Effects of space flight on surface marker expression.

Space flight has been shown to affect expression of several cell surface markers. These markers play important roles in regulation of immune responses, including CD4 and CD8. The studies have involved flight of experimental animals and humans followed by analysis of tissue samples (blood in humans, rats and monkeys, spleen, thymus, lymph nodes and bone marrow in rodents). The degree and direction of the changes induced by space flight have been determined by the conditions of the flight. Also, there may be compartmentalization of the response of surface markers to space flight, with differences in the response of cells isolated from blood and local immune tissue. The same type of compartmentalization was also observed with cell adhesion molecules (integrins). In this case, the expression of integrins from lymph node cells differed from that of splenocytes isolated from rats immediately after space flight. Cell culture studies have indicated that there may be an inhibition in conversion of a precursor cell line to cells exhibiting mature macrophage characteristics after space flight, however, these experiments were limited as a result of technical difficulties. In general, it is clear that space flight results in alterations of cell surface markers. The biological significance of these changes remains to be established.     

Space flight, microgravity, stress, and immune responses.

Exposure of animals and humans to space flight conditions has resulted in numerous alterations in immunological parameters. Decreases in lymphocyte blastogenesis, cytokine production, and natural killer cell activity have all been reported after space flight. Alterations in leukocyte subset distribution have also been reported after flight of humans and animals in space. The relative contribution of microgravity conditions and stress to the observed results has not been established. Antiorthostatic, hypokinetic, hypodynamic, suspension of rodents and chronic head-down tilt bed-rest of humans have been used to model effects of microgravity on immune responses. After use of these models, some effects of space flight on immune responses, such as decreases in cytokine function, were observed, but others, such as alterations in leukocyte subset distribution, were not observed. These results suggest that stresses that occur during space flight could combine with microgravity conditions in inducing the changes seen in immune responses after space flight. The biological/biomedical significance of space flight induced changes in immune parameters remains to be established. Grant Numbers: NCC2-859, NAG2-933.     

The response of endocrine system to stress loads during space flight in human subject.

The responses of endocrine system to the exposure to stress-work load and hormonal changes during oral glucose tolerance tests were studied in the Slovak astronaut before (three weeks before flight), during (on the 4th and the 6th days of space flight), and after space flight (1-3 days and 15-17 days after space flight) on board of space station MIR. Blood samples during the tests were collected via cannula inserted into cubital vein, centrifuged in the special appliance Plasma-03, frozen in Kryogem-03, and at the end of the 8-day space flight transferred to Earth in special container for hormonal analysis. Preflight workload produced an increase of plasma norepinephrine and a moderate elevation of epinephrine levels. Plasma levels of insulin, growth hormone, prolactin and cortisol were not markedly changed immediately or 10 min after the end of work load. The higher increases of plasma growth hormone, prolactin and catecholamine levels were noted after workload during space flight as compared to preflight response. The higher plasma glucose and insulin levels were noted during the oral glucose tolerance test in space flight and also in the post flight period. Plasma epinephrine levels were slightly decreasing during glucose tolerance test; however, plasma norepinephrine levels were not changed. The similar patterns of catecholamine levels during glucose tolerance test were found when compared the preflight, in-flight and post flight values. These data demonstrate the changes of the dynamic responses of endocrine system to stress-work and metabolic loads during space flight in human subject.     

Changes in the central nervous system during long-duration space flight: implications for neuro-imaging.

The purpose of this paper is to review the potential functional and morphological effects of long duration space flight on the human central nervous system (CNS) and how current neuroimaging techniques may be utilized to study these effects. It must be determined if there will be any detrimental changes to the CNS from long term exposure to the space environment if human beings are to plan interplanetary missions or establish permanent space habitats. Research to date has focused primarily on the short term changes in the CNS as the result of space flight. The space environment has many factors such as weightlessness, electromagnetic fields, and radiation, that may impact upon the function and structure of the CNS. CNS changes known to occur during and after long term space flight include neurovestibular disturbances, cephalic fluid shifts, alterations in sensory perception, changes in proprioception, psychological disturbances, and cognitive changes. Animal studies have shown altered plasticity of the neural cytoarchitecture, decreased neuronal metabolism in the hypothalamus, and changes in neurotransmitter concentrations. Recent progress in the ability to study brain morphology, cerebral metabolism, and neurochemistry in vivo in the human brain would provide ample opportunity to investigate many of the changes that occur in the CNS as a result of space flight. These methods include positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI).     

Simulation analysis for effects of bone loss on acceleration tolerance of human lumbar vertebra

The purpose of the present study was to analyze and predict the changes in acceleration tolerance of human vertebra as a result of bone loss caused by long-term space flight. A human L3–L4 vertebra FEM model was constructed, in which the cancellous bone was separated, and surrounding ligaments were also taken into account. The simulation results demonstrated that bone loss has more of an effect on the acceleration tolerance in x-direction. The results serve to aid in the creation of new acceleration tolerance standards, ensuring astronauts return home safely after long-term space flight. This study shows that more attention should be focused on the bone degradation of crew members and to create new protective designs for space capsules in the future.     

Summing-up cosmonaut participation in long-term space flights.

The health condition and work capacity of space travellers during many flights remained adequate. Medical examinations performed during and after space flights consistently revealed the following symptom-complexes: space motion sickness, changes in the muscles system, hemodynamics, fluid-electrolyte balance and its regulation, calcium metabolism and bone density, transient erythrocytopenia and immunity decline. This paper presents a detailed discussion of the changes observed in space flight.     

空间小鼠实验有效载荷研究进展

啮齿动物是空间研究中常见的模型对象,已开展的空间生物实验中,小鼠表现出对飞行条件的有效适应.通过空间培养,研究者可对失重环境下小鼠的生理行为、骨骼和神经系统变化做进一步研究分析.本文对空间小鼠实验有效载荷的研究进展及其空间飞行实验进行了概述,为中国空间站上的小鼠培养箱设计提供参考.概述了地面小鼠培养技术和装置,为空间小...     

Leaf proteomic analysis of three rice heritable mutants after seed space flight

To explore the proteomic changes of heritable variant rice plants induced by space environment, three mutants were selected after seed space flight by comparing the phenotypes with their on-ground controls. R955 grew more tillers and became dwarf, 971-5 acquired higher grain yield and better stress resistance, 974-5 matured earlier. Leaf proteins were extracted during the tiller development and analyzed by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). More than 300 proteins were detected as reproducible Coomassie Brilliant Blue stained spots with pI values from around 4.0 to 7.0. Five proteins that changed significantly over the controls were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). The main functions of these proteins were photosynthesis, stress defense and metabolism including RuBisCO activase, glycine rich RNA binding protein, peroxidase, triosephosphate isomerase and phosphoenolpyruvate carboxylase, which might be probably associated with the altered phenotypes. Quantitative analyses were also applied: less total protein spots and more down-regulated protein spots were detected in the mutants, indicating there might be a major loss of protein in heritable variant rice plants after seed space flight. These results may provide new insights to understand the biological effects of space environment to rice.     

Metabolic energy required for flight.

This paper reviews data available from U.S. and U.S.S.R. studies on energy metabolism in the microgravity of space flight. Energy utilization and energy availability in space seem to be similar to those on Earth. However, negative nitrogen balances in space in the presence of adequate energy and protein intakes and in-flight exercise, suggest that lean body mass decreases in space. Metabolic studies during simulated (bed rest) and actual microgravity have shown changes in blood glucose, fatty acids, and insulin levels, suggesting that energy metabolism may be altered during flight. Future research should focus on the interactions of lean body mass, diet, and exercise in space and their roles in energy metabolism during space flight.     

The effect of artificial gravity on plasma and tissue lipids in rats: The Cosmos 936 experiment

Plasma and tissue lipids in male SPF Wistar rats flown for 18.5 days aboard the Cosmos 936 biosatellite were analyzed. One group of rats was subjected to artificial gravity by use of a centrifuge during the flight. An experiment simulating known space flight factors other than weightlessness was done on Earth. An increase of total cholesterol in plasma, of nonesterified fatty acids in plasma and brown adipose tissue, of triacylglycerols in plasma, liver, thymus and bone marrow was noted several hours after biosatellite landing. Smaller changes were observed in the terrestrial control experiment. With the exception of triacylglycerol accumulation in bone marrow, these increases disappeared 25 days after biosatellite landing. Exposing the rats aboard the biosatellite to artificial gravity was beneficial in the sense that such exposure inhibited the phospholipid and triacylglycerol increase in plasma and inhibited the increase of triacylglycerol in liver and especially in bone marrow.     

Properties of electrophoretic fractions of human embryonic kidney cells separated on Space Shuttle flight STS-8.

Suspensions of cultured primary human embryonic kidney cells were subjected to continuous flow electrophoresis on Space Shuttle flight STS-8. The objectives of the experiments were to obtain electrophoretically separated fractions of the original cell populations and to test these fractions for the amount and kind of urokinase (a kidney plasminogen activator that is used medically for digesting blood clots), the morphologies of cells in the individual fractions, and their cellular electrophoretic mobilities after separation and subsequent proliferation. Individual fractions were successfully cultured after return from orbit, and they were found to differ substantially from one another and from the starting sample with respect to all of these properties.     

Blood and clonogenic hemopoietic cells of newts after the space flight.

Ribbed newts were used for studying the effect of space flight on board of the biosatellite (Cosmos-2229) on blood and clonogenic hemopoietic cells. In blood of newts of the flight group, the relative proportion of neutrophils increased, whereas that of lymphocytes and eosinophils decreased. Space flight did not result in loss of the ability of newt blood cells to incorporate H3-thymidine. Analysis of clonogenic hemopoietic cells was performed using the method of hemopoietic colony formation on cellulose acetate membranes implanted into the peritoneal cavity of irradiated newts. To analyze reconstitution of hemopoiesis after irradiation donor hemopoietic cells from flight or control newts were transplanted into irradiated newts whose hemopoietic organs were investigated. The newt can be considered an adequate model for studying hemopoiesis under the conditions of the space flight.     

Activity of the sympathetic-adrenomedullary system in rats after space flight on the COSMOS biosatellites

The indicators of adrenomedullary activity (catecholamine content (CA) and the activity of the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and dopamine-β-hydroxylase (DBH)) were measured in the adrenal glands of rats living in a state of weightlessness for 18.5–19.5 days on board the biosatellites COSMOS 936 and COSMOS 1129. None of these indicators was significantly changed by space flight, neither in the group living in a state of weightlessness nor in the group living in a centrifuge on board the spacecraft and exposed to artificial gravity of 1 g (COSMOS 936). Animals exposed after space flight to repeated immobilization stress on Earth showed a significant decrease of adrenal adrenaline and an appreciable increase in adrenal TH activity compared to stressed animals which were not in space. These results suggest that a prolonged state of weightlessness during space flight does not by itself represent an intensive stressful stimulus for the adrenomedullary system but potentiates the response of cosmonauts to stress after return to Earth.     

An Outline of Investigation of Space Medicine Problem and Its Mechanism

The human exploration of space is one of the great voyages of discovery in human history. For over forty years space exploration, human have gotten more profound knowledge about outer space and life phenomena, ranging from understanding and recognizing space to adapting and utilizing space. With these development, space medicine that aimed at studying effect of space environment on human health and ensuring the safety, health and effective working of human in space exploration, will become increasingly improved and matured.The contents of research will develop from the early phenomena observation of the effect of space environment on human physiology and biochemistry, and the effect definition, to the study of the mechanism of changes of cell, molecule, and gene, from the passive adaptation for space environment to taking the initiative countermeasures, in order to ensure the safety, health and effective working of astronauts during space flight.Space practices in the past forty years have confirmed that a variety of physiological and pathological changes have been found for organism exposed to space flight. These changes include cardiovascular dysfunction, bone loss,muscle atrophy, decline of immune function, endocrine function disorder and space motion sickness. In recent years, more attention has been focused on the study of the mechanism of these changes, especially the effects of space environment on cell, molecule and its gene expression. With the demand of China's manned space engineering task and continuous development, a series of studies on medical problem caused by space environment have been carried out.     

Space flight experiment on Chinese silkworm on board the Russian 10th Biosatellite.

Space flight experiments on Chinese silkworm (Bombyx mori L.) were conducted on board the Russian 10th Biosatellite for 12 days. The samples included silkworm eggs, larvae, cocoons, pupae and moths. The processes of spinning, cocooning, mating, oviposition, larval hatching, pupation and moth emergence all completed well in space. The following effects of space flight on silkworm development were observed: The times of hatching and oviposition in the flight group were 2 to 3 days earlier than in the control group; the hatching rate of diapause eggs during space flight seemed higher than that of the control group; the life span of 2 of the 7 varieties flown was shortened; genetical variations appeared in 3 varieties. The results showed that the embryonic stage was probably the period most sensitive to the space flight environment.     

太空环境对肿瘤细胞生理特性的影响

将3种肿瘤细胞搭载于“神舟4号”的卫星返回舱内,经过7天太空飞行,回收后对存活细胞进行单克隆化,观察细胞形态,并测定了细胞周期、黏附力及细胞因子表达.结果显示,经太空飞行,小鼠黑色素瘤B16细胞的周期发生改变,G1期细胞明显增多(p<0.05),并表现多种细胞形态;人肺鳞癌细胞L78对血管内皮细胞黏附力明显减弱,但经传代培养其黏附力恢复且超过对照组细胞;Caski细胞IL-2、IL-8、TNF和TGF的表达均明显增加,而L78细胞上述4种细胞因子的表达均显著下降.结论,太空环境可影响肿瘤细胞的某些生理特性,但可否影响肿瘤细胞的免疫原性,仍需做进一步的实验.     

Biological dosimetry in Russian and Italian astronauts.

Large uncertainties are associated with estimates of equivalent dose and cancer risk for crews of long-term space missions. Biological dosimetry in astronauts is emerging as a useful technique to compare predictions based on quality factors and risk coefficients with actual measurements of biological damage in-flight. In the present study, chromosomal aberrations were analyzed in one Italian and eight Russian cosmonauts following missions of different duration on the MIR and the international space station (ISS). We used the technique of fluorescence in situ hybridization (FISH) to visualize translocations in chromosomes 1 and 2. In some cases, an increase in chromosome damage was observed after flight, but no correlation could be found between chromosome damage and flight history, in terms of number of flights at the time of sampling, duration in space and extra-vehicular activity. Blood samples from one of the cosmonauts were exposed in vitro to 6 MeV X-rays both before and after the flight. An enhancement in radiosensitivity induced by the spaceflight was observed.     

Effects of space flight and IGF-1 on immune function

We tested the hypothesis that insulin-like growth factor-1 (IGF-1) would ameliorate space flight-induced effects on the immune system. Twelve male, Sprague-Dawley rats, surgically implanted with mini osmotic pumps, were subjected to space flight for 10 days on STS-77. Six rats received 10 mg/kg/day of IGF-1 and 6 rats received saline. Flight animals had a lymphocytopenia and granulocytosis which were reversed by IGF-1. Flight animals had significantly higher corticosterone levels than ground controls but IGF-1 did not impact this stress hormone. Therefore, the reversed granulocytosis did not correlate with serum corticosterone. Space flight and IGF-1 also combined to induce a monocytopenia that was not evident in ground control animals treated with IGF-1 or in animals subjected to space flight but given physiological saline. There was a significant increase in spleen weights in vivarium animals treated with IGF-1, however, this change did not occur in flight animals. We observed reduced agonist-induced lymph node cell proliferation by cells from flight animals compared to ground controls. The reduced proliferation was not augmented by IGF-1 treatment. There was enhanced secretion of TNF, IL-6 and NO by flight-animal peritoneal macrophages compared to vivarium controls, however, O₂ secretion was not affected. These data suggest that IGF-1 can ameliorate some of the effects of space flight but that space flight can also impact the normal response to IGF-1.