Developmental testing of the Advanced Animal Habitat to determine compatibility with rats and mice

The Research Animal Holding Facility (RAHF) and the Animal Enclosure Module (AEM) have housed rats during Space Shuttle flights since the 1980s, but the operational constraints of the hardware have limited the scientific return from these Shuttle flights. The RAHF provides environmental control and monitoring for 24 rats with in-flight animal access, but it must be flown in the Spacelab. Due to the infrequent availability of Spacelab flights, rodent experiments rely heavily on the AEM. Unfortunately, the AEM supports only six rats, has no environmental control and provides no animal access in flight. The Advanced Animal Habitat (AAH) is being developed to support up to 12 adult rats or 30 adult mice for up to 30 days, provide active temperature control, animal telemetry and on-orbit video, record environmental parameters in the animal cage, and provide in-flight animal access in the Middeck, the Spacelab or the Space Station. To ensure the AAH can meet these requirements, animal testing is being conducted with rats and mice in every step of development. Testing began with the cage configuration.     

The problem of artificial gravity: The current state and prospects

The review deals with the use of artificial gravity in manned space flights. The need for studying this problem is substantiated, with special emphasis on its implications for future interplanetary flights. The deconditioning of astronauts and a loss of their tolerance to gravitational loads despite the use of various preventive procedures are briefly discussed. The efficiency of artificial gravity generated by a short-arm centrifuge (SAC) is evaluated; the possibility of the use of an SAC in space flights (the effect of the main parameters of G-load on humans, and its tolerability, efficiency, etc.) is considered. Both Russian and foreign data are presented on the use of SAC for simulating microgravity effects under ground-based conditions (immersion and ANOH) and in experiments on board biosatellites. It is emphasized that all the data (both original and the data in the literature) testify to the efficiency of SAC as a preventive and therapeutic facility alleviating the negative effects of simulated microgravity. The problems that have not been resolved to date are also presented.     

Comparative efficiency of different regimens of locomotor training in prolonged space flights as estimated from the data on biomechanical and electromyographic parameters of walking

Biomechanical and electromyographic characteristics of locomotion were studied before and after a space flight on days 3, 7, and 10 after landing in 18 participants of prolonged space missions on board the International Space Station. It has been shown that microgravity causes significant changes in biomechanical and electromyographic characteristics of walking, such as a decrease in the amplitude of angular displacement in leg joints, a decrease in the double step length, and an increase in the electromyographic costs of locomotion. It has been also shown that interval locomotor physical training, such as alternation of running and walking, in prolonged space flights prevents an increase in the physiological costs of locomototions after a space flight and provides more efficient maintenance of the neuromuscular system’s performance after a flight. Cosmonauts who performed interval locomotor training had fewer changes in biomechanical and electromyographic characteristics of walking.     

Changes in gene expression and signal transduction in microgravity

Studies from space flights over the past three decades have demonstrated that basic physiological changes occur in humans during space flight. These changes include cephalic fluid shifts, loss of fluid and electrolytes, loss of muscle mass, space motion sickness, anemia, reduced immune response, and loss of calcium and mineralized bone. The cause of most of these manifestations is not known and until recently, the general approach was to investigate general systemic changes, not basic cellular responses to microgravity. This laboratory has recently studied gene growth and activation of normal osteoblasts (MC3T3-El) during spaceflight. Osteoblast cells were grown on glass coverslips and loaded in the Biorack plunger boxes. The osteoblasts were launched in a serum deprived state, activated in microgravity and collected in microgravity. The osteoblasts were examined for changes in gene expression and signal transduction. Approximately one day after growth activation significant changes were observed in gene expression in 0-G flight samples. Immediate early growth genes/growth factors cox-2, c-myc, bcl2, TGF beta1, bFGF and PCNA showed a significant diminished mRNA induction in microgravity FCS activated cells when compared to ground and 1-G flight controls. Cox-1 was not detected in any of the samples. There were no significant differences in the expression of reference gene mRNA between the ground, 0-G and 1-G samples. The data suggest that quiescent osteoblasts are slower to enter the cell cycle in microgravity and that the lack of gravity itself may be a significant factor in bone loss in spaceflight. Preliminary data from our STS 76 flight experiment support our hypothesis that a basic biological response occurs at the tissue, cellular, and molecular level in 0-G. Here we examine ground-based and space flown data to help us understand the mechanism of bone loss in microgravity.     

Immune suppression of human lymphoid tissues and cells in rotating suspension culture and onboard the International Space Station

The immune responses of human lymphoid tissue explants or cells isolated from this tissue were studied quantitatively under normal gravity and microgravity. Microgravity was either modeled by solid body suspension in a rotating, oxygenated culture vessel or was actually achieved on the International Space Station (ISS). Our experiments demonstrate that tissues or cells challenged by recall antigen or by polyclonal activator in modeled microgravity lose all their ability to produce antibodies and cytokines and to increase their metabolic activity. In contrast, if the cells were challenged before being exposed to modeled microgravity suspension culture, they maintained their responses. Similarly, in microgravity in the ISS, lymphoid cells did not respond to antigenic or polyclonal challenge, whereas cells challenged prior to the space flight maintained their antibody and cytokine responses in space. Thus, immune activation of cells of lymphoid tissue is severely blunted both in modeled and true microgravity. This suggests that suspension culture via solid body rotation is sufficient to induce the changes in cellular physiology seen in true microgravity. This phenomenon may reflect immune dysfunction observed in astronauts during space flights. If so, the ex vivo system described above can be used to understand cellular and molecular mechanisms of this dysfunction.     

微重力环境影响植物生长发育的研究进展

微重力是最独特的空间环境条件之一,研究微重力对不同植物种类以及不同植物部位的影响是空间生物学的重要内容之一,对于建立生物再生式生命保障系统意义重大。生物再生式生命保障系统是未来开展长期载人空间活动的核心技术,其优势在于能在一个密闭的系统内持续再生氧气,水和食物等高等动物生活必需品,植物部件是生物再生式生命保障系统的重要组成部分。了解和掌握微重力对植物生长发育的影响,有助于采取有效的作业制度确保其正常生长发育和繁殖,是成功建立生物再生式生命保障系统的首要关键。该文就植物在空间探索中的地位和作用,地面模拟微重力的装置以及国内外有关微重力对植物的影响做一综述。现有的研究结果包括,未来长期的载人航天任务需要植物通过光合作用为生物再生式生命保障系统提供部分动物营养、洁净水以及清除系统中的固体废物和二氧化碳;三维随机回旋装置是目前地面上模拟微重力效应的主要装置之一,尤其适用于植物材料的长期模拟微重力处理;国内外有关微重力对植物影响的报道生理生化水平多集中在植物的生长发育和生理反应,比如表型变化或者与重力相关的激素或者钙离子的再分配,细胞或亚细胞水平主要有细胞壁、线粒体、叶绿体以及细胞骨架等,基因和蛋白质表达水平的研究对象主要为拟南芥。由于实验方法和材料之间的差异,微重力对不同植物或者植物不同部位在各个水平的影响效果并不一致,未来需要开展更多的相关研究工作。     

Current problems of space cardiology

The development of space cardiology is considered, from the first flights of animals and humans to the studies conducted on board International Space Station (ISS). The material is recounted in four sections in accordance with the theoretical statements presented in the book “Space Cardiology” (1967). The first section is analysis of rearrangement of blood circulation under the conditions of microgravity. Long-term microgravity has been demonstrated to require mobilization of additional functional reserves of the body. During the first six months of the flight, the cardiovascular homeostasis is supported by the regulatory mechanisms of the blood circulation system, whereas in the case of a more prolonged impact of microgravity, intersystem control is actively involved (suprasegmental divisions of autonomic regulation). In the second section dealing with the roles of the right and left divisions of the heart in adaptation to microgravity of the cardiovascular system, the important role of the right heart at the initial stage of a space flight (SF) is emphasized. The third section addresses the problem of reducing the orthostatic stability; this study has been initiated as early as the first manned space flights. The results obtained on board ISS testify to the importance of evaluating the functional reserves of the blood circulation system. The fourth section presents data on the new methods of myocardial examination that are to be soon introduced into SF medical provision. In conclusion, some new projects in space cardiology are discussed.     

Ophthalmic changes associated with long-term exposure to microgravity

The review discusses recent foreign publications on the problem of ophthalmic changes associated with long-term effects of microgravity during space flights. The states including hyperopic shift of refraction, a change in intraocular pressure, increased intracranial pressure, alterations in the choroid and retinal tissues, and optic disk swelling have been described. These effects are caused by redistribution of blood and fluid to the upper part of the body, increased intracranial pressure, and congestion of venous blood and lymph in the upper part of the body and head. Other factors that may trigger microgravity-induced vision impairment have also been considered. Photographic illustrations of changes have been provided.     

Analysis of possible causes of activation of gastric and the pancreatic excretory and incretory function after completion of space flight at the international space station

A comparative analysis of the excretory and incretory activity of the stomach and pancreas in astronauts soon after completion of space flights of various durations was performed. An increase in the fasting activity of gastric and pancreatic enzymes and hormones (insulin and C-peptide) in blood, reflecting the increased excretory and incretory activity of organs of the gastroduodenal region developing in microgravity, was demonstrated. The absence of subjects infected with Helicobacter pylori in the space flight crew excluded the involvement of this microorganism in the mechanism underlying the increase in the gastric secretory activity. The absence of correlation between the increase in the secretory activity of organs of the gastroduodenal region and the duration of the space flight allowed us to rule out the hypokinetic mechanism, which is associated with the duration of exposure to microgravity. It was concluded that the main mechanism underlying the changes in the functional state of the digestive system in space flight may be determined by the rearrangement of the venous hemodynamics of organs of the abdominal cavity, unrelated to the duration of exposure to microgravity. It was shown that, after completion of space flights and in ground-based experiments simulating the hemodynamic rearrangement occurring in microgravity, the increase in the basal excretory activity of gastroduodenal organs was not caused by gastrin secretion and occurred simultaneously with an increase in the secretion of insulin, which is considered as a putative hormonal component of the hemodynamic mechanism.     

Psychophysiological issues of manned space flights

The article deals with some issues of psychophysiological support (PPS) of manned space flights discussed with Academician O.G. Gazenko. It has been shown that even at the initial stages of development of space flights (SFs), monitoring and evaluation of the mental state and working capacity of crew members were regarded as the key components of PPS and merited special comprehensive studies with the development of associated methods. The polyeffectors method for recording physiological functions, such as electrocardiogram, electroencephalogram, and skin-galvanic reaction, was recognized as a potent tool in gathering information for the assessment of the current state of health. In the period of the performance of long-term orbital flights, starting with the 96-day flight of Yu. Romanenko and G. Grechko, the system of psychological support developed at the Institute for Biomedical Problems (IBMP), under the leadership of Gazenko was introduced into PPS, and then used in all flights of the stations Salyut and Mir, and now at the International Space Station. Evidently, the use of this system made a significant contribution to the PPS and maintenance of health and working efficiency of crews.     

The system of preventive measures in long space flights

The article summarizes the results of the development of preventive measures (PMs) performed by the team headed by Academician O.G. Gazenko (winner of the State Prize), as well as some data obtained in the following years at the Institute of Biomedical Problems of the Russian Academy of Sciences, where these measures were further developed. The system of prevention of adverse changes in the body of cosmonauts, which was first developed in Russia, provided successful implementation of long-term space flights (SFs) on board series of orbital stations (OSs) Salyut and the station Mir, which lasted from 64 to 438 days. This system includes performing physical exercises on a treadmill and bicycle ergometer, axial loading along the longitudinal axis of the human body by means of a Penguin suit, application of negative pressure to the lower part of the body by means of a pneumatic-vacuum spacesuit Chibis, and some other means. This system proved to be highly efficient, preventing or considerably decreasing the negative effects of microgravity throughout and after prolonged space flights.     

Activation of microcarrier-attached lymphocytes in microgravity

A technology has been developed to achieve optimal attachment of adhesion-independent lymphocytes to microcarrier beads. The activation of T-lymphocytes by concanavalin A was tested under microgravity conditions in an experiment carried out in space during the first Spacelab Life Science Mission. Activation, measured as the synthesis of deoxyribonucleic acid (DNA) and the production of interferon-gamma, more than doubled in attached lymphocytes in microgravity. The depression of the activation discovered in previous space experiments is due to an impairment not of the lymphocyte but of the macrophage function. The system described here may be useful for radiobiological investigations on the effect of high-energy particles and for testing the efficiency of the immune system in humans during the long-duration space flight planned in the future. The biotechnological significance of the increased lymphokine production in space remains to be assessed.     

Effect of microgravity on renal and femoral flows during LBNP & intravenous saline load

Renal and femoral hemodynamics were studied in crew members at rest and during lower body negative pressure before and after the D-2 Spacelab mission and with intravenous saline loading. Specific measurements included renal vascular resistance, femoral arterial flow, and vascular resistance, along with other cardiovascular parameters. Cardiovascular adaptation to microgravity is discussed with a focus on changes observed in femoral and renal vascular resistance.     

Cytogenetic characteristic of osteogenic cells in vitro as perspective predictors of osteopenia under microgravity

Mechanical stimulation of bone tissue determined by earth gravity is one of the main factors mediating the nature, rate and direction of functional adaptation of the bone system in the process of onto- and phylogenesis. Theoretically expected losses of bone mass under condition of mechanical load deficit under microgravity (osteopenia, osteoporosis) may become a factor that limits the duration of space flights. As a result of long-term studies some properties and regularities of change in human tissue after prolonged space flights (for 5-7 months) were established.     

A policy of anticipation as a strategic objective of space biology and medicine at the present stage

This article reflects the ongoing debates in Russia regarding paths of innovative development and the role that fundamental science has played in the development of technology critical for national security and for its breakthrough potential. Alternative routes of technical development include variations in priority support for those points of growth, in which Russia has attained and steadily held the leading position, occupying a prominent place in the international division of labor. Russia’s space program is a good example of the successful implementation of a national program and provides a demonstration of the country’s leadership role in this area of human activities. This article presents an analysis of the factors and circumstances in Russia that predetermined, in the early, “Gagarin” period of piloted space flights, its winning of the leading position. They also determined the vector of the development of manned space flight for many years to come. Even taking into account the host of issues with the implementation of the International Space Station (ISS) utilization program and the planning of manned flights to the Moon and Mars, the unique experience of preparations and the conducting of research and tests with humans in space—the enormous groundwork in fundamental biomedical research over the past 50 years of piloted flights—provides the basis for an optimistic prognosis for gaining headway with essentially new, ambitious space projects. The key question is whether the proactive strategy of prioritized development and the affirmation of the role of manned space flights as the most integrated and science-intensive sector of innovative achievement will be realized. The development of the space industry depends upon the answer, not only at the present stage but in the long-term as well, as does the fate of the national fundamental space sciences, an integral part of which is space biomedicine.     

The effects of weightlessness on the human organism and mammalian cells

It has always been a desire of mankind to conquest Space. A major step in realizing this dream was the completion of the International Space Station (ISS). Living there for several months confirmed early observations of short-term spaceflights that a loss of gravity affects the health of astronauts. Space medicine tries to understand the mechanism of microgravity-induced health problems and to conceive potent countermeasures. There are four different aspects which make space medicine appealing: i) finding better strategies for adapting astronauts to weightlessness; ii) identification of microgravity-induced diseases (e.g. osteoporosis, muscle atrophy, cardiac problems and others); iii) defining new therapies to conquer these diseases which will benefit astronauts as well as people on Earth in the end; and iv) on top of that, unveiling the mechanisms of weightlessness-dependent molecular and cellular changes is a requirement for improving space medicine. In mammalian cells, microgravity induces apoptosis and alters the cytoskeleton and affects signal transduction pathways, cell differentiation, growth, proliferation, migration and adhesion. This review focused on gravi-sensitive signal transduction elements and pathways as well as molecular mechanisms in human cells, aiming to understand the cellular changes in altered gravity. Moreover, the latest information on how these changes lead to clinically relevant health problems and current strategies of countermeasures are reviewed.     

Vestibular Function after Repeated Space Flights

This paper presents the results from testing the vestibular function on return from repeated space flights (SF) in 32 cosmonauts of the International Space Station that were in long SFs of 125–215 days. The cosmonauts were tested twice before the flight (baseline data collection) and on days 1–2, 4–5, and 8–9 after landing. The testing was made using two methods for recording eye movements (with simultaneous recording of head movements): electro-oculography and video-oculography. It is shown that the repeated stay in the long SF leads to a considerable statistically significant reduction in the de-adaptation period. Atypical vestibular disorders and changed patterns of the otolith-semicircular canal interaction are observed mostly in the cosmonauts who have made their maiden flights to microgravity.     

Modeled gravitational unloading induced downregulation of endothelin-1 in human endothelial cells

Many space missions have shown that prolonged space flights may increase the risk of cardiovascular problems. Using a three-dimensional clinostat, we investigated human endothelial EA.hy926 cells up to 10 days under conditions of simulated microgravity (microg) to distinguish transient from long-term effects of microg and 1g. Maximum expression of all selected genes occurred after 10 min of clinorotation. Gene expression (osteopontin, Fas, TGF-beta(1)) declined to slightly upregulated levels or rose again (caspase-3) after the fourth day of clinorotation. Caspase-3, Bax, and Bcl-2 protein content was enhanced for 10 days of microgravity. In addition, long-term accumulation of collagen type I and III and alterations of the cytoskeletal alpha- and beta-tubulins and F-actin were detectable. A significantly reduced release of soluble factors in simulated microgravity was measured for brain-derived neurotrophic factor, tissue factor, vascular endothelial growth factor (VEGF), and interestingly for endothelin-1, which is important in keeping cardiovascular balances. The gene expression of endothelin-1 was suppressed under microg conditions at days 7 and 10. Alterations of the vascular endothelium together with a decreased release of endothelin-1 may entail post-flight health hazards for astronauts.     

Decreased Succinate Dehydrogenase Activity of Gamma and Alpha Motoneurons in Mouse Spinal Cords Following 13 Weeks of Exposure to Microgravity

Cell body size and succinate dehydrogenase activity of motoneurons in the dorsolateral region of the ventral horn in the lumbar and cervical segments of the mouse spinal cord were assessed after long-term exposure to microgravity and compared with those of ground-based controls. Mice were housed in a mouse drawer system on the International Space Station for 13 weeks. The mice were transported to the International Space Station by the Space Shuttle Discovery and returned to Earth by the Space Shuttle Atlantis. No changes in the cell body size of motoneurons were observed in either segment after exposure to microgravity, but succinate dehydrogenase activity of small-sized (<300 μm²) gamma and medium-sized (300–700 μm²) alpha motoneurons, which have higher succinate dehydrogenase activity than large-sized (>700 μm²) alpha motoneurons, in both segments was lower than that of ground-based controls. We concluded that exposure to microgravity for longer than 3 months induced decreased succinate dehydrogenase activity of both gamma and slow-type alpha motoneurons. In particular, the decreased succinate dehydrogenase activity of gamma motoneurons was observed only after long-term exposure to microgravity.