Summary Report for the Technical Interchange Meeting: Circuits and Biomarkers of the Central Nervous System Relating to Astronaut Performance
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Joshua S Alwood↗
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Planned Investigations to Address Acute Central Nervous System Effects of Space Radiation Exposure with Human Performance Data
This work intends to generate evidence of acute, incremental human performance decrement similar to that due to space radiation and its impacts on the brain, to accompany ongoing human performance modeling work. The planned work will explore the boundaries of human behavioral and performance decrement after expo-sure to stress, which may be expected based in part on rodent responses found after exposure to ionizing radiation. The collection of evidence via simulation studies can characterize real human errors toward determining what stress levels lead to significantly-low levels of performance (below permissible outcome limits) which would imperil mission accomplishment. If mission-relevant yet animal-study-linked tasks are used, human and animal performance levels may be aligned to enable quantitative assignment of permissible exposure limits based on animal exposure studies. Ultimately, a transfer function between the performances of exposed rodents and humans under stress can be developed using shared impairment mechanisms.
human performance↗
The Need for Biological Countermeasures to Mitigate the Risk of Space Radiation-Induced Carcinogenesis, Cardiovascular Disease, and Central Nervous System Deficiencies
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Brock J. Sishc↗
Overview of the Neurolab Spacelab mission
Neurolab is a NASA Spacelab mission with multinational cooperative participation that is dedicated to research on the nervous system. The nervous systems of all animal species have evolved in a one-g environment and are functionally influenced by the presence of gravity. The absence of gravity presents a unique opportunity to gain new insights into basic neurologic functions as well as an enhanced understanding of physiological and behavioral responses mediated by the nervous system. The primary goal of Neurolab is to expand our understanding of how the nervous system develops, functions in, and adapts to microgravity space flight. Twenty-six peer reviewed investigations using human and nonhuman test subjects were assigned to one of eight science discipline teams. Individual and integrated experiments within these teams have been designed to collect a wide range of physiological and behavior data in flight as well as pre- and postflight. Information from these investigations will be applicable to enhancing the well being and performance of future long duration space travelers, will contribute to our understanding of normal and pathological functioning of the nervous system, and may be applied by the medical community to enhance the health of humans on Earth.
manned↗
The use of biomechanics in the study of movement in microgravity
As biomechanists interested in the adaptability of the human body to microgravity conditions, it appears that our job is not only to make sure that the astronauts can function adequately in space but also that they can function upon their return to Earth. This is especially significant since many of the projects now being designed at NASA concern themselves with humans performing for up to 3 years in microgravity. While the Extended Duration Orbiter flights may last 30 to 60 days, future flights to Mars using current propulsion technology may last from 2 to 3 years. It is for this range of time that the adaptation process must be studied. Specifically, biomechanists interested in space travel realize that human performance capabilities will change as a result of exposure to microgravity. The role of the biomechanist then is to first understand the nature of the changes realized by the body. These changes include adaptation by the musculoskeletal system, the nervous system, cardiorespiratory system, and the cardiovascular system. As biomechanists, it is also our role to take part in the development of countermeasure programs that involve some form of regular exercise. Exercise countermeasure programs should include a variety of modalities with full knowledge of the loads imposed on the body by these modalities. Any exercise programs that are to be conducted by the astronauts during space travel must consider the fact that the musculoskeletal and neuromuscular systems degrade as a function of flight duration. Additionally, it must be understood that the central nervous system modifies its output in the control of the human body during space flight and most importantly, we must prepare the astronauts for their return to one g.
Gregor, R. J.↗
Physiology of motion sickness symptoms
Motion sickness research is reviewed with the emphasis placed on theories developed to explain its symptomatology. A general review of central nervous system, autonomic nervous system, and neuroendocrine system involvement in the syndrome. Particular attention is given to signs, symptoms, and physiological correlates, methodological issues, and directions for future research based on a dynamic interactive systems model.
Harm, Deborah L.↗
Gravity Sensor Plasticity in the Space Environment
The ability of the brain to learn from experience and to adapt to new environments is recognized to be profound. This ability, called 'neural plasticity,' depends directly on properties of neurons (nerve cells) that permit them to change in dimension, sprout new parts called spines, change the shape and/or size of existing parts, and to generate, alter, or delete synapses. (Synapses are communication sites between neurons.) These neuronal properties are most evident during development, when evolution guides the laying down of a general plan of the nervous system. However, once a nervous system is established, experience interacts with cellular and genetic mechanisms and the internal milieu to produce unique neuronal substrates that define each individual. The capacity for experience-related neuronal growth in the brain, as measured by the potential for synaptogenesis, is speculated to be in the trillions of synapses, but the range of increment possible for any one part of the nervous system is unknown. The question has been whether more primitive endorgans such as gravity sensors of the inner ear have a capacity for adaptive change, since this is a form of learning from experience.
Ross, Muriel D.↗
Brain Aging Hallmarks: A Primer for Future Studies on Space Radiation Effects
As humankind endeavors to travel farther away from Earth, many questions remain to be solved to ensure proper preparation for deep space. Multiple spaceflight stressors can elicit adverse health outcomes including exposure to space radiation. Space radiation exposure has been identified by the National Aeronautics and Space Administration (NASA) as an important contributor to cancer, degenerative tissue diseases including cataracts, cardiovascular disease, immune system dysfunction and possible central nervous system decrements. The complexity of the human central nervous system makes it difficult to adequately recapitulate in experimental model systems, which hinders quantitative description of associated decrements. The brain aging hallmarks, as introduced by Mattson and Arumugam in 2018, are measurable cellular and molecular hallmarks that generally contribute to the aging process, describe an aging phenotype, and are part of the etiology of age-related neurodegenerative diseases. These hallmarks include mitochondrial dysfunction, accumulation of oxidatively damaged molecules (oxidative stress), impaired lysosome and proteasome function, dysregulation of neuronal calcium homeostasis, compromised adaptive cellular stress response, aberrant neuronal network activity, impaired deoxyribonucleic acid (DNA) repair, inflammation, impaired neurogenesis and dysregulated energy metabolism. Cellular senescence and telomere attrition may also be considered, though more evidence is needed to regard them as brain-specific hallmarks of aging. Radiation exposure has previously been correlated with aging etiology; therefore, investigating the effects of radiation exposure within the context of the hallmarks of brain aging may provide insights into potential health risks facing NASA astronauts, and may provide a means to identify disease processes that may be important targets for disease prevention or intervention. This work describes the hallmarks of brain aging and serves as a primer for future investigation into how the hallmarks of brain aging may compare and contrast with outcomes associated with exposure to the space radiation environment. Further, it will be useful in future identification of hallmarks that may be appropriate to target for radiation countermeasures specific to the central nervous system.
Vivian Lu↗
Neural control: Long-range prospects
The development of long term connections with the nervous system, are considered for direct transfer of information into the nervous system, and for direct readout of information from the nervous system. The study of basic neurophysiological control mechanisms operating in the nervous system is advocated for the investigation of potential applications of such developments. These applications depend strongly on the successful achievement of the first three objectives. An attempt is made to envision the social consequences of these developments.
Hambrecht, T.↗
Investigating Neuro-Consequences of Spaceflight Using Drosophila Melanogaster
Research on human acclimation to spaceflight, including the recent NASA's Twin Study, reports complex effects of the spaceflight environment on health, with both acute and prolonged changes in multiple tissues. Spaceflight includes multiple factors such as microgravity, ionizing radiation, physiological stress, and disrupted circadian rhythms, that have been shown to contribute to pathophysiological responses that target immunity, bone and muscle integrity, cardiovascular and nervous systems. In this study, we used a well-established spaceflight model organism, Drosophila melanogaster, to assess spaceflight-associated changes on the nervous system. With 75% disease gene orthology to humans, short generation time, large sample size and ease of genetic, neuronal and behavioral studies, Drosophila is an excellent model to study nervous system dysfunction. Here, we present results from MVP-Fly-01 spaceflight mission that was launched on SpaceX CRS-14. The MVP hardware (developed by Techshot) used in this mission enabled us to have an in-flight 1g centrifuge, to distinguish the changes resulting from gravity versus those induced by other environmental factors associated with spaceflight. We observe behavioral impairments (p<0.001) and synaptic deficits, including decreased synaptic connections (p<0.05), in 3rd instar larvae which were developed in space. Furthermore, space-grown microgravity adults show a decrease in neuronal (p<0.05) and dendritic field (p<0.01) in adult brains coupled with an increased number of apoptotic cells (p<0.001) compared to in-flight 1g controls, suggesting increased neuronal loss under spaceflight conditions. In summary, we observe that altered gravity leads to gross neurological deficits. To better understand the long-term effects of spaceflight on the nervous system, longitudinal and multigenerational changes were also identified. This study will help elucidate the different approaches to prevent nervous system dysfunction in astronauts during spaceflight, while also contributing to a better understanding of the pathways that are related to some CNS disorders on Earth.
Iyer, Janani↗
A study of the general dynamics of the physical-chemical systems in mammals Final report
Dynamic aspects of temperature regulating system, cardiovascular system, hormonal system, central nervous system, and behavior in mammals
Iberall, A. S.↗
A study of the general dynamics of the physical-chemical systems in mammals Final report
General dynamics of mammalian temperature regulating system, cardiovascular system, hormonal system, central nervous system, and behavior
Iberall, A. S.↗
Methods of investigation in space biology and medicine, transmission of biomedical data
Methods for in-flight monitoring of the cardiovascular system, respiratory system, vestibular system, central nervous system, and the musculoskeletal systems are described. Methods of data analysis are also discussed.
Bayevskiy, R. M.↗
Effect of Microgravity on Mammalian Lymphocytes
The effect of microgravity on mammalian system is an important and interesting topic for scientific investigation, since NASA s objective is to send manned flights to planets like Mars and eventual human colonization. The Astronauts will be exposed to microgravity environment for a long duration of time during these flights. Our objective of research is to conduct in vitro studies for the effect of microgravity on mammalian immune system and nervous system. We did our preliminary investigations by exposing mammalian lymphocytes and astrocyte cells to a microgravity simulator cell bioreactor designed by NASA and manufactured at Synthecon, Inc. (USA).Our initial results showed no significant change in cytokine expression in these cells up to a time period of 120 hours exposure. Our future experiments will involve exposure for a longer period of time.
Banerjee, H.↗
Abnormalities of the QT interval in primary disorders of autonomic failure
BACKGROUND: Experimental evidence shows that activation of the autonomic nervous system influences ventricular repolarization and, therefore, the QT interval on the ECG. To test the hypothesis that the QT interval is abnormal in autonomic dysfunction, we examined ECGs in patients with severe primary autonomic failure and in patients with congenital dopamine beta-hydroxylase (DbetaH) deficiency who are unable to synthesize norepinephrine and epinephrine. SUBJECTS AND METHODS: Maximal QT and rate-corrected QT (QTc) intervals and adjusted QTc dispersion [(maximal QTc - minimum QTc on 12 lead ECG)/square root of the number of leads measured] were determined in blinded fashion from ECGs of 67 patients with primary autonomic failure (36 patients with multiple system atrophy [MSA], and 31 patients with pure autonomic failure [PAF]) and 17 age- and sex-matched healthy controls. ECGs of 5 patients with congenital DbetaH deficiency and 6 age- and sex-matched controls were also analyzed. RESULTS: Patients with MSA and PAF had significantly prolonged maximum QTc intervals (492+/-58 ms(1/2) and 502+/-61 ms(1/2) [mean +/- SD]), respectively, compared with controls (450+/-18 ms(1/2), P < .05 and P < .01, respectively). A similar but not significant trend was observed for QT. QTc dispersion was also increased in MSA (40+/-20 ms(1/2), P < .05 vs controls) and PAF patients (32+/-19 ms(1/2), NS) compared with controls (21+/-5 ms(1/2)). In contrast, patients with congenital DbetaH deficiency did not have significantly different RR, QT, QTc intervals, or QTc dispersion when compared with controls. CONCLUSIONS: Patients with primary autonomic failure who have combined parasympathetic and sympathetic failure have abnormally prolonged QT interval and increased QT dispersion. However, QT interval in patients with congenital DbetaH deficiency was not significantly different from controls. It is possible, therefore, that QT abnormalities in patients with primary autonomic failure are not solely caused by lesions of the sympathetic nervous system, and that the parasympathetic nervous system is likely to have a modulatory role in ventricular repolarization.
Non-NASA Center↗
STS-90 Day 07 Highlights
On this seventh day of the STS-90 mission, the flight crew, Cmdr. Richard A. Searfoss, Pilot Scott D. Altman, and Mission Specialists Richard M. Linnehan, Dafydd Rhys Williams and Kathryn P. Hire, and Payload Specialists Jay C. Buckey and James A. Pawelczyk continue experiments that looks at the autonomic nervous system, the part of the nervous system that automatically controls blood pressure. These investigations are designed to uncover changes that take place in blood pressure control during space flight. Crewmembers use the Lower Body Negative Pressure (LBNP) device which places a stress on the cardiovascular system similar to what is experienced when standing in Earth's gravity environment.
Source record↗
Motor System Development Depends on Experience: A Microgravity Study of Rats
Animals move about their environment by sensing their surroundings and making adjustments according to need. All animals take the force of gravity into account when the brain and spinal cord undertake the planning and execution of movements. To what extent must animals learn to factor in the force of gravity when making neural calculations about movement? Are animals born knowing how to respond to gravity, or must the young nervous system learn to enter gravity into the equation? To study this issue, young rats were reared in two different gravitational environments (the one-G of Earth and the microgravity of low Earth orbit) that necessitated two different types of motor operations (movements) for optimal behavior. We inquired whether those portions of the young nervous system involved in movement, the motor system, can adapt to different gravitational levels and, if so, the cellular basis for this phenomenon. We studied two groups of rats that had been raised for 16 days in microgravity (eight or 14 days old at launch) and compared their walking and righting (ability to go from upside down to upright) and brain structure to those of control rats that developed on Earth. Flight rats were easily distinguished from the age-matched ground control rats in terms of both motor function and central nervous system structure. Mature surface righting predominated in control rats on the day of landing (R+O), while immature righting predominated in the flight rats on landing day and 30 days after landing. Some of these changes appear to be permanent. Several conclusions can be drawn from these studies: (1) Many aspects of motor behavior are preprogrammed into the young nervous system. In addition, several aspects of motor behavior are acquired as a function of the interaction of the developing organism and the rearing environment; (2) Widespread neuroanatomical differences between one-G- and microgravity-reared rats indicate that there is a structural basis for the adaptation to the rearing environment. These observations provide support for the idea that an animal's motor system adapts for optimal function within the environment experienced during a critical period in early postnatal life.
Walton, Kerry D.↗
Autonomic control of cardiac function and myocardial oxygen consumption during hypoxic hypoxia.
Investigation in 19 conscious dogs of the importance of the sympathetic nervous system in the coronary and cardiac response to altitude (hypoxic) hypoxia. Beta-adrenergic blockade was used to minimize the cardiac effect associated with sympathetic receptors. It is shown that the autonomic nervous system, and particularly the sympathetic nervous system, is responsible for the increase in ventricular function and myocardial oxygen consumption that occurs during hypoxia. Minimizing this response through appropriate conditioning and training may improve the operating efficiency of the heart and reduce the hazard of hypoxia and other environmental stresses, such as acceleration, which are encountered in advanced aircraft systems.
Erickson, H. H.↗