukocytes (PMNs), the effects of the hypoxia-adenosine-sensitive immune modulatory pathways were examined. Results: As compared to baseline data, reduced oxygen saturation, hemoconcentration, and an increase of secreted catecholamines was observed, whereas no psychological stress was seen. Upon stimulation, the activity of PMNs and L-selectin shedding was mitigated after 1 week. Endogenous adenosine concentration was elevated during the early phase. In summary, living conditions at high altitude influence the innate immune system's response. After 1 month, some of the early effects on the human organism were restored. Conclusion: As this early adaptation is not related to psychological stress, the changes observed are likely to be induced by environmental stressors, especially hypoxia. As hypoxia is triggering ATP-catabolism, leading to elevated endogenous adenosine concentrations, this and the increased catecholamine concentration might contribute to the early, but reversible downregulation of innate immune functions. This indicates the slope of innate immune adaptation to hypoxia. [ABSTRACT FROM AUTHOR]

Chen, Chung-Yu, Chien-Wen Hou, Jeffrey R. Bernard, Chiu-Chou Chen, Ta-Cheng Hung, Lu-Ling Cheng, Yi-Hung Liao, and Chia-Hua Kuo. Rhodiola crenulata- and Cordyceps sinensis-based supplement boosts aerobic exercise performance after short-term high altitude training. High Alt Med Biol 15:371-379, 2014.-High altitude training is a widely used strategy for improving aerobic exercise performance. Both Rhodiola crenulata (R) and Cordyceps sinensis (C) supplements have been reported to improve exercise performance. However, it is not clear whether the provision of R and C during high altitude training could further enhance aerobic endurance capacity. In this study, we examined the effect of R and C based supplementation on aerobic exercise capacity following 2-week high altitude training. Alterations to autonomic nervous system activity, circulatory hormonal, and hematological profiles were investigated. Eighteen male subjects were divided into two groups: Placebo ( n=9) and R/C supplementation (RC, n=9). Both groups received either RC (R: 1400 mg+C: 600 mg per day) or the placebo during a 2-week training period at an altitude of 2200 m. After 2 weeks of altitude training, compared with Placebo group, the exhaustive run time was markedly longer (Placebo: +2.2% vs. RC: +5.7%; p<0.05) and the decline of parasympathetic (PNS) activity was significantly prevented in RC group (Placebo: −51% vs. RC: −41%; p<0.05). Red blood cell, hematocrit, and hemoglobin levels were elevated in both groups to a comparable extent after high altitude training ( p<0.05), whereas the erythropoietin (EPO) level remained higher in the Placebo group (∼48% above RC values; p<0.05). The provision of an RC supplement during altitude training provides greater training benefits in improving aerobic performance. This beneficial effect of RC treatment may result from better maintenance of PNS activity and accelerated physiological adaptations during high altitude training. [ABSTRACT FROM AUTHOR]

Rubenstein, David A, and Wei Yin. Hypergravity and hypobaric hypoxic conditions promote endothelial cell and platelet activation. High Alt Med Biol 15:396-405, 2014.-Cardiovascular disease risk is heightened during exposure to altered gravity and/or altered barometric conditions. Previous work has suggested that this heightened cardiovascular risk is due to enhancements of endothelial cell inflammatory and/or thrombogenic responses. In recent work, the role of platelets on instigating or inhibiting endothelial cell responses associated with cardiovascular disease has been found to be dependent on both biochemical and biophysical factors. In this work, we aimed to determine how two biophysical forces, gravity and atmospheric pressure, alter endothelial cell and platelet functions and their interactions to instigate or inhibit cardiovascular disease responses. To address this aim, endothelial cells and platelets were subjected to a force 8 times greater than the normal gravitational force, for up to 30 minutes. In separate experiments, endothelial cells and platelets were subjected to 50% of normal atmospheric pressure. Endothelial cell and platelet responses, associated with cardiovascular diseases, were measured as a time course during exposure. In general, the exposure of endothelial cells to either hypergravity or hypobaric conditions enhanced cardiovascular disease responses. However, the presence of platelets generally inhibited endothelial cell responses. Platelet activation was, however, somewhat enhanced under both hypergravity and hypobaric conditions. Our data suggest that altered biophysical forces can modulate endothelial cell and platelet responses that are salient for cardiovascular disease progression. However, the interaction of these two cells tends to restrain the progression of the pro-cardiovascular disease responses. [ABSTRACT FROM AUTHOR]

Intermittent hypobaric hypoxia (IHH) induced a decrease in sperm count and oxidative damage in epididymis. We have previously demonstrated that a blueberry- enriched polyphenol extract (BB-4) reduced the adverse effects of oxidative stress in rat testis under hypobaric hypoxia. The aim of this study was to evaluate whether BB-4 could reverse oxidative stress in epididymis. To evaluate the protective role of BB-4 in epididymis, male rats were exposed to IHH. Lipid peroxidation, (LPO) expression and activity of glutathione reductase (GR) were evaluated. Our results showed a reduction in LPO and a decrease in GR activity in rat epididymis exposed to IHH. These results suggest that BB-4 can prevent the effects of IHH in rat epididymis. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Ascent to high altitude may result in a hypobaric hypoxic brain injury. The development of acute mountain sickness (AMS) is considered a multifactorial process with hypoxia-induced blood-brain barrier (BBB) dysfunction and resultant vasogenic oedema cited as one potential mechanism. Peripheral S100B is considered a biomarker of BBB dysfunction. This study aims to investigate the S100B release profile secondary to hypoxic brain injury and comment on BBB disturbance and AMS. METHODS: A prospective field study of 12 subjects who ascended Mt Fuji (3700 m) was undertaken. RESULTS: The mean baseline plasma S100B level was 0.11 μg/l (95% CI 0.09-0.12), which increased to 0.22 μg/l (95% CI 0.17-0.27) at the average of three high altitude levels (2590, 3700, and 2590 m on descent) (P<=03.3). The mean level for the seven subjects who experienced AMS rose from 0.10 to 0.19 μg/l compared to 0.12 to 0.25 μg/l for the five subjects who did not develop AMS (P<=03.3). [ABSTRACT FROM AUTHOR]

Background. Schizophrenia is a serious psychiatric disorder with 0.5-1% prevalence worldwide. Administration of MK- 801 and exposure to intermittent hypobaric hypoxia were experimentally used to establish schizophrenia models in rats. Aims. We aimed to study experimentally in male and female rats the following: the postnatal induced schizophrenia model by MK-801 administration and intermittent hypobaric hypoxia exposure during postnatal days 7-21; the changes in motor and emotional behaviour in rats with schizophrenia, and the gender differences between male and female rats. Methods. The research was performed in 6 groups of rats (n=10 animals/group) as follows: group I - male, control; group II - female, control; group III - male with schizophrenia induced by MK-801 administration; group IV - male with schizophrenia induced through intermittent hypobaric hypoxia exposure; group I - female with schizophrenia induced by MK-801 administration; group IV - female with schizophrenia induced through intermittent hypobaric hypoxia exposure. Involuntary motility and emotional behaviour were tested using the Open Field test. The examination moments were postnatal days 22 (T0) and 49 (T28). Results. The Open Field test values - emotional score, evidenced very statistically significant differences between all groups (III-VI) with schizophrenia, compared to controls (I-II) at moment T28. The Open Field test values - motility score, evidenced very statistically significant differences between all groups (III-VI) with schizophrenia, compared to controls (I-II) at moment T28. The emotional score and the motility score showed statistically significant differences between the male and female group (III, V) in rats with schizophrenia induced by MK-801 administration, compared to initial values. Conclusions. Emotional behaviour increases in male and female rats with schizophrenia, compared to controls. Involuntary motor behaviour decreases in male and female rats with schizophrenia, compared to controls. We did not observe a significant gender difference. [ABSTRACT FROM AUTHOR]

Hippocampal gluco- and mineralocorticoid receptors (GR, MR) have important roles in the mechanisms regulating the activity of the hypothalamo-hypophyseal-adrenocortical system (HHAS), neuron survival/death, learning, and memory. Imbalance in MR and GR contents lead to impairments of HHAS activity and can promote neuron damage/death in extreme conditions. The present study used a quantitative immunocytochemistry method to provide the first comparative analysis of the effects of different regimes of hypobaric hypoxia on the nature of GR and MR expression in the dorsal (CA1) and ventral (dentate gyrus) parts of the hippocampus in rats. The data obtained here showed that severely harmful hypoxia induces marked impairments to the expression of both GR and MR in CA1 and dental gyrus cells, which correlated with damage/death of a significant proportion of neurons in CA1 and dysregulation of the activity of the HHAS. Series of three and six sessions (but not one session) of preconditioning with moderate hypoxia preceding severe hypoxia prevented these impairments. [ABSTRACT FROM AUTHOR]

Preconditioning with repetitive mild hypobaric hypoxia is known to increase tolerance of susceptible brain neurons to severe hypoxia, whereas a single trial of mild hypoxia has been ineffective. In the present study, the effects of three-trial and one-trial hypobaric preconditioning on the expression of the protective transcription factor phosphorylated CREB (pCREB) and neurotrophin BDNF, before and after severe hypobaric hypoxia, have been comparatively studied in the neocortex of rats. As revealed by quantitative immunocytochemistry, the severe hypobaric hypoxia (180Torr, 3h) substantially down-regulated the levels of pCREB and BDNF in cortical neurons assessed 24h after the treatment. One trial of mild hypoxia (360Torr, 2h) also reduced by half the number of BDNF-expressing cells, but had no effect on pCREB expression in the neocortex. In contrast, the exposure to three trials of mild hypoxia at 24h intervals considerably up-regulated pCREB and BDNF levels in the neocortex of rats. Only preconditioning by three trials of mild hypoxia (360Torr, 2h, 24h intervals), but not a single trial preconditioning, was neuroprotective significantly enhancing the pCREB and BDNF neuronal expression in response to severe hypoxic challenge. The results of the present study indicate that development of the neuronal hypoxic tolerance induced by the three-trial mild hypoxic preconditioning is apparently associated with activation of CREB and BDNF expression. [ABSTRACT FROM AUTHOR]

Purpose: Commercial parabolic flights accessible to customers with a wide range of health states will become more prevalent in the near future because of a growing private space flight sector. However, parabolic flights present the passengers' cardiovascular system with a combination of stressors, including a moderately hypobaric hypoxic ambient environment (HH) and repeated gravity transitions (GT). Thus, the aim of this study was to identify unique and combined effects of HH and GT on the human cardiovascular, pulmonary and fluid regulation systems. Methods: Cardiac index was determined by inert gas rebreathing (CI), and continuous non-invasive finger blood pressure (FBP) was repeatedly measured in 18 healthy subjects in the standing position while they were in parabolic flight at 0 and 1.8 G. Plasma volume (PV) and fluid regulating blood hormones were determined five times over the flight day. Eleven out of the 18 subjects were subjected to an identical test protocol in a hypobaric chamber in ambient conditions comparable to parabolic flight. Results: CI in 0 G decreased significantly during flight (early, 5.139 ± 1.326 L/min; late, 4.150 ± 1.082 L/min) because of a significant decrease in heart rate (HR) (early, 92 ± 15 min; late, 78 ± 12 min), even though the stroke volume (SV) remained the same. HH produced a small decrease in the PV, both in the hypobaric chamber and in parabolic flight, indicating a dominating HH effect without a significant effect of GT on PV (−52 ± 34 and −115 ± 32 ml, respectively). Pulmonary tissue volume decreased in the HH conditions because of hypoxic pulmonary vasoconstriction (0.694 ± 0.185 and 0.560 ± 0.207 ml) but increased at 0 and 1.8 G in parabolic flight (0.593 ± 0.181 and 0.885 ± 0.458 ml, respectively), indicating that cardiac output and arterial blood pressure rather than HH are the main factors affecting pulmonary vascular regulation in parabolic flight. Conclusion: HH and GT each lead to specific responses of the cardiovascular system in parabolic flight. Whereas HH seems to be mainly responsible for the PV decrease in flight, GT overrides the hypoxic pulmonary vasoconstriction induced by HH. This finding indicates the need for careful and individual medical examination and, if necessary, health status improvement for each individual considering a parabolic flight, given the effects of the combination of HH and GT in flight. [ABSTRACT FROM AUTHOR]

Travel to high altitude exposes the human body to a variety of stresses, the most prominent being reduced available oxygen with increase in altitude due to reduced partial pressure of oxygen. Several physiological responses are initiated in the human body to promote faster acclimatization to these adverse environmental conditions. These physiological and molecular readjustments encompassing acclimatization, namely, hypoxic ventilatory response, diuresis, increased cardiac output, improved oxygen carrying capacity and cerebral blood flow, Hypoxia inducible factor 1 stabilization, etc., converge to a single outcome, ensuring optimal bioavailability of oxygen. In this article, we describe the basic acclimatization framework mentioned above. [ABSTRACT FROM AUTHOR]

Highlights: [•] Increased depression and suicide rates are associated with life at higher altitudes. [•] Rats were housed for one week at 10,000ft of simulated altitude. [•] Animals were tested with the forced swim test and magnetic resonance spectroscopy. [•] Hypoxia-treated rats had augmented depression-like behavior in the forced swim test. [•] Neurochemical alterations after hypobaric hypoxia were found in frontal cortex voxel. [Copyright &y& Elsevier]

Engan, Harald K, Angelica Lodin-Sundstrom, Fanny Schagatay, and Erika Schagatay. The effect of climbin Mount Everest on spleen contraction and increase in hemoglobin concentration during breath holding and exercise. High Alt Med Biol. 15:52-57, 2014.-Release of stored red blood cells resulting from spleen contraction improves human performance in various hypoxic situations. This study determined spleen volume resulting from two contraction-evoking stimuli: breath holding and exercise before and after altitude acclimatization during a Mount Everest ascent (8848 m). Eight climbers performed the following protocol before and after the climb: 5 min ambient air respiration at 1370 m during rest, 20 min oxygen respiration, 20 min ambient air respiration at 1370 m, three maximal-effort breath holds spaced by 2 min, 10 min ambient air respiration, 5 min of cycling at 100 W, and finally 10 min ambient air respiration. We measured spleen volume by ultrasound and capillary hemoglobin (HB) concentration after each exposure, and heart rate (HR) and arterial oxygen saturation (Sa o2) continuously. Mean (SD) baseline spleen volume was unchanged at 213 (101) mL before and 206 (52) mL after the climb. Before the climb, spleen volume was reduced to 184 (83) mL after three breath holds, and after the climb three breath holds resulted in a spleen volume of 132 (26) mL ( p=0.032). After exercise, the preclimb spleen volume was 186 (89) mL vs. 112 (389) mL) after the climb ( p=0.003). Breath hold duration and cardiovascular responses were unchanged after the climb. We concluded that spleen contraction may be enhanced by altitude acclimatization, probably reflecting both the acclimatization to chronic hypoxic exposure and acute hypoxia during physical work. [ABSTRACT FROM AUTHOR]

Highlights: [•] We examined the impact of high altitude on blue cone function. [•] Blue cone function was examined objectively using electroretinography. [•] At 4559m an attenuation of blue cone function was observed. [•] Functional impairment was not associated with symptoms of acute mountain sickness. [•] First report of blue cone ERG at high altitude. [ABSTRACT FROM AUTHOR]

Copyright of Studia Universitatis Babes-Bolyai, Educatio Artis Gymnasticae is the property of Babes-Bolyai University, Cluj-Napoca, Romania and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Travel is more affordable and improved high-altitude airports, railways, and roads allow rapid access to altitude destinations without acclimatization. The physiology of exposure to altitude has been extensively described in healthy individuals; however, there is a paucity of data pertaining to those who have reduced reserve. This Physiology in Medicine article discusses the physiological considerations relevant to the safe travel to altitude and by commercial aircraft in patients with pulmonary and/or cardiac disease. [ABSTRACT FROM AUTHOR]