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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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All sourcesNASA NTRSDOE OSTI
NASA NTRS1995

Radiogenic cell transformation and carcinogenesis

Radiation carcinogenesis is one of the major biological effects considered important in the risk assessment for space travel. Various biological model systems, including both cultured cells and animals, have been found useful for studying the carcinogenic effects of space radiations, which consist of energetic electrons, protons and heavy ions. The development of techniques for studying neoplastic cell transformation in culture has made it possible to examine the cellular and molecular mechanisms of radiation carcinogenesis. Cultured cell systems are thus complementary to animal models. Many investigators have determined the oncogenic effects of ionizing and nonionizing radiation in cultured mammalian cells. One of the cell systems used most often for radiation transformation studies is mouse embryonic cells (C3H10T1/2), which are easy to culture and give good quantitative dose-response curves. Relative biological effectiveness (RBE) for heavy ions with various energies and linear energy transfer (LET) have been obtained with this cell system. Similar RBE and LET relationship was observed by investigators for other cell systems. In addition to RBE measurements, fundamental questions on repair of sub- and potential oncogenic lesions, direct and indirect effect, primary target and lesion, the importance of cell-cell interaction and the role of oncogenes and tumor suppressor genes in radiogenic carcinogenesis have been studied, and interesting results have been found. Recently several human epithelial cell systems have been developed, and ionizing radiation have been shown to transform these cells. Oncogenic transformation of these cells, however, requires a long expression time and/or multiple radiation exposures. Limited experimental data indicate high-LET heavy ions can be more effective than low-LET radiation in inducing cell transformation. Cytogenetic and molecular analyses can be performed with cloned transformants to provide insights into basic genetic mechanism(s) of radiogenic transformation of human epithelial cells.

NASA Discipline Radiation Health↗
DOE OSTI2021

Quantitative cross-species translators of cardiac myocyte electrophysiology: Model training, experimental validation, and applications

Animal experimentation is key in the evaluation of cardiac efficacy and safety of novel therapeutic compounds. However, interspecies differences in the mechanisms regulating excitation-contraction coupling can limit the translation of experimental findings from animal models to human physiology and undermine the assessment of drugs’ efficacy and safety. Here, we built a suite of translators for quantitatively mapping electrophysiological responses in ventricular myocytes across species. We trained these statistical operators using a broad dataset obtained by simulating populations of our biophysically detailed computational models of action potential and Ca 2+ transient in mouse, rabbit, and human. We then tested our translators against experimental data describing the response to stimuli, such as ion channel block, change in beating rate, and β-adrenergic challenge. We demonstrate that this approach is well suited to predicting the effects of perturbations across different species or experimental conditions and suggest its integration into mechanistic studies and drug development pipelines.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2023

Applicability of the Nasa Galactic Cosmic Ray Simulator for Mice, Rats, and Minipigs

Space radiation poses multiple health risks to astronauts including cancer, cardiovascular disease, and damage to the central nervous system. Radiation from galactic cosmic rays (GCR) is the main source of these risks for missions beyond low Earth orbit to the moon and beyond. A galactic cosmic ray simulator (GCRsim) was developed at the NASA Space Radiation Laboratory to better understand and mitigate these risks by simulating the complex mixed field of the GCR environment at a ground-based facility. The GCRsim delivers a radiation field to cell and animal models in a laboratory setting that is comparable to the shielded radiation environment within internal organs of astronauts in deep space missions. Previous verification studies using Monte Carlo simulations with mouse (Digimouse) and rat (Digirat) digital phantoms showed that the GCRsim yields acceptable dose homogeneity within the internal organs of these animals. Spectral characteristics of the intended space radiation environment are also accurately reproduced at radiosensitive sites in both phantoms. In this work, similar Monte Carlo simulations were performed in a minipig model (Digipig) to show the applicability and limitations of the current GCRsim for larger animal model systems. The results showed dose homogeneity in internal organs of the three animal models with GCRsim irradiation. While slightly lower average doses were seen in the minipig compared to the external beam dose, the individual voxel doses in slices of the phantoms were found to be within 6%–8% of the average voxel dose, establishing that the GCRsim can still provide a relatively homogeneous irradiation within larger animals. Furthermore, simulated dose and fluence spectral results across the relevant linear energy transfer (LET) range agreed well with the reference field in the most relevant regions of the spectra, further verifying that the GCRsim beam represents the reference field in larger animals.

Galactic cosmic rays↗
NASA NTRSDate not supplied

The Potential Outcome Model: Explaining Low-Dose Radiobiology through an Epidemiologic Lens

One of the major challenges in understanding space radiation-induced carcinogenesis is the uncertainty from translating radiobiological research in cellular and animal models to humans, especially at doses below 100 mSv. Biological studies have shown a host of potential outcomes at lowdoses in animal and cellular models. The existence of non-targeted effects as bystander and abscopal effects is well-documented from clinical research and basic science1,2,3. While some studies have shown increased effects at low doses, others have shown evidence of hormetic bystander effects, where radiation exposure may be beneficial4,5,6. Despite these varied and diverse findings, epidemiologic studies largely support the linear-no threshold (LNT) assumption used by radiation protection guidance7,8. Translational animal-to-human models have predominantly considered ratio values such as the relative biological effectiveness (RBE) and dose and dose-rate effectiveness factor (DDREF) that rely on the assumption of LNT rather than implementing specific dose-response shapes in the low-dose region, and translational cell-to-human models are uncommon. The sufficient component cause model presents an opportunity to examine biological findings at low doses from an epidemiological lens9. In this model, exposures “sufficient” to cause an outcome of interest are presented in pie charts, such that when all slices of a pie chart are fulfilled, the outcome will occur. Multiple pie charts may exist for a single outcome, illustrating individual differences9. In 1988,Greenland and Poole adapted the sufficient component cause model to incorporate interaction with other exposures (such as genetics or lifestyle factors)10. They show that a range of biological processes are possible in a population, but that an epidemiologic study will only reveal the mean outcome from the population at large10,11. Using this construct, the multiple outcomes presented in radiobiological models to date can be explained in the context of epidemiologic studies. This presentation aims to demonstrate a causal framework that can integrate radiobiological and epidemiological models to date. It is intended as a conversation starter to spur future research.

C M Milder↗
NASA NTRSDate not supplied

The Sufficient Component Cause Model Explaining Low-Dose Radiobiology through an Epidemiologic Lens

One of the major challenges in understanding space radiation-induced carcinogenesis is the uncertainty from translating radiobiological research in cellular and animal models to humans, especially at doses below 100 mSv. Biological studies have shown a host of potential outcomes at low doses in animal and cellular models. The existence of non-targeted effects as bystander and abscopal effects is well-documented from clinical research and basic science1,2,3. While some studies have shown increased effects at low doses, others have shown evidence of hormetic bystander effects, where radiation exposure may be beneficial4,5,6. Despite these varied and diverse findings, epidemiologic studies largely support the linear-no threshold (LNT) assumption used by radiation protection guidance7,8. Translational animal-to-human models have predominantly considered ratio values such as the relative biological effectiveness (RBE) and dose and dose-rate effectiveness factor (DDREF) that rely on the assumption of LNT rather than implementing specific dose-response shapes in the low-dose region, and translational cell-to-human models are uncommon. The sufficient component cause model presents an opportunity to examine biological findings at low doses from an epidemiological lens9. In this model, exposures “sufficient” to cause an outcome of interest are presented in pie charts, such that when all slices of a pie chart are fulfilled, the outcome will occur. Multiple pie charts may exist for a single outcome, illustrating individual differences9. In 1988,Greenland and Poole adapted the sufficient component cause model to incorporate interaction with other exposures (such as genetics or lifestyle factors)10. They show that a range of biological processes are possible in a population, but that an epidemiologic study will only reveal the mean outcome from the population at large10,11. Using this construct, the multiple outcomes presented in radiobiological models to date can be explained in the context of epidemiologic studies. This presentation aims to demonstrate a causal framework that can integrate radiobiological and epidemiological models to date. It is intended as a conversation starter to spur future research.

C M Milder↗
NASA NTRS2004

Effects of heavy ions on visual function and electrophysiology of rodents: the ALTEA-MICE project

ALTEA-MICE will supplement the ALTEA project on astronauts and provide information on the functional visual impairment possibly induced by heavy ions during prolonged operations in microgravity. Goals of ALTEA-MICE are: (1) to investigate the effects of heavy ions on the visual system of normal and mutant mice with retinal defects; (2) to define reliable experimental conditions for space research; and (3) to develop animal models to study the physiological consequences of space travels on humans. Remotely controlled mouse setup, applied electrophysiological recording methods, remote particle monitoring, and experimental procedures were developed and tested. The project has proved feasible under laboratory-controlled conditions comparable in important aspects to those of astronauts' exposure to particle in space. Experiments are performed at the Brookhaven National Laboratories [BNL] (Upton, NY, USA) and the Gesellschaft fur Schwerionenforschung mbH [GSI]/Biophysik (Darmstadt, FRG) to identify possible electrophysiological changes and/or activation of protective mechanisms in response to pulsed radiation. Offline data analyses are in progress and observations are still anecdotal. Electrophysiological changes after pulsed radiation are within the limits of spontaneous variability under anesthesia, with only indirect evidence of possible retinal/cortical responses. Immunostaining showed changes (e.g. increased expression of FGF2 protein in the outer nuclear layer) suggesting a retinal stress reaction to high-energy particles of potential relevance in space. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

NASA Center JSC↗
NASA NTRS1983

The first dedicated life sciences mission - Spacelab 4

The details of the payload and the experiments in Spacelab 4, the first Spacelab mission dedicated entirely to the life sciences, are discussed. The payload of Spacelab 4, carried in the bay of the Shuttle Orbiter, consists of 25 tentatively selected investigations combined into a comprehensive integrated exploration of the effects of acute weightlessness on living systems. The payload contains complementary designs in the human and animal investigations in order to validate animal models of human physiology in weightlessness. Animals used as experimental subjects will include squirrel monkeys, laboratory rats, several species of plants, and frog eggs. The main scientific objectives of the investigations include the study of the acute cephalic fluid shift, cardiovascular adaptation to weightlessness, including postflight reductions in orthostatic tolerance and exercise capacity, and changes in vestibular function, including space motion sickness, associated with weightlessness. Other scientific objective include the study of red cell mass reduction, negative nitrogen balance, altered calcium metabolism, suppressed in vitro lymphocyte reactivity, gravitropism and photropism in plants, and fertilization and early development in frog eggs.

Cramer, D. R.↗
NASA NTRS1991

Effects of suspension-induced osteopenia on the mechanical behaviour of mouse long bones

Whereas most studies of tail-suspension induced osteopenia have utilized rat femora, the present study investigated the effects of a 14 day tail-suspension on the mechanical behaviour of mice femora, tibiae and humeri. Force-deflection properties were obtained via three-point bending for long bones from suspended and control mice. Whole bone behaviour was characterized by converting the force-deflection values to stiffness, strength, ductility and energy parameters which were not normalized for specimen geometry. The effects of a systematic variation in the deflection rate over the range 0.1-10 mm min-1 were also evaluated. Statistical analysis indicated that the primary effect of the tail-suspension period was lowered bone mass which was manifested mechanically through lower values of the bone strength parameters. These effects were similar in the bones of both the fore and hind limbs. The results also demonstrated that the stiffness, ductility and energy characteristics were much less influenced by the tail-suspension. Whereas a significant dependence of the bone strength values upon deflection rate was observed for the femora and humeri, the other mechanical parameters were less sensitive. Based upon the nature of the physical and mechanical changes observed in the long bones following tail-suspension, the mouse appears to be a suitable animal model for the study of osteopenia.

NASA Discipline Number 93-10↗
NASA NTRS2001

Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis

Intracellular calcium is increased in vulnerable spinal motoneurons in immune-mediated as well as transgenic models of amyotrophic lateral sclerosis (ALS). To determine whether intracellular calcium levels are influenced by the calcium-binding protein parvalbumin, we developed transgenic mice overexpressing parvalbumin in spinal motoneurons. ALS immunoglobulins increased intracellular calcium and spontaneous transmitter release at motoneuron terminals in control animals, but not in parvalbumin overexpressing transgenic mice. Parvalbumin transgenic mice interbred with mutant SOD1 (mSOD1) transgenic mice, an animal model of familial ALS, had significantly reduced motoneuron loss, and had delayed disease onset (17%) and prolonged survival (11%) when compared with mice with only the mSOD1 transgene. These results affirm the importance of the calcium binding protein parvalbumin in altering calcium homeostasis in motoneurons. The increased motoneuron parvalbumin can significantly attenuate the immune-mediated increases in calcium and to a lesser extent compensate for the mSOD1-mediated 'toxic-gain-of-function' in transgenic mice.

Non-NASA Center↗
DOE OSTI2020

MicroRNAs as disease progression biomarkers and therapeutic targets in experimental autoimmune encephalomyelitis model of multiple sclerosis

Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain, spinal cord and optic nerve leading to demyelination. Focal demyelination is associated with relapsing-remitting multiple sclerosis, while progressive forms of the disease show axonal degeneration and neuronal loss. The tests currently used in the clinical diagnosis and management of multiple sclerosis have limitations due to specificity and sensitivity. MicroRNAs (miRNAs) are dysregulated in many diseases and disorders including demyelinating and neuroinflammatory diseases. A review of recent studies with the experimental autoimmune encephalomyelitis animal model (mostly female mice 6–12 weeks of age) has confirmed miRNAs as biomarkers of experimental autoimmune encephalomyelitis disease and importantly at the pre-onset (asymptomatic) stage when assessed in blood plasma and urine exosomes, and spinal cord tissue. The expression of certain miRNAs was also dysregulated at the onset and peak of disease in blood plasma and urine exosomes, brain and spinal cord tissue, and at the post-peak (chronic) stage of experimental autoimmune encephalomyelitis disease in spinal cord tissue. Therapies using miRNA mimics or inhibitors were found to delay the induction and alleviate the severity of experimental autoimmune encephalomyelitis disease. Interestingly, experimental autoimmune encephalomyelitis disease severity was reduced by overexpression of miR-146a, miR-23b, miR-497, miR-26a, and miR-20b, or by suppression of miR-182, miR-181c, miR-223, miR-155, and miR873. Further studies are warranted on determining more fully miRNA profiles in blood plasma and urine exosomes of experimental autoimmune encephalomyelitis animals since they could serve as biomarkers of asymptomatic multiple sclerosis and disease course. Additionally, studies should be performed with male mice of a similar age, and with aged male and female mice.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2000

Adaptive plasticity in vestibular influences on cardiovascular control

Data collected in both human subjects and animal models indicate that the vestibular system influences the control of blood pressure. In animals, peripheral vestibular lesions diminish the capacity to rapidly and accurately make cardiovascular adjustments to changes in posture. Thus, one role of vestibulo-cardiovascular influences is to elicit changes in blood distribution in the body so that stable blood pressure is maintained during movement. However, deficits in correcting blood pressure following vestibular lesions diminish over time, and are less severe when non-labyrinthine sensory cues regarding body position in space are provided. These observations show that pathways that mediate vestibulo-sympathetic reflexes can be subject to plastic changes. This review considers the adaptive plasticity in cardiovascular responses elicited by the central vestibular system. Recent data indicate that the posterior cerebellar vermis may play an important role in adaptation of these responses, such that ablation of the posterior vermis impairs recovery of orthostatic tolerance following subsequent vestibular lesions. Furthermore, recent experiments suggest that non-labyrinthine inputs to the central vestibular system may be important in controlling blood pressure during movement, particularly following vestibular dysfunction. A number of sensory inputs appear to be integrated to produce cardiovascular adjustments during changes in posture. Although loss of any one of these inputs does not induce lability in blood pressure, it is likely that maximal blood pressure stability is achieved by the integration of a variety of sensory cues signaling body position in space.

Non-NASA Center↗
NASA NTRS1996

Laparoscopic surgery in weightlessness

BACKGROUND: Performing a surgical procedure in weightlessness has been shown not to be any more difficult than in a 1g environment if the requirements for the restraint of the patient, operator, and surgical hardware are observed. The feasibility of performing a laparoscopic surgical procedure in weightlessness, however, has been questionable. Concerns have included the impaired visualization from the lack of gravitational retraction of the bowel and from floating debris such as blood. METHODS: In this project, laparoscopic surgery was performed on a porcine animal model in the weightlessness of parabolic flight. RESULTS: Visualization was unaffected due to the tethering of the bowel by the elastic mesentery and the strong tendency for debris and blood to adhere to the abdominal wall due to surface tension forces. CONCLUSIONS: There are advantages to performing a laparoscopic instead of an open surgical procedure in a weightless environment. These will become important as the laparoscopic support hardware is miniaturized from its present form, as laparoscopic technology becomes more advanced, and as more surgically capable crew medical officers are present in future long-duration space-exploration missions.

manned↗
DOE OSTI2021

Targeted metabolomic analysis identifies increased serum levels of GABA and branched chain amino acids in canine diabetes

Introduction Dogs with naturally occurring diabetes mellitus represent a potential model for human type 1 diabetes, yet signifcant knowledge voids exist in terms of the pathogenic mechanisms underlying the canine disorder. Untargeted metabolomic studies from a limited number of diabetic dogs identifed similarities to humans with the disease. Objective To expand and validate earlier metabolomic studies, identify metabolites that difer consistently between diabetic and healthy dogs, and address whether certain metabolites might serve as disease biomarkers. Methods Untargeted metabolomic analysis via liquid chromatography-mass spectrometry was performed on serum from diabetic (n=15) and control (n=15) dogs. Results were combined with those of our previously published studies using identical methods (12 diabetic and 12 control dogs) to identify metabolites consistently diferent between the groups in all 54 dogs. Thirty-two candidate biomarkers were quantifed using targeted metabolomics. Biomarker concentrations were compared between the groups using multiple linear regression (corrected P<0.0051 considered signifcant). Results Untargeted metabolomics identifed multiple persistent diferences in serum metabolites in diabetic dogs compared with previous studies. Therefore, targeted metabolomics showed increases in gamma amino butyric acid, valine, leucine, isoleucine, citramalate, and 2-hydroxyisobutyric acid in diabetic versus control dogs while indoxyl sulfate, N-acetyl-L-aspartic acid, kynurenine, anthranilic acid, tyrosine, glutamine, and tauroursodeoxycholic acid were decreased. Conclusion Several of these fndings parallel metabolomic studies in both human diabetes and other animal models of this disease. Given recent studies on the role of GABA and branched chain amino acids in human diabetes, the increase in serum concentrations in canine diabetes warrants further study of these metabolites as potential biomarkers, and to identify similarity in mechanisms underlying this disease in humans and dogs.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2002

Quantitative analysis of aortic regurgitation: real-time 3-dimensional and 2-dimensional color Doppler echocardiographic method--a clinical and a chronic animal study

BACKGROUND: For evaluating patients with aortic regurgitation (AR), regurgitant volumes, left ventricular (LV) stroke volumes (SV), and absolute LV volumes are valuable indices. AIM: The aim of this study was to validate the combination of real-time 3-dimensional echocardiography (3DE) and semiautomated digital color Doppler cardiac flow measurement (ACM) for quantifying absolute LV volumes, LVSV, and AR volumes using an animal model of chronic AR and to investigate its clinical applicability. METHODS: In 8 sheep, a total of 26 hemodynamic states were obtained pharmacologically 20 weeks after the aortic valve noncoronary (n = 4) or right coronary (n = 4) leaflet was incised to produce AR. Reference standard LVSV and AR volume were determined using the electromagnetic flow method (EM). Simultaneous epicardial real-time 3DE studies were performed to obtain LV end-diastolic volumes (LVEDV), end-systolic volumes (LVESV), and LVSV by subtracting LVESV from LVEDV. Simultaneous ACM was performed to obtain LVSV and transmitral flows; AR volume was calculated by subtracting transmitral flow volume from LVSV. In a total of 19 patients with AR, real-time 3DE and ACM were used to obtain LVSVs and these were compared with each other. RESULTS: A strong relationship was found between LVSV derived from EM and those from the real-time 3DE (r = 0.93, P <.001, mean difference (3D - EM) = -1.0 +/- 9.8 mL). A good relationship between LVSV and AR volumes derived from EM and those by ACM was found (r = 0.88, P <.001). A good relationship between LVSV derived from real-time 3DE and that from ACM was observed (r = 0.73, P <.01, mean difference = 2.5 +/- 7.9 mL). In patients, a good relationship between LVSV obtained by real-time 3DE and ACM was found (r = 0.90, P <.001, mean difference = 0.6 +/- 9.8 mL). CONCLUSION: The combination of ACM and real-time 3DE for quantifying LV volumes, LVSV, and AR volumes was validated by the chronic animal study and was shown to be clinically applicable.

Validation Studies↗
DOE OSTI2022

Tissue replication and mucosal swab detection of Sosuga virus in Syrian hamsters in the absence of overt tissue pathology and clinical disease

Human infection with Sosuga virus (SOSV), a recently discovered pathogenic paramyxovirus, has been reported in one individual to date. No animal models of disease are currently available for SOSV. Here, we describe initial characterization of experimental infection in Syrian hamsters, including kinetics of virus dissemination and replication, and the corresponding clinical parameters, immunological responses, and histopathology. Here, we demonstrate susceptibility of hamsters to infection in the absence of clinical signs or significant histopathologic findings in tissues.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2003

Time course of epiphyseal growth plate fusion in rat tibiae

Although the rat is the most common animal model used in studying osteoporosis, it is often used inappropriately. Osteoporosis is a disease that most commonly occurs in humans long after growth plate fusion with the associated cessation of longitudinal bone growth, but there has been a question as to when or to what extent the rat growth plate fuses. To investigate this question, we used microcomputed X-ray tomography, at voxel resolutions ranging from (5.7 micro m)(3) to (11 micro m)(3), to image the proximal epiphyseal growth plates of both male (n = 19) and female (n = 15) rat tibiae, ranging in age from 2 to 25 months. The three-dimensional images were used to evaluate fusion of the epiphyseal growth plate by quantitating the amount of cancellous bone that has bridged across the growth plate. The results suggest that the time course of fusion of the epiphyseal growth plate follows a sigmoidal pattern, with 10% of the maximum number of bridges having formed by 3.9 months in the male tibiae and 5.8 months in the female tibiae, 50% of the maximum number of bridges having formed by 5.6 months in the male tibiae and 5.9 months in the female tibiae, and 90% of the total maximum of bridges have formed by 7.4 months for the males and 6.5 months for the females. The total volume of bridges per tibia at the age at which the maximum number of bridges per tibia has first formed is 0.99 mm(3)/tibia for the males and 0.40 mm(3)/tibia for the females. After the maximum number of bridges (-290 for females, -360 for males) have formed the total volume of bridges per tibia continues to increase for an additional 7.0 months in the males and 17.0 months for the females until they reach maximum values (-1.5 mm(3)/tibia for the males and -2.2 mm(3)/tibia for the females).

NASA Discipline Cell Biology↗
NASA NTRS2010

Vehicle Sketch Pad: a Parametric Geometry Modeler for Conceptual Aircraft Design

The conceptual aircraft designer is faced with a dilemma, how to strike the best balance between productivity and fidelity? Historically, handbook methods have required only the coarsest of geometric parameterizations in order to perform analysis. Increasingly, there has been a drive to upgrade analysis methods, but these require considerably more precise and detailed geometry. Attempts have been made to use computer-aided design packages to fill this void, but their cost and steep learning curve have made them unwieldy at best. Vehicle Sketch Pad (VSP) has been developed over several years to better fill this void. While no substitute for the full feature set of computer-aided design packages, VSP allows even novices to quickly become proficient in defining three-dimensional, watertight aircraft geometries that are adequate for producing multi-disciplinary meta-models for higher order analysis methods, wind tunnel and display models, as well as a starting point for animation models. This paper will give an overview of the development and future course of VSP.

Hahn, Andrew S.↗
NASA NTRS2015

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.↗