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Brain atlases and associated databases have great potential as gateways for navigating, accessing, and visualizing a wide range of neuroscientific data. Recent progress towards realizing this potential includes the establishment of probabilistic atlases, surface-based atlases and associated databases, combined with improvements in visualization capabilities and internet access.
Lower body negative pressure (LBNP) has been extensively used for decades in aerospace physiological research as a tool to investigate cardiovascular mechanisms that are associated with or underlie performance in aerospace and military environments. In comparison with clinical stand and tilt tests, LBNP represents a relatively safe methodology for inducing highly reproducible hemodynamic responses during exposure to footward fluid shifts similar to those experienced under orthostatic challenge. By maintaining an orthostatic challenge in a supine posture, removal of leg support (muscle pump) and head motion (vestibular stimuli) during LBNP provides the capability to isolate cardiovascular mechanisms that regulate blood pressure. LBNP can be used for physiological measurements, clinical diagnoses and investigational research comparisons of subject populations and alterations in physiological status. The applications of LBNP to the study of blood pressure regulation in spaceflight, groundbased simulations of low gravity, and hemorrhage have provided unique insights and understanding for development of countermeasures based on physiological mechanisms underlying the operational problems.
Smart medical systems are being developed to allow medical treatments to address alterations in chemical and physiologic status in real time. In a smart medical system, sensor arrays assess subject status, which is interpreted by computer processors that analyze multiple inputs and recommend treatment interventions. The response of the subject to the treatment is again assessed by the sensor arrays, thus closing the loop. An early form of "smart medicine" has been practiced in space to assess nutrition. Nutrient levels are assessed with food frequency questionnaires, which are interpreted by flight surgeons to recommend inflight alterations in diet. In the future, sensor arrays will directly probe body chemistry. Near-infrared spectroscopy can be used to non-invasively measure several blood and tissue parameters that are important in the assessment of nutrition and fitness. In particular, this technology can be used to measure blood hematocrit and interstitial fluid pH. The non-invasive measurement of interstitial pH is discussed as a surrogate for blood lactate measurement for the development and real-time assessment of exercise protocols in space. Earth-based application of these sensors is also described.
Conducting research during actual or simulated weightlessness is a challenging endeavor, where even the simplest activities may present significant challenges. This article reviews some of the potential obstacles associated with performing research during space flight and offers brief descriptions of current and previous space research platforms and ground-based analogs, including those for human, animal, and cell-based research. This review is intended to highlight the main issues of space flight research analogs and leave the specifics for each physiologic system for the other papers in this section.
Food systems and meal components are constantly under review and development at the National Aerospace and Space Administration. The goal of this work is to generate a diet that meets the nutrient requirements of astronauts and satiates them. The constraints involved in shorter- and longer-term missions are described. The insight provided by observations of astronauts from the Skylab and Shuttle eras will allow researchers to consider the fact that, for any nutritional regimen to work, it must consider the limitations and taste buds of the individuals involved. Otherwise, the best diet design generated by their work may never be consumed.
The development of space food has been evolving since the Soviet cosmonaut, German Titov, became the first human to eat in space in August 1961. John Glenn was the first American to consume food, applesauce, on the third manned Mercury mission in August 1962. Before these events, there was no knowledge that humans would be able to swallow and, hence, eat in weightlessness. Space food development began with highly engineered foods that met rigid requirements imposed by spacecraft design and short mission durations. Improvements in the habitability of the spacecraft have permitted improvements in the quality of space food. As the missions became longer, the need for better nutrition, more variety, and easily consumable foods also became more important. Currently, the International Space Station astronauts have a wide variety of foods. The goal is to provide acceptable foods that taste similar to foods we eat here on Earth. Extended planetary stays will require even more variety and more technologic advances. Plants will be grown to recycle the air and water and will provide food for the crew. These harvested crops will need to be processed into safe, healthy, and acceptable food ingredients that can then be prepared into menu items.
The closed environment and limited evasive capabilities inherent in space flight cause astronauts to be exposed to many potential harmful agents (chemical contaminants in the environment and cosmic radiation exposure). Current power systems used to achieve space flight are prohibitively expensive for supporting the weight requirements to fully shield astronauts from cosmic radiation. Therefore, radiation poses a major, currently unresolvable risk for astronauts, especially for long-duration space flights. The major detrimental radiation effects that are of primary concern for long-duration space flights are damage to the lens of the eye, damage to the immune system, damage to the central nervous system, and cancer. In addition to the direct damage to biological molecules in cells, radiation exposure induces oxidative damage. Many natural antioxidants, whether consumed before or after radiation exposure, are able to confer some level of radioprotection. In addition to achieving beneficial effects from long-known antioxidants such as vitamins E and C and folic acid, some protection is conferred by several recently discovered antioxidant molecules, such as flavonoids, epigallocatechin, and other polyphenols. Somewhat counterintuitive is the protection provided by diets containing elevated levels of omega-3 polyunsaturated fatty acids, considering they are thought to be prone to peroxidation. Even with the information we have at our disposal, it will be difficult to predict the types of dietary modifications that can best reduce the risk of radiation exposure to astronauts, those living on Earth, or those enduring diagnostic or therapeutic radiation exposure. Much more work must be done in humans, whether on Earth or, preferably, in space, before we are able to make concrete recommendations.
It is very likely that the human immune system will be altered in astronauts exposed to the conditions of long-term space flight: isolation, containment, microgravity, radiation, microbial contamination, sleep disruption, and insufficient nutrition. In human and animal subjects flown in space, there is evidence of immune compromise, reactivation of latent virus infection, and possible development of a premalignant or malignant condition. Moreover, in ground-based space flight model investigations, there is evidence of immune compromise and reactivation of latent virus infection. All of these observations in space flight itself or in ground-based models of space flight have a strong resonance in a wealth of human pathologic conditions involving the immune system where reactivated virus infections and cancer appear as natural consequences. The clinical conditions of Epstein-Barr-driven lymphomas in transplant patients and Kaposi's sarcoma in patients with autoimmune deficiency virus come easily to mind in trying to identify these conditions. With these thoughts in mind, it is highly appropriate, indeed imperative, that careful investigations of human immunity, infection, and cancer be made by space flight researchers.
Exercise and nutrition represent primary countermeasures used during space flight to maintain or restore maximal aerobic capacity, musculoskeletal structure, and orthostatic function. However, no single exercise, dietary regimen, or combination of prescriptions has proven entirely effective in maintaining or restoring cardiovascular and musculoskeletal functions to preflight levels after prolonged space flight. As human space flight exposures increase in duration, identification, assessment, and development of various effective exercise- and nutrition-based protective procedures will become paramount. The application of adequate dietary intake in combination with effective exercise prescription will be based on identification of basic physiologic stimuli that maintain normal function in terrestrial gravity, and understanding how specific combinations of exercise characteristics (e.g., duration, frequency, intensity, and mode) can be combined with minimal nutritional requirements that mimic the stimuli normally produced by living in Earth's gravity environment. This can be accomplished only with greater emphasis of research on ground-based experiments targeted at understanding the interactions between caloric intake and expenditure during space flight. Future strategies for application of nutrition and exercise countermeasures for long-duration space missions must be directed to minimizing crew time and the impact on life-support resources.
Space flight is associated with an increase in oxidative stress after return to 1g. The effect is more pronounced after long-duration space flight. The effects lasts for several weeks after landing. In humans there is increased lipid peroxidation in erythrocyte membranes, reduction in some blood antioxidants, and increased urinary excretion of 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine. Isoprostane 8-iso-prostaglandin F(2alpha) and 8-oxo-7,8 dihydro-2 deoxyguanosine are markers for oxidative damage to lipids and DNA, respectively. The changes have been attributed to a combination of the energy deficiency that occurs during flight and substrate competition for amino acids occurring between repleting muscle and other tissues during the recovery phase. The observations in humans have been complemented by rodent studies. Most rodent studies showed increased production of lipid peroxidation products postflight and decreased antioxidant enzyme activity postflight. The rodent observations were attributed to the stress associated with reentry into Earth's gravity. Decreasing the imbalance between the production of endogenous oxidant defenses and oxidant production by increasing the supply of dietary antioxidants may lessen the severity of the postflight increase in oxidative stress.
Space flight anemia is a widely recognized phenomenon in astronauts. Reduction in circulating red blood cells and plasma volume results in a 10% to 15% decrement in circulatory volume. This effect appears to be a normal physiologic adaptation to weightlessness and results from the removal of newly released blood cells from the circulation. Iron availability increases, and (in the few subjects studied) iron stores increase during long-duration space flight. The consequences of these changes are not fully understood.
There is a growing body of evidence from the National Aeronautics and Space Administration and the Russian space program showing that humans exposed to the microgravity environment of space have a greater risk for developing renal stones. Increased bone resorption and the attendant hypercalciuria and hyperphosphaturia contribute significantly to raising the urinary state of saturation with respect to the calcium salts, namely calcium oxalate and calcium phosphate. In addition, other environmental and dietary factors may adversely affect urine composition and increase stone formation risk during space flight. For example, reductions in urinary volume, pH, and citrate contribute to raising stone formation risk. In addition to raising the risk for calcium stone formation, this metabolic profile is conducive to the formation of uric acid stones. Although observations to date have suggested that there may actually be a reduced food intake during the early phase of flight, crew members on longer-duration flights may increase food intake and be at increased risk for stone formation. Taken together, these findings support the use of nutritional recommendations for crew members that would serve to reduce the stone-forming propensity of the urinary environment. Pharmacologic intervention should be directed at raising urinary volumes, diminishing bone losses, and preventing reductions in urinary pH and citrate. Success in reducing the risk for stone formation in astronauts would also be of potential major benefit to the estimated 20 million Americans with nephrolithiasis.
Weightlessness induces bone loss. Understanding the nature of this loss and developing means to counteract it are significant challenges to potential human exploration missions. This article reviews the existing information from studies of bone and calcium metabolism conducted during space flight. It also highlights areas where nutrition may play a specific role in this bone loss, and where countermeasures may be developed to mitigate that loss.
Nearly three decades of space flight research have suggested that there are subclinical diabetogenic changes that occur in microgravity. Alterations in insulin secretion, insulin sensitivity, glucose tolerance, and metabolism of protein and amino acids support the hypothesis that insulin plays an essential role in the maintenance of muscle mass in extended-duration space flight. Experiments in flight and after flight and ground-based bedrest studies have associated microgravity and its experimental paradigms with manifestations similar to those of diabetes, physical inactivity, and aging. We propose that these manifestations are characterized best by an etiology that falls into the clinical category of "other" causes of diabetes, including, but not restricted to, genetic beta-cell defects, insulin action defects, diseases of the endocrine pancreas, endocrinopathies, drug or chemically induced diabetes, infections, immune-mediated metabolic alteration, and a host of genetic related diseases. We present data showing alterations in tumor necrosis factor-alpha production, insulin secretion, and amino acid metabolism in pancreatic islets of Langerhans cultured in a ground-based cell culture bioreactor that mimics some of the effects of microgravity. Taken together, space flight research, ground-based studies, and bioreactor studies of pancreatic islets of Langerhans support the hypothesis that the pancreas is unable to overcome peripheral insulin resistance and amino acid dysregulation during space flight. We propose that measures of insulin secretion and insulin action will be necessary to design effective countermeasures against muscle loss, and we advance the "disposition index" as an essential model to be used in the clinical management of space flight-induced muscle loss.
Space flight and the accompanying diminished muscular activity lead to a loss of body nitrogen and muscle function. These losses may affect crew capabilities and health in long-duration missions. Space flight alters protein metabolism such that the body is unable to maintain protein synthetic rates. A concomitant hypocaloric intake and altered anabolic/catabolic hormonal profiles may contribute to or exacerbate this problem. The inactivity associated with bedrest also reduces muscle and whole-body protein synthesis. For this reason, bedrest provides a good model for the investigation of potential exercise and nutritional countermeasures to restore muscle protein synthesis. We have demonstrated that minimal resistance exercise preserves muscle protein synthesis throughout bedrest. In addition, ongoing work indicates that an essential amino acid and carbohydrate supplement may ameliorate the loss of lean body mass and muscle strength associated with 28 d of bedrest. The investigation of inactivity-induced alterations in protein metabolism, during space flight or prolonged bedrest, is applicable to clinical populations and, in a more general sense, to the problems associated with the decreased activity that occur with aging.
Fluid and energy metabolism and related endocrine changes have been studied nearly from the beginning of human space flight in association with short- and long-duration flights. Fluid and electrolyte nutrition status is affected by many factors including the microgravity environment, stress, changes in body composition, diet, exercise habits, sleep cycles, and ambient temperature and humidity conditions. Space flight exposes astronauts to all these factors and consequently poses significant challenges to establishing dietary water, sodium, potassium, and energy recommendations. The purpose of this article is to review the results of ground-based and space flight research studies that have led to current water, electrolyte, and energy dietary requirements for humans during space flight and to give an overview of related endocrinologic changes that have been observed in humans during short- and long-duration space flight.
Circadian clocks have evolved to predict and coordinate physiologic processes with the rhythmic environment on Earth. Space studies in non-human primates and humans have suggested that this clock persists in its rhythmicity in space but that its function is altered significantly in long-term space flight. Under normal circumstances, the clock is synchronized by the light-dark cycle via the retinohypothalamic tract and the suprachiasmatic nucleus. It is also entrained by restricted feeding regimes via a suprachiasmatic nucleus-independent circadian oscillator. The site of this suboscillator (or oscillators) is not known, but new evidence has suggested that peripheral tissues in the liver and viscera may express circadian clock function when forced to do so by restricted feeding schedules or other homeostatic disruptions. New research on the role of the circadian clock in the control of feeding on Earth and in space is warranted.
Anthropogenic aerosols are intricately linked to the climate system and to the hydrologic cycle. The net effect of aerosols is to cool the climate system by reflecting sunlight. Depending on their composition, aerosols can also absorb sunlight in the atmosphere, further cooling the surface but warming the atmosphere in the process. These effects of aerosols on the temperature profile, along with the role of aerosols as cloud condensation nuclei, impact the hydrologic cycle, through changes in cloud cover, cloud properties and precipitation. Unravelling these feedbacks is particularly difficult because aerosols take a multitude of shapes and forms, ranging from desert dust to urban pollution, and because aerosol concentrations vary strongly over time and space. To accurately study aerosol distribution and composition therefore requires continuous observations from satellites, networks of ground-based instruments and dedicated field experiments. Increases in aerosol concentration and changes in their composition, driven by industrialization and an expanding population, may adversely affect the Earth's climate and water supply.