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Neurophysiological model of the normal and abnormal human pupil

Anatomical, experimental, and computer simulation studies were used to determine the structure of the neurophysiological model of the pupil size control system. The computer simulation of this model demonstrates the role played by each of the elements in the neurological pathways influencing the size of the pupil. Simulations of the effect of drugs and common abnormalities in the system help to illustrate the workings of the pathways and processes involved. The simulation program allows the user to select pupil condition (normal or an abnormality), specific site along the neurological pathway (retina, hypothalamus, etc.) drug class input (barbiturate, narcotic, etc.), stimulus/response mode, display mode, stimulus type and input waveform, stimulus or background intensity and frequency, the input and output conditions, and the response at the neuroanatomical site. The model can be used as a teaching aid or as a tool for testing hypotheses regarding the system.

Krenz, W.↗

Use of animal models for space flight physiology studies, with special focus on the immune system

Animal models have been used to study the effects of space flight on physiological systems. The animal models have been used because of the limited availability of human subjects for studies to be carried out in space as well as because of the need to carry out experiments requiring samples and experimental conditions that cannot be performed using humans. Experiments have been carried out in space using a variety of species, and included developmental biology studies. These species included rats, mice, non-human primates, fish, invertebrates, amphibians and insects. The species were chosen because they best fit the experimental conditions required for the experiments. Experiments with animals have also been carried out utilizing ground-based models that simulate some of the effects of exposure to space flight conditions. Most of the animal studies have generated results that parallel the effects of space flight on human physiological systems. Systems studied have included the neurovestibular system, the musculoskeletal system, the immune system, the neurological system, the hematological system, and the cardiovascular system. Hindlimb unloading, a ground-based model of some of the effects of space flight on the immune system, has been used to study the effects of space flight conditions on physiological parameters. For the immune system, exposure to hindlimb unloading has been shown to results in alterations of the immune system similar to those observed after space flight. This has permitted the development of experiments that demonstrated compromised resistance to infection in rodents maintained in the hindlimb unloading model as well as the beginning of studies to develop countermeasures to ameliorate or prevent such occurrences. Although there are limitations to the use of animal models for the effects of space flight on physiological systems, the animal models should prove very valuable in designing countermeasures for exploration class missions of the future.

Review↗

How the science and engineering of spaceflight contribute to understanding the plasticity of spinal cord injury

Space programs support experimental investigations related to the unique environment of space and to the technological developments from many disciplines of both science and engineering that contribute to space studies. Furthermore, interactions between scientists, engineers and administrators, that are necessary for the success of any science mission in space, promote interdiscipline communication, understanding and interests which extend well beyond a specific mission. NASA-catalyzed collaborations have benefited the spinal cord rehabilitation program at UCLA in fundamental science and in the application of expertise and technologies originally developed for the space program. Examples of these benefits include: (1) better understanding of the role of load in maintaining healthy muscle and motor function, resulting in a spinal cord injury (SCI) rehabilitation program based on muscle/limb loading; (2) investigation of a potentially novel growth factor affected by spaceflight which may help regulate muscle mass; (3) development of implantable sensors, electronics and software to monitor and analyze long-term muscle activity in unrestrained subjects; (4) development of hardware to assist therapies applied to SCI patients; and (5) development of computer models to simulate stepping which will be used to investigate the effects of neurological deficits (muscle weakness or inappropriate activation) and to evaluate therapies to correct these deficiencies.

Review↗

Diagnosis by integrating model-based reasoning with knowledge-based reasoning

Our research investigates how observations can be categorized by integrating a qualitative physical model with experiential knowledge. Our domain is diagnosis of pathologic gait in humans, in which the observations are the gait motions, muscle activity during gait, and physical exam data, and the diagnostic hypotheses are the potential muscle weaknesses, muscle mistimings, and joint restrictions. Patients with underlying neurological disorders typically have several malfunctions. Among the problems that need to be faced are: the ambiguity of the observations, the ambiguity of the qualitative physical model, correspondence of the observations and hypotheses to the qualitative physical model, the inherent uncertainty of experiential knowledge, and the combinatorics involved in forming composite hypotheses. Our system divides the work so that the knowledge-based reasoning suggests which hypotheses appear more likely than others, the qualitative physical model is used to determine which hypotheses explain which observations, and another process combines these functionalities to construct a composite hypothesis based on explanatory power and plausibility. We speculate that the reasoning architecture of our system is generally applicable to complex domains in which a less-than-perfect physical model and less-than-perfect experiential knowledge need to be combined to perform diagnosis.

Bylander, Tom↗

Studying Host-Pathogen Interactions In 3-D: Organotypic Models For Infectious Disease And Drug Development

Representative, reproducible and high-throughput models of human cells and tissues are critical for a meaningful evaluation of host-pathogen interactions and are an essential component of the research developmental pipeline. The most informative infection models - animals, organ explants and human trials - are not suited for extensive evaluation of pathogenesis mechanisms and screening of candidate drugs. At the other extreme, more cost effective and accessible infection models such as conventional cell culture and static co-culture may not capture physiological and three-dimensional aspects of tissue biology that are important in assessing pathogenesis, and effectiveness and cytotoxicity of therapeutics. Our lab has used innovative bioengineering technology to establish biologically meaningful 3-D models of human tissues that recapitulate many aspects of the differentiated structure and function of the parental tissue in vivo, and we have applied these models to study infectious disease. We have established a variety of different 3-D models that are currently being used in infection studies - including small intestine, colon, lung, placenta, bladder, periodontal ligament, and neuronal models. Published work from our lab has shown that our 3-D models respond to infection with bacterial and viral pathogens in ways that reflect the infection process in vivo. By virtue of their physiological relevance, 3-D cell cultures may also hold significant potential as models to provide insight into the neuropathogenesis of HIV infection. Furthermore, the experimental flexibility, reproducibility, cost-efficiency, and high throughput platform afforded by these 3-D models may have important implications for the design and development of drugs with which to effectively treat neurological complications of HIV infection.

Nickerson, Cheryl A.↗

Evaluating Effects of Altered Gravity on the Nervous System Using D. melanogaster

A comprehensive understanding of the effects of spaceflight and altered gravity on human physiology is necessary for continued human space exploration and long-term space habitation. The oxidative stress response has been identified in astronauts exposed to short- and long-term space missions that are exposed to the multitude of stress factors of spaceflight, including altered gravity and radiation exposure. Reactive oxygen species (ROS) are byproducts of homeostatic cellular metabolism, yet when overproduced the oxidative stress response ensues, rendering molecules destructive causing cell death and inflammation. Controlling aberrant ROS production is necessary to prevent pathological consequences, in particular within the nervous system, since neurons are extremely sensitive overexpressed ROS insults. We hypothesize that exposure to altered gravity triggers the oxidative stress response, leading to impairments in the nervous system. In this study, we used a well-established spaceflight model organism, Drosophila melanogaster, to assess altered gravity associated changes in the nervous system using a ground-based hypergravity model. Acute hypergravity resulted in an induction of oxidative stress-related genes with an increase in reactive oxygen species (ROS) in fly brains (p<0.001). Also, qPCR analysis shows that parkin gene expression is significantly reduced in these fly brains(p<0.05). Additionally, chronic hypergravity resulted in depressed locomotor phenotype in these flies (p<0.05) in conjunction to decreased dopaminergic neuron counts (p<0.0001) and increased apoptosis in these fly brains (p<0.0001). Further, assessment of neurological changes, including the neuronal architecture, synaptic integrity and genetic regulation caused by hypergravity conditions were noted. Overall, our results validate chronic hypergravity simulation as a behavioral model to study spaceflight effects, and oxidative stress pathway as a potential avenue for countermeasure development for astronauts undergoing short- and long-term missions and for neurodegenerative research on Earth.

Mhatre, Siddhita↗

Looking around: 35 years of oculomotor modeling

Eye movements have attracted an unusually large number of researchers from many disparate fields, especially over the past 35 years. The lure of this system stemmed from its apparent simplicity of description, measurement, and analysis, as well as the promise of providing a "window in the mind." Investigators in areas ranging from biological control systems and neurological diagnosis to applications in advertising and flight simulation expected eye movements to provide clear indicators of what the sensory-motor system was accomplishing and what the brain found to be of interest. The parallels between compensatory eye movements and perception of spatial orientation have been a subject for active study in visual-vestibular interaction, where substantial knowledge has accumulated through experiments largely guided by the challenge of proving or disproving model predictions. Even though oculomotor control has arguably benefited more from systems theory than any other branch of motor control, many of the original goals remain largely unfulfilled. This paper considers some of the promising potential benefits of eye movement research and compares accomplishments with anticipated results. Four topics are considered in greater detail: (i) the definition of oculomotor system input and output, (ii) optimization of the eye movement system, (iii) the relationship between compensatory eye movements and spatial orientation through the "internal model," and (iv) the significance of eye movements as measured in (outer) space.

Flight Experiment↗

Improving survival after tissue vaporization (Ebullism)

Exposure of unprotected humans to altitudes above 63,000 ft results in ebullism. Ebullism occurs when the vapor pressure of tissues is less than the ambient pressure and the tissues spontaneously 'boil'. This may result in rapid unconsciousness, cardiac vaporlock, pulmonary collapse, cerebral anoxia, and sometimes even death. Potential places for this include EVA accidents in space, aircraft experiencing rapid decompression at high altitudes with cabin or pressure suit failure, and accidents during pressure suit training exercises. The pathophysiology of ebullism was studied in the 40's to 60's using animal models. There is one report of a prolonged, unprotected human exposure and several anecdotal of unprotected short term exposures to near vacuum. In addition to pulmonary and neurologic concerns, unprotected exposure of the head may result in freezing of the corneal surface of the eye. Surface eye freezing may impair vision and significantly impact mission completion. At this time, little data are available on the effectiveness of conventional treatment protocols, such as hyperbaric oxygen, for ebullism induced injuries. Research is needed to assess the efficacy of other adjunctive therapies such as high frequency ventilation and cerebral protective drugs that are still under development.

Stegmann, Barbara J.↗

A Multi Targeted Dietary Supplement as a Potential Countermeasure for Prolonged, Deep Space Exploration

Deep space exploration, particularly to the Moon and Mars, are currently major goals of NASA and other international space agencies. Long-term space flight presents unique challenges to the human physiology from microgravity, social isolation, altered circadian rhythm and radiation. Oxidative stress has been implicated as a crucial factor in space environment induced injury. Elucidating these detrimental effects on the central nervous system and brain is a primary objective, as they may result in adverse changes in astronaut behavior, mood and performance of critical tasks. We were recently funded by HRP Human Factors Behavioral Performance (HFBP) Element to test the hypothesis that Galactic Cosmic Ray Simulation (GCRsim) Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure and function, and neurobehavioral and cognitive performance. This project will identify potential biomarkers for, and mechanisms underlying, structural and functional changes in the immune and nervous systems leading to behavioral/cognitive performance deficits, and its potential application to develop effective countermeasures to mitigate negative health effects of long duration space habitation. Countermeasures to offset neurological damaged and cognitive deficits are paramount for protecting astronauts during deep space transits, but many countermeasures have been found to be unsuitable in ground-based model studies. We have developed a multi targeted dietary supplement (MTDS) designed to simultaneously ameliorate oxidative stress, inflammatory processes, energetic shortfalls, and membrane and mitochondrial deterioration. Administration of this MTDS has improved cognition and longevity in age accelerated and normal aging mice. Specifically, the MTDS was found to prevent a decline in mitochondrial complex III activity and cell loss, as well as prevent an increase in protein carbonyls and mitochondrial 3-nitrotyrosine in the brain of these mice. Further, administration of the MTDS was also found to reduce bone marrow chromosomal aberrations, DNA damage, lymphocyte apoptosis after whole body exposure of 2 Gy γ radiation. Mice exposed to a high dose cranially (10 Gy) had decreased cognitive responses (seen as increased latency time to uncover buried food and decreased novel object recognition), increased plasma 8-OHdG levels, increased markers of cell stress in the brain, decreased hippocampal brain-derived neurotrophic factor (BDNF) protein and decreased plasma levels of cytokines, all of which were ameliorated with treatment of the MTDS. As we have shown the supplement is protective in models of cognitive damage similar space environment stressors, particularly increased oxidative stress, we propose it may be a suitable countermeasure for upcoming deep space exploration.

radiation↗

A MULTI TARGETED DIETARY SUPPLEMENT AS A POTENTIAL COUNTERMEASURE FOR DEEP SPACE EXPLORATION

Future deep space exploration to the Moon and Mars and beyond are currently major goals of NASA. Space flight presents unique challenges to the human physiology from the combined effects of microgravity, social isolation, altered circadian rhythm and radiation. Oxidative stress has been implicated as a crucial factor in space environment induced injury. Elucidating these detrimental effects on the central nervous system and brain is a primary objective, as they may result in adverse changes in astronaut behavior, mood and performance of critical tasks. We were recently funded by HRP Human Factors Behavioral Performance (HFBP) Element to test the hypothesis that Galactic Cosmic Ray Simulation (GCRsim) Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure and function, and neurobehavioral and cognitive performance. This project will identify potential biomarkers for, and mechanisms underlying, structural and functional changes in the immune and nervous systems leading to behavioral/cognitive performance deficits, and its potential application to develop effective countermeasures to mitigate negative health effects of long duration space habitation. Countermeasures to offset neurological damaged and cognitive deficits are paramount for protecting astronauts during deep space transits, but many countermeasures have been found to be unsuitable in ground-based model studies. We have developed a multi targeted dietary supplement (MTDS) designed to simultaneously ameliorate oxidative stress, inflammatory processes, energetic shortfalls, and membrane and mitochondrial deterioration. Administration of this MTDS has improved cognition and longevity in age accelerated and normal aging mice. Specifically, the MTDS was found to prevent a decline in mitochondrial complex III activity and cell loss, as well as prevent an increase in protein carbonyls and mitochondrial 3-nitrotyrosine in the brain of these mice. Further, administration of the MTDS was also found to reduce bone marrow chromosomal aberrations, DNA damage, lymphocyte apoptosis after whole body exposure of 2 Gy γ radiation. Mice exposed to a high dose cranially (10 Gy) had decreased cognitive responses (seen as increased latency time to uncover buried food and decreased novel object recognition), increased plasma 8-OHdG levels, increased markers of cell stress in the brain, decreased hippocampal brain-derived neurotrophic factor (BDNF) protein and decreased plasma levels of cytokines, all of which were ameliorated with treatment of the MTDS. As we have shown the supplement is protective in models of cognitive damage similar space environment stressors, particularly increased oxidative stress, we propose it may be a suitable countermeasure for upcoming deep space exploration.

Stephanie Puukila↗

Western Montana Ecological Forecasting II: Enhancing Habitat Suitability Modeling of Mustelid Species and Contaminant Monitoring in Northern Montana Using NASA Earth Observations

Environmental contaminants in aquatic ecosystems threaten both human and ecosystem health. Western Montana’s rivers possess great economic and ecological value, yet the status of contaminants in these systems can be unclear. Contaminants such as brominated flame-retardants, heavy metals, and pharmaceuticals negatively affect ecosystem health by traveling through the food chain and bioaccumulating in apex predators. Exposure to these contaminants can result in neurological, endocrine, and reproductive impairments in wildlife and humans. American mink (Neovison vison) and North American river otter (Lontra canadensis) have a predominantly aquatic diet and serve as reliable indicator species of environmental health. Working Dogs for Conservation (WD4C) uses detection dogs to locate scat samples of these species which are assessed for contaminants by the Virginia Institute of Marine Science (VIMS). With Software for Assisted Habitat Modeling (SAHM), the team generated current (2013-2020) and projected (2021-2040) habitat suitability models for mink and otter utilizing NASA Earth observations from Terra Moderate Resolution Imaging Spectroradiometer (MODIS), Global Precipitation Measurement Integrated Multi-Satellite Retrievals for GPM (GPM IMERG), Shuttle Radar Topography Mission (SRTM), and Soil Moisture Active Passive (SMAP). The habitat suitability maps’ study region encompassed Flathead National Forest and Blackfeet Indian Reservation. Additionally, the team created site accessibility and precipitation anomaly maps that display the viability of survey locations. The current habitat suitability models performed well (AUC-PR=0.88). The most important predictor variables for suitable habitat were distance to rivers, elevation, and land cover. These end products will further inform WD4C survey site selection and contaminant monitoring.

Chelsea Morton↗

The cerebral hemodynamics of normotensive hypovolemia during lower-body negative pressure

Although severe hypovolemia can lead to hypotension and neurological decline, many patients with neurosurgical disorders experience a significant hypovolemia while autonomic compensatory mechanisms maintain a normal blood pressure. To assess the effects of normotensive hypovolemia upon cerebral hemodynamics, transcranial Doppler ultrasound monitoring of 13 healthy volunteers was performed during graded lower-body negative pressure of up to -50 mm Hg, an accepted laboratory model for reproducing the physiological effects of hypovolemia. Middle cerebral artery flow velocity declined by 16% +/- 4% (mean +/- standard error of the mean) and the ratio between transcranial Doppler ultrasound pulsatility and systemic pulsatility rose 22% +/- 8%, suggesting cerebral small-vessel vasoconstriction in response to the sympathetic activation unmasked by lower-body negative pressure. This vasoconstriction may interfere with the autoregulatory response to a sudden fall in blood pressure, and may explain the common observation of neurological deficit during hypovolemia even with a normal blood pressure.

Non-NASA Center↗

Western Montana Ecological Forecasting: Modeling Habitat Suitability of Mustelid Species to Guide Detection Dog Surveys for Contaminants Monitoring, via Collected Scats in River Systems of Western Montana

Environmental contaminants are becoming increasingly prevalent in riverine ecosystems. The status of contaminants in western Montana’s relatively pristine river systems is largely unknown. Monitoring for heavy metals, brominated flame-retardants (BFRs), and pharmaceuticals is important due to their negative effects on ecosystems. Exposure to these contaminants can have significant endocrine, neurological, and reproductive effects. Contaminants easily travel up the food chain and bioaccumulate in apex predators. As predators with a largely aquatic diet, American mink (Mustela vison) and North American river otter (Lontra canadensis) serve as reliable indicator species of environmental health and the status of contaminants. Analysis of scat from these species is a noninvasive method to measure contaminant levels, and detection dogs from Working Dogs for Conservation (WD4C) have been used to locate these scat samples. To aid in the search of these samples, habitat suitability models were created for mink and otter for the years 2013-2020 and projected to 2040 using the random forest algorithm in the Software for Assisted Habitat Modeling (SAHM). Predictor variable data were acquired from Landsat 8 Operational Land Imager (OLI), Terra Moderate Resolution Imaging Spectroradiometer (MODIS), Global Precipitation Measurement Integrated Multi-satellite Retrievals for GPM (GPM IMERG), Shuttle Radar Topography Mission (SRTM), and Soil Moisture Active Passive (SMAP). Within these models, the most important variable for mink and otter habitat was distance to river. Suitable habitat also corresponded with emergent herbaceous land cover and deeper river locations. These habitat suitability models will inform sampling site section for further contaminant analysis.

Anna Winter↗

Harnessing Artificial Intelligence for Medical Diagnosis and Treatment During Space Exploration Missions

BACKGROUND The medical capabilities necessary for long-duration exploration missions (LDEMs) will differ tremendously from those currently available to crew medical officers (CMOs) on the International Space Station (ISS). Ground support will be more challenging due to distance-related communication delays and data transmission, and resource utilization must be optimized given limited ability for resupply. Clinical decision support systems (CDSSs) can help mitigate these limitations. The recent launch of generative artificial intelligence (AI) tools based upon large language models (LLM) support the creation of a smart assistant for onboard triage, diagnosis, and guided treatment of medical conditions during these missions. The Informing Mission Planning via Analysis of Complex Tradespaces (IMPACT) tool can help predict which clinical problems and outcomes are likely to occur for a design reference mission (DRM) and assist Medical Operations and systems engineering teams in creating a medical system that may optimally mitigate the predicted risks. The purpose of this study was to identify AI tools currently available or in development for the assistive diagnosis and care of medical conditions predicted for an extended duration Lunar mission. METHODS The 119 medical conditions currently built into the IMPACT suite were categorized into systems, and these diagnoses were used as keywords for our literature search. Using PubMed and Google Scholar, we performed a literature survey of AI tools applicable to these conditions. Article inclusion criteria included publication between the years 2017-2023, as the sentinel paper discussing the “selective attention” driving ChatGPT and other generative transformer models was published in June 2017. Where applicable, we reviewed only the top 1000 research articles (based on relevance) for each of the keywords/phrases. AI tools whose training sets were exclusive to a pediatric patient population were excluded. We also excluded any medical diagnostic tools (such as CT, MRI, mass spectrometry) or procedures (such as endoscopy, surgery) that are unlikely to be available during LDEMs due to mass and volume constraints, CMO knowledge, skills, and abilities, and/or inherent procedural risks. RESULTS Our survey highlighted several AI-driven tools for the triage, diagnosis, and management of those medical conditions highlighted by IMPACT. Selected publications for each medical condition were then screened for inclusion within ten systems-based categories including: general diagnostic tools (25), tools to diagnose and manage respiratory (40), dermatologic (34), neurologic (28), auditory and vestibular (30), ophthalmic (34), musculoskeletal (104), infection-associated (92), and gynecologic (19) conditions, as well as tools that could be deployed in the setting of trauma and emergency (34). CONCLUSIONS Numerous AI-driven tools were highlighted within this literature survey, ranging from chatbot assistants that triage knee pain to vision transformer models for diagnosis of ophthalmic conditions using ocular surface images captured with a mobile phone. Remaining challenges include optimizing connectivity and integration of existing and developing systems into the vehicles or habitats. Notably, findings from this survey could help guide the initial design of an all-encompassing, onboard medical AI assistant for use during future LDEMs.

R A Lacinski↗

Medical Devices Assess, Treat Balance Disorders

You may have heard the phrase as difficult as walking and chewing gum as a joking way of referring to something that is not difficult at all. Just walking, however, is not all that simple physiologically speaking. Even standing upright is an undertaking requiring the complex cooperation of multiple motor and sensory systems including vision, the inner ear, somatosensation (sensation from the skin), and proprioception (the sense of the body s parts in relation to each other). The compromised performance of any of these elements can lead to a balance disorder, which in some form affects nearly half of Americans at least once in their lifetimes, from the elderly, to those with neurological or vestibular (inner ear) dysfunction, to athletes with musculoskeletal injuries, to astronauts returning from space. Readjusting to Earth s gravity has a significant impact on an astronaut s ability to balance, a result of the brain switching to a different "model" for interpreting sensory input in normal gravity versus weightlessness. While acclimating, astronauts can experience headaches, motion sickness, and problems with perception. To help ease the transition and study the effects of weightlessness on the body, NASA has conducted many investigations into post-flight balance control, realizing this research can help treat patients with balance disorders on Earth as well. In the 1960s, the NASA-sponsored Man Vehicle Laboratory at the Massachusetts Institute of Technology (MIT) studied the effects of prolonged space flight on astronauts. The lab s work intrigued MIT doctoral candidate Lewis Nashner, who began conducting NASA-funded research on human movement and balance under the supervision of Dr. Larry Young in the MIT Department of Aeronautics and Astronautics. In 1982, Nashner s work resulted in a noninvasive clinical technique for assessing the cooperative systems that allow the body to balance, commonly referred to as computerized dynamic posturography (CDP). CDP employs a series of dynamic protocols to isolate and assess balance function deficiencies. The technology was based on Nashner s novel, engineering-inspired concept of balance as an adaptable collaboration between multiple sensory and motor systems. CDP proved useful not only for examining astronauts, but for anyone suffering from balance problems. Today, CDP is the standard medical tool for objectively evaluating balance control.

Source record↗

Life and Microgravity Sciences Spacelab Mission: Human Research Pilot Study

The Life Sciences, Microgravity Science and Spacelab Mission contains a number of human experiments directed toward identifying the functional, metabolic and neurological characteristics of muscle weakness and atrophy during space flight. To ensure the successful completion of the flight experiments, a ground-based pilot study, designed to mimic the flight protocols as closely as possible, was carried out in the head-down tilt bed rest model. This report records the rationales, procedures, preliminary results and estimated value of the pilot study, the first of its kind, for 12 of the 13 planned experiments in human research. The bed rest study was conducted in the Human Research Facility at Ames Research Center from July 11 - August 28, 1995. Eight healthy male volunteers performed the experiments before, during and after 17 days bed rest. The immediate purposes of this simulation were to integrate the experiments, provide data in a large enough sample for publication of results, enable investigators to review individual experiments in the framework of a multi-disciplinary study and relay the experience of the pilot study to the mission specialists prior to launch.

Arnaud, Sara B.↗

Activation of nuclear transcription factor-kappaB in mouse brain induced by a simulated microgravity environment

Microgravity induces inflammatory responses and modulates immune functions that may increase oxidative stress. Exposure to a microgravity environment induces adverse neurological effects; however, there is little research exploring the etiology of these effects resulting from exposure to such an environment. It is also known that spaceflight is associated with increase in oxidative stress; however, this phenomenon has not been reproduced in land-based simulated microgravity models. In this study, an attempt has been made to show the induction of reactive oxygen species (ROS) in mice brain, using ground-based microgravity simulator. Increased ROS was observed in brain stem and frontal cortex with concomitant decrease in glutathione, on exposing mice to simulated microgravity for 7 d. Oxidative stress-induced activation of nuclear factor-kappaB was observed in all the regions of the brain. Moreover, mitogen-activated protein kinase kinase was phosphorylated equally in all regions of the brain exposed to simulated microgravity. These results suggest that exposure of brain to simulated microgravity can induce expression of certain transcription factors, and these have been earlier argued to be oxidative stress dependent.

Non-NASA Center↗

Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are a documented concern for human exploration of space. Acute CNS risks include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

Nelson, Gregory A.↗