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NASA NTRS2024

Long-term effects of acute irradiation and isolation on crew age-matched mice

The future of space missions beyond low-Earth orbit presents exciting opportunities but may come with formidable health challenges. Astronauts face a unique combination of space stressors capable of exerting effects on the central nervous system (CNS) with possible sex-dependent differences. The interaction of these combined spaceflight stressors may induce oxidative stress, thereby altering brain integrity and behavioral performance. Understanding these changes is critical for safeguarding astronaut health and enabling successful exploration. By understanding the physiological responses to the combined effects of ionizing radiation (IR) and social isolation in the brain through immunohistochemistry (IHC), proteomics and cytokine expression analyses, we aim to identify CNS pathways ripe for countermeasure development to mitigate adverse brain changes with future deep space exploration. Here, we study the combined effects of simulated 5-ion galactic cosmic radiation (GCRsim) at acute dosage (5, 15, and 50 cGy) and social isolation on crew age-matched male and female mice at 124 days post-irradiation. We conducted analyses of hippocampal cytokine biomarkers and proteomic profiling on hippocampal lysates. Our findings reveal sex-specific regulation of hippocampal cytokines and proteomic profiles. Ongoing immunohistochemistry findings on the hippocampus will provide qualitative information regarding key protein expression and cellular changes such as microglial activation, blood brain barrier integrity, and neuroinflammation. With future plans for long-duration space missions, such as Mars exploration, understanding CNS changes over extended periods in mice can provide insights into potential long-term health impacts on astronauts. This project will provide us with valuable insights into sex-differences in neurobiological processes and disease mechanisms impacting men and women in space.

space radiation↗

NASA NTRS2015

Addressing Human System Risks to Future Space Exploration

NASA is contemplating future human exploration missions to destinations beyond low Earth orbit, including the Moon, deep-space asteroids, and Mars. While we have learned much about protecting crew health and performance during orbital space flight over the past half-century, the challenges of these future missions far exceed those within our current experience base. To ensure success in these missions, we have developed a Human System Risk Board (HSRB) to identify, quantify, and develop mitigation plans for the extraordinary risks associated with each potential mission scenario. The HSRB comprises research, technology, and operations experts in medicine, physiology, psychology, human factors, radiation, toxicology, microbiology, pharmacology, and food sciences. Methods: Owing to the wide range of potential mission characteristics, we first identified the hazards to human health and performance common to all exploration missions: altered gravity, isolation/confinement, increased radiation, distance from Earth, and hostile/closed environment. Each hazard leads to a set of risks to crew health and/or performance. For example the radiation hazard leads to risks of acute radiation syndrome, central nervous system dysfunction, soft tissue degeneration, and carcinogenesis. Some of these risks (e.g., acute radiation syndrome) could affect crew health or performance during the mission, while others (e.g., carcinogenesis) would more likely affect the crewmember well after the mission ends. We next defined a set of design reference missions (DRM) that would span the range of exploration missions currently under consideration. In addition to standard (6-month) and long-duration (1-year) missions in low Earth orbit (LEO), these DRM include deep space sortie missions of 1 month duration, lunar orbital and landing missions of 1 year duration, deep space journey and asteroid landing missions of 1 year duration, and Mars orbital and landing missions of 3 years duration. We then assessed the likelihood and consequences of each risk against each DRM, using three levels of likelihood (Low: less than or equal to 0.1%; Medium: 0.1%–1.0%; High: greater than or equal to 1.0%) and four levels of consequence ranging from Very Low (temporary or insignificant) to High (death, loss of mission, or significant reduction to length or quality of life). Quantitative evidence from clinical, operational, and research sources were used whenever available. Qualitative evidence was used when quantitative evidence was unavailable. Expert opinion was used whenever insufficient evidence was available. Results: A set of 30 risks emerged that will require further mitigation efforts before being accepted by the Agency. The likelihood by consequence risk assessment process provided a means of prioritizing among the risks identified. For each of the high priority risks, a plan was developed to perform research, technology, or standards development thought necessary to provide suitable reduction of likelihood or consequence to allow agency acceptance. Conclusion: The HSRB process has successfully identified a complete set of risks to human space travelers on planned exploration missions based on the best evidence available today. Risk mitigation plans have been established for the highest priority risks. Each risk will be reassessed annually to track the progress of our risk mitigation efforts.

Paloski, W. H.↗

NASA NTRS2017

Autogenic-Feedback Training Exercise (AFTE) Mitigates the Effects of Spatial Disorientation to Simulated Orion Spacecraft Re-Entry: Individual Differences

NASA has identified a potential risk of spatial disorientation to future astronauts during re-entry of the proposed Orion spacecraft. The purpose of this study was to determine if a 6-hour physiological training procedure, Autogenic-Feedback Training Exercise (AFTE), can mitigate these effects. Twenty subjects were assigned to two groups (AFTE and Control) matched for motion sickness susceptibility and gender. All subjects received a standard rotating chair test to determine motion sickness susceptibility; three training sessions on a manual performance task; and four exposures to a simulated Orion re-entry test in the rotating chair. Treatment subjects were given two hours of AFTE training before each Orion test. A diagnostic scale was used to evaluate motion sickness symptom severity. Results showed that 2 hours of AFTE significantly reduced motion sickness symptoms during the second Orion test. AFTE subjects were able to maintain lower heart rates and skin conductance levels and other responses than the control group subjects during subsequent tests. Trends show that performance was less degraded for AFTE subjects. The results of this study indicate that astronauts could benefit from receiving at least 2 hours of preflight AFTE. In addition, flight crews could benefit further by practicing physiologic self-regulation using mobile devices.

human performance↗

NASA NTRS2016

Microgravity-Induced Physiological Fluid Redistribution: Computational Analysis to Assess Influence of Physiological Parameters

Space flight impacts human physiology in many ways, the most immediate being the marked cephalad (headward) shift of fluid upon introduction into the microgravity environment. This physiological response to microgravity points to the redistribution of blood and interstitial fluid as a major factor in the loss of venous tone and reduction in heart muscle efficiency which impact astronaut performance. In addition, researchers have hypothesized that a reduction in astronaut visual acuity, part of the Visual Impairment and Intracranial Pressure (VIIP) syndrome, is associated with this redistribution of fluid. VIIP arises within several months of beginning space flight and includes a variety of ophthalmic changes including posterior globe flattening, distension of the optic nerve sheath, and kinking of the optic nerve. We utilize a suite of lumped parameter models to simulate microgravity-induced fluid redistribution in the cardiovascular, central nervous and ocular systems to provide initial and boundary data to a 3D finite element simulation of ocular biomechanics in VIIP. Specifically, the lumped parameter cardiovascular model acts as the primary means of establishing how microgravity, and the associated lack of hydrostatic gradient, impacts fluid redistribution. The cardiovascular model consists of 16 compartments, including three cerebrospinal fluid (CSF) compartments, three cranial blood compartments, and 10 thoracic and lower limb blood compartments. To assess the models capability to address variations in physiological parameters, we completed a formal uncertainty and sensitivity analysis that evaluated the relative importance of 42 input parameters required in the model on relative compartment flows and compartment pressures. Utilizing the model in a pulsatile flow configuration, the sensitivity analysis identified the ten parameters that most influenced each compartment pressure. Generally, each compartment responded appropriately to parameter variations associated with itself and adjacent compartments. However, several unexpected interactions between components, such as between the choroid plexus and the lower capillaries, were found, and are due to simplifications in the formulation of the model. The analysis illustrates that highly influential parameters and those that have unique influences within the model formulation must be tightly controlled for successful model application.

gravitational physiology↗

NASA NTRS1975

Physiological mechanisms of the effect of weightlessness on the body

Experimental data show that physiological reactions observed under weightlessness conditions are caused by: (1) The direct effect of weightlessness, as a consequence of decrease (""disappearance'') of the weight of body tissues and organs; and (2) the mediated effect of weightlessness, as a result of changes in the functional state of the central nervous system and the cooperative work of the analyzers. The human body adopts to weightless conditions under the prolonged effects of it. In this case, four periods can be distinguished: The first period, a transitional process lasting from 1 to 24 hours; second period, initial adaptation to conditions of weightlessness and readjustment of all functional systems of the body; the third period, adaptation to the unusual mechanical conditions of the external environment, lasting from 3 to 8 days and more; and the fourth period, the stage of possible imbalance of the functions and the systems of some astronauts, as a result of the prolonged effect of weightlessness.

Kasyan, I. I.↗

NASA NTRS2015

Evaluation of the Accuracy of Astroskin as a Behavioral Health Self-Monitoring System for Spaceflight

In space, there is a need to monitor astronauts' vital signs and assess their readiness to perform specific tasks during a mission. Currently, NASA does not have the capability to noninvasively monitor crew for extended periods of time. The Canadian Space Agency is working with the Psychophysiology Lab at NASA ARC to determine if the Astroskin could be used as a solution to this problem. Astroskin, a commercially available garment with built-in biosensors, can be comfortably worn under clothing or a spacesuit and relay information to the crewman's own mobile device. Data can also be sent wirelessly to the on-board Exploration Medical System. To determine if Astroskin meets requirements for health monitoring, it must first be validated in spaceflight analog environments. In the current study Astroskin data will be compared to traditional biomedical instrument measures of electrocardiography (ECG), respiration rate, and systolic blood pressure. The data will be recorded during Autogenic Feedback Training Exercise (AFTE), which is a type of physiological self-regulation training designed for astronauts. The data will also be recorded during simulations of the Orion spacecraft re-entry. The results to date suggest that Astroskin is a suitable ambulatory monitoring system that allows astronauts to self-diagnose and self-regulate adverse autonomic nervous system responses to sustained exposure to microgravity of spaceflight.

biomedical↗

NASA NTRS2016

Next Steps Toward Understanding Human Habitation of Space: Environmental Impacts and Mechanisms

Entry into low earth orbit and beyond causes profound shifts in environmental conditions that have the potential to influence human productivity, long term health, and even survival. We now have evidence that microgravity, radiation and/or confinement in space can lead to demonstrably detrimental changes in the cardiovascular (e.g. vessel function, orthostatic intolerance), musculoskeletal (muscle atrophy, bone loss) and nervous (eye, neurovestibular) systems of astronauts. Because of both the limited number of astronauts who have flown (especially females) and the high degree of individual variability in the human population, important unanswered questions about responses to the space environment remain: What are the sex differences with respect to specific physiological systems? Are the responses age-dependent and/or reversible after return to Earth? Do observed detrimental changes that resemble accelerated aging progress continuously over time or plateau? What are the mechanisms of the biological responses? Answering these important questions certainly demands a multi-pronged approach, and the study of multicellular model organisms (such as rodents and flies) already has provided opportunities for exploring those questions in some detail. Recent long duration spaceflight experiments with rodents show that mice in space provide a mammalian model that uniquely combines the influence of reduced gravitational loading with increased physical activity. In addition, multiple investigators have shown that ground-based models that simulate aspects of spaceflight (including rodent hind limb unloading to mimic weightlessness and exposure to ionizing radiation), cause various transient and persistent detrimental consequences in multiple physiological systems. In general, we have found that adverse skeletal effects of simulated weightlessness and space radiation when combined, can be quantitatively, if not qualitatively, different from the influence of each environmental factor alone implying at least some shared underlying mechanisms. Thus, both ground based and spaceflight research utilizing model organisms provide the opportunity to better understand environmental factors and biological mechanisms that contribute to human health and survival in space.

skeleton↗

NASA NTRS1999

Instrumentation for Non-Invasive Assessment of Cardiovascular Regulation

It is critically important to be able to assess alterations in cardiovascular regulation during and after space flight. We propose to develop an instrument for the non-invasive assessment of such alterations that can be used on the ground and potentially during space flight. This instrumentation would be used by the Cardiovascular Alterations Team at multiple sites for the study of the effects of space flight on the cardiovascular system and the evaluation of countermeasures. In particular, the Cardiovascular Alterations Team will use this instrumentation in conjunction with ground-based human bed-rest studies and during application of acute stresses e.g., tilt, lower body negative pressure, and exercise. In future studies, the Cardiovascular Alterations Team anticipates using this instrumentation to study astronauts before and after space flight and ultimately, during space flight. The instrumentation may also be used by the Bone Demineralization/Calcium Metabolism Team, the Neurovestibular Team and the Human Performance Factors, Sleep and Chronobiology Team to measure changes in autonomic nervous function. The instrumentation will be based on a powerful new technology - cardiovascular system identification (CSI) - which has been developed in our laboratory. CSI provides a non-invasive approach for the study of alterations in cardiovascular regulation. This approach involves the analysis of second-to-second fluctuations in physiologic signals such as heart rate and non-invasively measured arterial blood pressure in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of multiple physiologic mechanisms, CSI provides a closed-loop model of the cardiovascular regulatory state in an individual subject.

Cohen, Richard J.↗

NASA NTRS1973

Effects of weightlessness in man.

The program for the Apollo 16 flight was designed to include both safeguards against and investigations of the physiological problems arising from increase in the period of manned space flight. Precautions included the provision of a controlled diet with high potassium content, carefully controlled work loads and work-rest cycles, and an emergency cardiology consultation service, and investigations were made to enable preflight vs postflight comparisons of metabolic, cardiovascular, and central nervous system data. Results of these investigations indicate that adjustment to weightlessness can be satisfactorily assisted by appropriate countermeasures, including attention to diet.

Berry, C. A.↗

NASA NTRS1985

Stimulus specificity and individual stereotypy of autonomic responses to motion stressors

Motion sickness research shows a lack of agreement regarding the contribution of the autonomic nervous system (ANS). The resolution of this question is exigent for Space Adaptation Syndrome, zero gravity sickness. A case is drawn for the necessity to apply a methodological approach that incorporates: (1) standardization of parameters in relation to the individual differences in variability and prestimulus levels; (2) a concern for patterning of responses; and (3) the physiological association with subjective reports. Vasomotor, heart rate, respiration rate, skin conductance and subjective reports of malaise were collected from 22 subjects while participating in three motion stressors; vertical acceleration, Coriolis stimulation, and combined optokinetic and Coriolis stimulation. The results demonstrate that ANS response patterns can be separated into three mutually exclusive components: (1) a generalized response to motion sickness; (2) a stimulus specific response to the type of stressor being presented; and (3) individualized stereotypical response patterns that are associated with subjective reports of malaise.

Morgan, M. G.↗

NASA NTRS1994

The Influence of Gravito-Inertial Force on Sensorimotor Integration and Reflexive Responses

Sensorimotor responses (e.g.. eye movements, spinal reflexes, etc depend upon the interpretation of the neural signals from the sensory systems. Since neural signals from the otoliths may represent either tilt (gravity) or translation (linear inertial force), sensory signals from the otolith organs are necessarily somewhat ambiguous. Therefore. the neural responses to changing otolith signals depend upon the context of the stimulation (e.g- active vs. passive, relative orientation of gravity, etc.) as well as upon other sensory signals (e.g., vision. canals, etc.). This session will focus upon the -role -played by the sensory signals from the otolith organs in producing efficient sensorimotor and behavioral responses. Curthoys will show the influence of the peripheral anatomy and physiology. Tomko will discuss the influence of tilt and translational otolith signals on eye movements. Merfeld will demonstrate the rate otolith organs play during the interaction of sensory signals from the canals and otoliths. Watt will show the influence of the otoliths on spinal/postural responses. Guedry will discuss the contribution of vestibular information to "path of movement"' perception and to the development of a stable vertical reference. Sensorimotor responses to the ambiguous inertial force stimulation provide an important tool to investigate how the nervous system processes patterns of sensory information and yields functional sensorimotor responses.

Curthoys, Ian S.↗

NASA NTRS2002

Baroreflex buffering and susceptibility to vasoactive drugs

BACKGROUND: The overall effect of vasoactive drugs on blood pressure is determined by a combination of the direct effect on vascular tone and an indirect baroreflex-mediated effect, a baroreflex buffering of blood pressure. Differences in baroreflex function affect the responsiveness to vasoactive medications, particularly baroreflex buffering of blood pressure; however, the magnitude is not known. METHODS AND RESULTS: We characterized baroreflex function and responses to vasoactive drugs in patients with idiopathic orthostatic intolerance, patients with essential hypertension, patients with monogenic hypertension and brachydactyly, patients with multiple system atrophy, and control subjects. We used phenylephrine sensitivity during ganglionic blockade as a measure of baroreflex buffering. Phenylephrine (25 microg) increased systolic blood pressure 6+/-1.6 mm Hg in control subjects, 6+/-1.1 mm Hg in orthostatic intolerance patients, 18+/-3.9 mm Hg in patients with essential hypertension, 31+/-3.4 mm Hg in patients with monogenic hypertension, and 25+/-3.4 mm Hg in patients with multiple system atrophy. Similar differences in sensitivities between groups were observed with nitroprusside. The sensitivity to vasoactive drugs was highly correlated with baroreflex buffering function and to a lesser degree with baroreflex control of heart rate. In control subjects, sensitivities to nitroprusside and phenylephrine infusions were correlated with baroreflex heart rate control and sympathetic nerve traffic. CONCLUSIONS: Our findings are consistent with an important effect of baroreflex blood pressure buffering on the sensitivity to vasoactive drugs. They suggest that even moderate changes in baroreflex function may have a substantial effect on the sensitivity to vasoactive medications.

NASA Discipline Regulatory Physiology↗

NASA NTRS2007

Sensorimotor Adaptation Following Exposure to Ambiguous Inertial Motion Cues

The central nervous system must resolve the ambiguity of inertial motion sensory cues in order to derive accurate spatial orientation awareness. Adaptive changes in how inertial cues from the otolith system are integrated with other sensory information lead to perceptual and postural disturbances upon return to Earth s gravity. The primary goals of this ground-based research investigation are to explore physiological mechanisms and operational implications of tilt-translation disturbances during and following re-entry, and to evaluate a tactile prosthesis as a countermeasure for improving control of whole-body orientation during tilt and translation motion.

Wood, S. J.↗

NASA NTRS2002

Increased sympathetic activation in idiopathic orthostatic intolerance: role of systemic adrenoreceptor sensitivity

Idiopathic orthostatic intolerance (OI) is characterized by adrenergic symptoms with standing. Changes in central sympathetic tone or in adrenoreceptor sensitivity could contribute to this syndrome. In OI patients and control subjects, we determined heart rate (HR) and systolic blood pressure (SBP) changes after incremental bolus doses of isoproterenol and phenylephrine before and during ganglionic blockade with trimethaphan. SBP decreased by 17+/-1.6 mm Hg in patients and 3.9+/-3.8 mm Hg in control subjects (P<0.01) with trimethaphan. Patients with a larger decrease (28+/-3.8 mm Hg, n=7) in SBP with trimethaphan had greater supine SBP and supine and upright plasma norepinephrine levels than did patients with a lesser decrease (3.0+/-3.0 mm Hg, n=7) in SBP. Supine and orthostatic HRs were similar for the groups. The majority of patients had a normal HR response to isoproterenol before and during ganglionic blockade. Phenylephrine increased SBP similarly in patients and control subjects before and during blockade. Sympathetic support is increased in a subgroup of OI patients. Hyperadrenergic and nonhyperadrenergic subgroups have similar degrees of orthostatic tachycardia. Our findings suggest that the hyperadrenergic features of OI cannot be completely explained by systemic hypersensitivity of postsynaptic alpha(1)- and beta-adrenoreceptors but rather originates in enhanced sympathetic activation.

Non-NASA Center↗

NASA NTRSDate not supplied

Neurobiological Outcomes of Mice Exposed to Combined Spaceflight Stressors

As NASA plans for exploration beyond Low-Earth Orbit, it is imperative to understand how deep spaceflight stressors impact human physiology. Deep space exposes crew members to multiple NASA-defined risks, including altered gravity, ionizing radiation, and social isolation. While the effects of individual stressors have been studied, there are still gaps in our understanding of their combined effects. In this study, we utilized the simulated five-ion galactic cosmic radiation (GCR) and isolation to assess the combinatorial effects of space stressors on the central nervous system (CNS) in mice. Our study captures sexually dimorphic responses by quantifying CNS outcomes in crewage-matched male and female mice. We assessed CNS responses in mice exposed to four days of isolation, followed by three different dosage of acute radiation exposure (5 cGy, 15 cGy, and 50 cGy 5-ion GCRsim). Comprehensive hippocampal cytokine biomarker analyses were conducted in both males and females at two weeks post-irradiation (intermediate cohort) and 124 days post-irradiation (delayed cohort). Proteomics on hippocampal lysates were conducted in the delayed cohort. Our results provide evidence for sex-specific differentially regulated hippocampal cytokines and proteomic profiles. Immunohistochemical analysis of the mice brain from intermediate and delayed cohorts is currently underway for multiple protein markers, including microglial activation, astrocytes, and dopaminergic neuronal population, among others. This project closely aligns with NASA’s efforts to characterize sex-specific risks associated with deep space exploration. We anticipate the results from this project will aid in our understanding of spaceflight stressors to ensure crew health and performance.

spaceflight↗

NASA NTRS1994

The value of electrical stimulation as an exercise training modality

Voluntary exercise is the traditional way of improving performance of the human body in both the healthy and unhealthy states. Physiological responses to voluntary exercise are well documented. It benefits the functions of bone, joints, connective tissue, and muscle. In recent years, research has shown that neuromuscular electrical stimulation (NMES) simulates voluntary exercise in many ways. Generically, NMES can perform three major functions: suppression of pain, improve healing of soft tissues, and produce muscle contractions. Low frequency NMES may gate or disrupt the sensory input to the central nervous system which results in masking or control of pain. At the same time NMES may contribute to the activation of endorphins, serotonin, vasoactive intestinal polypeptides, and ACTH which control pain and may even cause improved athletic performances. Soft tissue conditions such as wounds and inflammations have responded very favorably to NMES. NMES of various amplitudes can induce muscle contractions ranging from weak to intense levels. NMES seems to have made its greatest gains in rehabilitation where directed muscle contractions may improve joint ranges of motion correct joint contractures that result from shortening muscles; control abnormal movements through facilitating recruitment or excitation into the alpha motoneuron in orthopedically, neurologically, or healthy subjects with intense sensory, kinesthetic, and proprioceptive information; provide a conservative approach to management of spasticity in neurological patients; by stimulation of the antagonist muscle to a spastic muscle stimulation of the agonist muscle, and sensory habituation; serve as an orthotic substitute to conventional bracing used with stroke patients in lieu of dorsiflexor muscles in preventing step page gait and for shoulder muscles to maintain glenohumeral alignment to prevent subluxation; and of course NMES is used in maintaining or improving the performance or torque producing capability of muscle. NMES in exercise training is our major concern.

Currier, Dean P.↗

NASA NTRS1996

Human physiology in space

The universality of gravity (1 g) in our daily lives makes it difficult to appreciate its importance in morphology and physiology. Bone and muscle support systems were created, cellular pumps developed, neurons organised and receptors and transducers of gravitational force to biologically relevant signals evolved under 1g gravity. Spaceflight provides the only microgravity environment where systematic experimentation can expand our basic understanding of gravitational physiology and perhaps provide new insights into normal physiology and disease processes. These include the surprising extent of our body's dependence on perceptual information, and understanding the effect and importance of forces generated within the body's weightbearing structures such as muscle and bones. Beyond this exciting prospect is the importance of this work towards opening the solar system for human exploration. Although both appear promising, we are only just beginning to taste what lies ahead.

NASA Center HQS↗

NASA NTRS1975

The auditory neural network in man

The principles of anatomy and physiology necessary for understanding brain wave recordings made from the scalp of normal people are briefly discussed. Brain waves evoked by sounds are described and certain of their features are related to the physical aspects of the stimulus and to the psychological state of the listener. The position is taken that data obtained through scalp probes can reveal a large amount of detail about brain functioning and that analysis of such records enable detection of the response of the nervous system to an acoustic message at the moment of its inception and to the progress of the message through the brain. Brain events responsible for distinguishing between similar signals and making decisions about them appear to generate characteristic and identifiable electrical waves. Some theoretical speculation about these data are introduced with the aim of generating a more heuristic model of the functioning brain.

Galambos, R.↗