Results for “GALACTIC RADIATION” — Page 17

NASA NTRS1992

The Jodrell bank 'C' pulsar survey - A survey of the northern Galactic plane for rapidly rotating pulsars

Nearly 1500 sq deg of the northern Galactic plane were surveyed for rapidly rotating pulsars using the 76-m Lovell telescope. The sampling rate was such that there was sufficient nominal sensitivity to detect pulsars with periods as short as 0.6 ms. To overcome the effects of dispersion, scattering, and galactic background radiation, the high frequency of 1420 MHz was used to survey the inner Galaxy, while lower frequencies of 928 and 610 MHz were used for regions further from the Galactic center. PSR 1937 + 21 was detected in the survey, but no new pulsars were discovered. This is consistent with the results of other recent surveys and suggests that rapidly rotating, high-luminosity pulsars are not very common in the Galactic disk.

Biggs, J. D.↗

NASA NTRS2014

Human Space Exploration

The Mars probe, launched by India a few months ago, is on its way to Mars. At this juncture, it is appropriate to talk about the opportunities presented to us for the Human Exploration of Mars. I am planning to highlight some of the challenges to take humans to Mars, descend, land, stay, ascend and return home safely. The logistics of carrying the necessary accessories to stay at Mars will be delivered in multiple stages using robotic missions. The primary ingredients for human survival is air, water, food and shelter and the necessity to recycle the primary ingredients will be articulated. Humans have to travel beyond the van Allen radiation belt under microgravity condition during this inter‐planetary travel for about 6 months minimum one way. The deconditioning of human system under microgravity conditions and protection of humans from Galactic cosmic radiation during the travel should be taken into consideration. The multi‐disciplinary effort to keep the humans safe and functional during this journey will be addressed.

Jeevarajan, Antony↗

NASA NTRS2019

NASA’s Galactic Cosmic Ray Simulator at Brookhaven National Laboratory: Enabling Human Exploration Missions to the Moon and Mars

With exciting new Agency plans for a sustainable return to the moon, astronauts will once again leave earth’s protective magnetosphere only to endure higher levels of radiation from galactic cosmic rays (GCR) and the possibility of a large solar particle event (SPE). Gateway, lunar landers, and surface habitats will be designed to protect crew against SPE’s with vehicle optimization, storm shelter concepts, and/or active dosimetry; however, the ever-penetrating GCR will continue to pose the most significant health risks especially as lunar missions increase in duration and as NASA sets its aspirations on Mars. The primary risks of concern include epithelial carcinogenesis and leukemia, central nervous system effects resulting in potential in-mission cognitive or behavioral impairment and/or late neurological disorders, degenerative tissue effects including cataracts, circulatory and heart disease, as well as, potential immune system decrements impacting multiple aspects of crew health. Characterization and mitigation of these risks requires a significant reduction in the large biological uncertainties of chronic (low-dose rate) heavy ion exposures and the validation of countermeasures in a relevant space environment. NASA has developed the “GCR Simulator” at Brookhaven National Laboratory to generate a spectrum of ion beams that approximates the primary and secondary GCR field experienced at human organ locations within a deep-space vehicle. The majority of the dose is delivered from protons (~65-75%) and alpha particles (~10-20%) with heavier ions (Z≤3) contributing the remainder. The “GCR Simulator” exposes state-of-the art cellular and animal model systems to 33 sequential beams including 4 proton energies plus degrader, 4 helium energies plus degrader, and the five heavy ions of C, O, Si, Ti, and Fe. A polyethylene degrader is used with the 100 MeV/n H and He beams to provide a nearly continuous distribution of low energy particles. A 500 mGy exposure, delivering doses from each of the 33 beams, requires 75-90 minutes. To more closely simulate the low dose rates found in space, sequential field exposures can be divided into daily fractions over 2-4 weeks, with individual fractions as low as 0.1-0.2 mGy. In the large beam configuration (60 x 60 cm(exp 2)), 54 special housing cages can accommodate 2-3 mice each for a 70-75 min duration or ~15 individually housed rats. Emerging research results from our 2018 runs utilizing mixed heavy ion fields and protracted space exposures are forthcoming and deepen our understanding of the numerous health risks faced by our astronauts. This paper discusses NASA’s innovative technology solution for a ground-based GCR simulator at the NASA Space Radiation Laboratory to enable future exploration missions.

Lisa C Simonsen↗

NASA NTRS1991

Radiation protection for human missions to the Moon and Mars

Radiation protection assessments are performed for advanced Lunar and Mars manned missions. The Langley cosmic ray transport code and the nucleon transport code are used to quantify the transport and attenuation of galactic cosmic rays and solar proton flares through various shielding media. Galactic cosmic radiation at solar maximum and minimum, as well as various flare scenarios are considered. Propagation data for water, aluminum, liquid hydrogen, lithium hydride, lead, and lunar and Martian regolith (soil) are included. Shield thickness and shield mass estimates required to maintain incurred doses below 30 day and annual limits (as set for Space Station Freedom and used as a guide for space exploration) are determined for simple geometry transfer vehicles. On the surface of Mars, dose estimates are presented for crews with their only protection being the carbon dioxide atmosphere and for crews protected by shielding provided by Martian regolith for a candidate habitat.

Simonsen, Lisa C.↗

NASA NTRSDate not supplied

The Effects to Exposure of Simulated Spaceflight Radiation on Behavioral Health of Male and Female Mice

Exposure to space radiation is a principal consideration of spaceflight missions as risk is leveraged as time and dose—both expected to increase with future missions to the Moon, Mars, and beyond. Previous mission exposure levels, galactic cosmic radiation (GCR) and solar particle events (SPE), have been characterized as increased compared to those natural to Earth and are predicted to cause robust deficits at higher doses and longer durations. The cognitive health implications of this critical difference are understood as risks to mission and crew operations. We examined potential radiation-induced disruptions on brain health through resting-state in-cage behavior. 23–24-week-old male and female mice were exposed to 0 cGy (Sham), 5 cGy, 15 cGy, and 50 cGy via Five-Ion GCR Simulation (H, Si, He, O, Fe) at the NASA Space Radiation Lab in Brookhaven National Labs. Behavioral and cognitive performance were evaluated via frequency/duration of digging, rearing, and grooming within the 72-hour period immediately following irradiation. Additionally, during this time we evaluated nestlet building using a 5-stage Deacon score, rating shredding and shelter assembly of cotton material from untouched (1) to shredded and formed into a crater shape (5). We have observed differences in Deacon score only among the 15 cGy subset. Further comparative performance analysis will be completed evaluating the differences in irradiation effects between male and female mice. These experimental design aspects that allot for gender-inclusivity is supportive of the diversification of future space travel mission plans. Investigating gender differences is an element under our main objective of determining radiation dose-response curves. In brief, these studies identified a space-relevant radiation dose of 15 cGy that that can be utilized for future standardized ground studies on the nervous system.

spaceflight cognition impairment↗

NASA NTRSDate not supplied

Changes in Cognitive Performance and Behavior Induced by Space-like Environment

Exposure to space radiation is a principal consideration of spaceflight missions as risk is leveraged as time and dose—both expected to increase with future missions to the Moon, Mars, and beyond. Previous mission exposure levels, galactic cosmic radiation (GCR) and solar particle events (SPE), have been characterized as increased compared to those natural to Earth and are predicted to cause robust deficits at higher doses and longer durations. The cognitive health implications of this critical difference are understood as risks to mission and crew operations. We examined potential radiation-induced disruptions on brain health through resting-state in-cage behavior. 23–24-week-old male and female mice were exposed to 0 cGy (Sham), 5 cGy, 15 cGy, and 50 cGy via Five-Ion GCR Simulation (H, Si, He, O, Fe) at the NASA Space Radiation Lab in Brookhaven National Labs. Behavioral and cognitive performance were evaluated via frequency/duration of digging, rearing, and grooming within the 72-hour (acute) and 91-day (delayed) period following irradiation. Additionally, during this time we evaluated nestlet building using a 5-stage Deacon score, rating shredding and shelter assembly of cotton material from untouched (1) to shredded and formed into a crater shape (5). We have observed differences in behavior frequency and duration differences among the 15 cGy subset within the acute observation window. There were no significant differences in behavior frequencies nor duration during the delayed observation period. These experimental design aspects that allot for gender-inclusivity is supportive of the diversification of future space travel mission plans. Investigating gender differences is an element under our main objective of determining radiation dose-response curves. In brief, these studies identified a space-relevant radiation dose of 15 cGy that that can be utilized for future standardized ground studies on the nervous system.

O. Siu↗

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 NTRS2012

Radiation Shielding Materials Containing Hydrogen, Boron, and Nitrogen: Systematic Computational and Experimental Study

The key objectives of this study are to investigate, both computationally and experimentally, which forms, compositions, and layerings of hydrogen, boron, and nitrogen containing materials will offer the greatest shielding in the most structurally robust combination against galactic cosmic radiation (GCR), secondary neutrons, and solar energetic particles (SEP). The objectives and expected significance of this research are to develop a space radiation shielding materials system that has high efficacy for shielding radiation and that also has high strength for load bearing primary structures. Such a materials system does not yet exist. The boron nitride nanotube (BNNT) can theoretically be processed into structural BNNT and used for load bearing structures. Furthermore, the BNNT can be incorporated into high hydrogen polymers and the combination used as matrix reinforcement for structural composites. BNNT's molecular structure is attractive for hydrogen storage and hydrogenation. There are two methods or techniques for introducing hydrogen into BNNT: (1) hydrogen storage in BNNT, and (2) hydrogenation of BNNT (hydrogenated BNNT). In the hydrogen storage method, nanotubes are favored to store hydrogen over particles and sheets because they have much larger surface areas and higher hydrogen binding energy. The carbon nanotube (CNT) and BNNT have been studied as potentially outstanding hydrogen storage materials since 1997. Our study of hydrogen storage in BNNT - as a function of temperature, pressure, and hydrogen gas concentration - will be performed with a hydrogen storage chamber equipped with a hydrogen generator. The second method of introducing hydrogen into BNNT is hydrogenation of BNNT, where hydrogen is covalently bonded onto boron, nitrogen, or both. Hydrogenation of BN and BNNT has been studied theoretically. Hyper-hydrogenated BNNT has been theoretically predicted with hydrogen coverage up to 100% of the individual atoms. This is a higher hydrogen content than possible with hydrogen storage; however, a systematic experimental hydrogenation study has not been reported. A combination of the two approaches may be explored to provide yet higher hydrogen content. The hydrogen containing BNNT produced in our study will be characterized for hydrogen content and thermal stability in simulated space service environments. These new materials systems will be tested for their radiation shielding effectiveness against high energy protons and high energy heavy ions at the HIMAC facility in Japan, or a comparable facility. These high energy particles simulate exposure to SEP and GCR environments. They will also be tested in the LaRC Neutron Exposure Laboratory for their neutron shielding effectiveness, an attribute that determines their capability to shield against the secondary neutrons found inside structures and on lunar and planetary surfaces. The potential significance is to produce a radiation protection enabling technology for future exploration missions. Crew on deep space human exploration missions greater than approximately 90 days cannot remain below current crew Permissible Exposure Limits without shielding and/or biological countermeasures. The intent of this research is to bring the Agency closer to extending space missions beyond the 90-day limit, with 1 year as a long-term goal. We are advocating a systems solution with a structural materials component. Our intent is to develop the best materials system for that materials component. In this Phase I study, we have shown, computationally, that hydrogen containing BNNT is effective for shielding against GCR, SEP, and neutrons over a wide range of energies. This is why we are focusing on hydrogen containing BNNT as an innovative advanced concept. In our future work, we plan to demonstrate, experimentally, that hydrogen, boron, and nitrogen based materials can provide mechanically strong, thermally stable, structural materials with effective radiation shielding against GCR, SEP, and neutrons.

Radiation↗

NASA NTRSDate not supplied

Artificial Neural Networks to Predict Cognitive Impairment of Rodents Subjected to Space Radiation

INTRODUCTION We use artificial neural networks (ANNs) as an example machine learning (ML) tool to predict the cognitive performance impairment of rats induced by irradiation. The experimental data in the analyses is attentional set-shifting (ATSET) test scores from a rodent model exposed to ≤15 cGy of individual galactic cosmic radiation (GCR) ions: 4He, 28Si, or 56Fe, expected for a Lunar or Mars mission [1]. This work investigates rats at a subject-based level and uses applied dose and performance scores taken before irradiation to predict whether a rat will be impaired when irradiated. The results of this study are significant to crewed space missions as they support the potential of predicting an astronaut’s impairment in a specific task before spaceflight through the implementation of appropriately trained ML tools. METHODS Data used in this work are scores from the ATSET, a multi-stage constrained cognitive flexibility test [2]. Our computational model utilizes the number of attempts to reach the criterion to pass a stage as a behavioral performance measure for rats. We use the post-irradiation scores, generate thresholds from cumulative distribution plots of non-irradiated rats, and calculate the percent of irradiated rats whose scores fall below the threshold to infer how each radiation type/dose affects a population. Rats scoring above the threshold are labeled impaired while the others are non-impaired. We then employ ANNs as a typical ML technique, and use each subject’s individual scores taken before radiation along with the applied dose, to predict their personal susceptibility to cognitive impairment due to space radiation exposure. RESULTS AND CONCLUSION A significant finding is the exhibition of a dose-dependent increasing probability of impairment for 1 to 10 cGy of 28Si or 56Fe in the simple discrimination (SD) stage of the ATSET, and for 1 to 10 cGy of 56Fe in the compound discrimination (CD) stage. On a subject-based level, implementing ML classifiers such as ANNs identifies rats that have a higher tendency for impairment after GCR exposure [1]. The receiver operating characteristic (ROC) and the precision-recall (PR) curves of the ML models show a better prediction of impairment when 56Fe is the ion in question in both SD (Figure 1) and CD stages. They, however, do not depict impairment due to 4He in SD (Figure 1) and 28Si in CD, suggesting no dose-dependent impairment response in these cases. In this work, “good” prediction pertains to “better-than-random-chance”, due to the limited sample size and the high inter- and intra-individual variabilities in response to brain stimulation paradigms, as applicable to both animals and humans. More behavioral tests and biomarkers should be investigated on the same subjects, to be fed to the ML models to capture the agents responsible for performance alterations of some individuals versus others.

machine learning↗

NASA NTRSDate not supplied

Machine Learning Models to Predict Cognitive Impairment of Rodents Subjected to Space Radiation

INTRODUCTION We use artificial neural networks (ANNs) as an example machine learning (ML) tool to predict the cognitive performance impairment of rats induced by irradiation. The experimental data in the analyses is attentional set-shifting (ATSET) test scores from a rodent model exposed to ≤15 cGy of individual galactic cosmic radiation (GCR) ions: 4He, 28Si, or 56Fe, expected for a Lunar or Mars mission [1]. This work investigates rats at a subject-based level and uses applied dose and performance scores taken before irradiation to predict whether a rat will be impaired when irradiated. The results of this study are significant to crewed space missions as they support the potential of predicting an astronaut’s impairment in a specific task before spaceflight through the implementation of appropriately trained ML tools. METHODS Data used in this work are scores from the ATSET, a multi-stage constrained cognitive flexibility test [2]. Our computational model utilizes the number of attempts to reach the criterion to pass a stage as a behavioral performance measure for rats. We use the post-irradiation scores, generate thresholds from cumulative distribution plots of non-irradiated rats, and calculate the percent of irradiated rats whose scores fall below the threshold to infer how each radiation type/dose affects a population. Rats scoring above the threshold are labeled impaired while the others are non-impaired. We then employ ANNs as a typical ML technique, and use each subject’s individual scores taken before radiation along with the applied dose, to predict their personal susceptibility to cognitive impairment due to space radiation exposure. RESULTS AND CONCLUSION A significant finding is the exhibition of a dose-dependent increasing probability of impairment for 1 to 10 cGy of 28Si or 56Fe in the simple discrimination (SD) stage of the ATSET, and for 1 to 10 cGy of 56Fe in the compound discrimination (CD) stage. On a subject-based level, implementing ML classifiers such as ANNs identifies rats that have a higher tendency for impairment after GCR exposure [1]. The receiver operating characteristic (ROC) and the precision-recall (PR) curves of the ML models show a better prediction of impairment when 56Fe is the ion in question in both SD (Figure 1) and CD stages. They, however, do not depict impairment due to 4He in SD (Figure 1) and 28Si in CD, suggesting no dose-dependent impairment response in these cases. In this work, “good” prediction pertains to “better-than-random-chance”, due to the limited sample size and the high inter- and intra-individual variabilities in response to brain stimulation paradigms, as applicable to both animals and humans. More behavioral tests and biomarkers should be investigated on the same subjects, to be fed to the ML models to capture the agents responsible for performance alterations of some individuals versus others.

machine learning↗

NASA NTRS2007

Improvement of Risk Assessment from Space Radiation Exposure for Future Space Exploration Missions

Protecting astronauts from space radiation exposure is an important challenge for mission design and operations for future exploration-class and long-duration missions. Crew members are exposed to sporadic solar particle events (SPEs) as well as to the continuous galactic cosmic radiation (GCR). If sufficient protection is not provided the radiation risk to crew members from SPEs could be significant. To improve exposure risk estimates and radiation protection from SPEs, detailed variations of radiation shielding properties are required. A model using a modern CAD tool ProE (TM), which is the leading engineering design platform at NASA, has been developed for this purpose. For the calculation of radiation exposure at a specific site, the cosine distribution was implemented to replicate the omnidirectional characteristic of the 4 pi particle flux on a surface. Previously, estimates of doses to the blood forming organs (BFO) from SPEs have been made using an average body-shielding distribution for the bone marrow based on the computerized anatomical man model (CAM). The development of an 82-point body-shielding distribution at BFOs made it possible to estimate the mean and variance of SPE doses in the major active marrow regions. Using the detailed distribution of bone marrow sites and implementation of cosine distribution of particle flux is shown to provide improved estimates of acute and cancer risks from SPEs.

Kim, Myung-Hee Y.↗

NASA NTRS2018

Radiation and the Immune System

Radiation has profound effects on the immune system. This makes it particularly important to study in order to protect astronauts venturing into deep space and cancer patients considering radiotherapy treatments. Beyond the Earth's magentic field lies galactic cosmic radiation, which contains heavy ion based rays. Immune alterations in response to radiation depends on factors such as the type and amount of radiation, and potentially even the genes of the individual being exposed. In order to study the effects of cosmic radiation on the immune system, we are exposing primary human immune cells to various types and amounts of radiation. To measure sensitivity to radiation, we are quantifying the DNA damage within the cells before irradiation, 4 hours after irradiation, and 24 hours after irradiation. DNA damage is visualized by fluorescently staining for known DNA repair proteins, which get recruited to the site of damage within a cell. These results will be analyzed to search for correlations between immune cell responses and the type of radiation, amount of radiation, or any genetic markers present in the human blood donors. We will also be attempting to determine which specific immune cells are most suspectible to radiation damage. These correlations and discoveries will contribute to making long duration human deep space exploration a possibility, and can even be used to design more personalized and effective radiation treatments for cancer patients.

Malkani, Sherina S.↗

NASA NTRS2003

Measurement of Charged Particle Interactions in Spacecraft and Planetary Habitat Shielding Materials

Accurate models of health risks to astronauts on long-duration missions outside the geomagnetosphere will require a full understanding of the radiation environment inside a spacecraft or planetary habitat. This in turn requires detailed knowledge of the flux of incident particles and their propagation through matter, including the nuclear interactions of heavy ions that are a part of the Galactic Cosmic Radiation (GCR). The most important ions are likely to be iron, silicon, oxygen, and carbon. Transport of heavy ions through complex shielding materials including self-shielding of tissue modifies the radiation field at points of interest (e.g., at the blood-forming organs). The incident flux is changed by two types of interactions: (1) ionization energy loss, which results in reduced particle velocity and higher LET (Linear Energy Transfer); and (2) nuclear interactions that fragment the incident nuclei into less massive ions. Ionization energy loss is well understood, nuclear interactions less so. Thus studies of nuclear fragmentation at GCR-like energies are needed to fill the large gaps that currently exist in the database. These can be done at only a few accelerator facilities where appropriate beams are available. Here we report results from experiments performed at the Brookhaven National Laboratory s Alternating Gradient Synchrotron (AGS) and the Heavy Ion Medical Accelerator in Chiba, Japan (HIMAC). Recent efforts have focused on extracting charge-changing and fragment production cross sections from silicon beams at 400, 600, and 1200 MeV/nucleon. Some energy dependence is observed in the fragment production cross sections, and as in other data sets the production of fragments with even charge numbers is enhanced relative to those with odd charge numbers. These data are compared to the NASA-LaRC model NUCFRG2. The charge-changing cross section data are compared to recent calculations using an improved model due to Tripathi, which accurately predicts the observed (slight) energy dependence. An additional set of data will be presented from an analysis of shielding material performance in the 1 GeV/nucleon iron beam at the AGS. A wide variety of candidate materials for spacecraft construction, as well as elemental targets, have been placed in this beam and their effects on transmitted dose and dose equivalent measured. The results support a prediction by J. Wilson et al. that hydrogen-loaded materials give the greatest dose reduction per unit mass.

Zeitlin, Cary J.↗

NASA NTRSDate not supplied

NASA GeneLab Platform Utilized for Biological Response to Space Radiation in Animal Models

Ionizing radiation from Galactic Cosmic Rays (GCR) is one of the major risk factors that will impact the health of astronauts on extended missions outside the protective effects of Earth’s magnetic field. The NASA GeneLab project has detailed information on radiation exposure using animal models with curated dosimetry information for spaceflight experiments. We analyzed multiple GeneLab omics datasets associated with both ground-based and spaceflight radiation studies that included in vivo and in vitro approaches. A range of ions from protons to iron particles with doses from 0.1 Gy to 1.0 Gy for ground studies and samples flown in Low Earth Orbit (LEO) with total doses of 1.0 mGy to 30 mGy were utilized From this analysis we were able to identify distinct biological signatures associating specific ions with specific biological responses due to radiation exposure in space. For example, we discovered changes in mitochondrial function, ribosomal assembly, and immune pathways as a function of dose. We provided a summary of how the GeneLab’s rich database of omics experiments with animal models can be used to generate novel hypotheses to better understand human health risks from GCR exposures.

Afshin Beheshti↗

NASA NTRSDate not supplied

NASA GeneLab Platform Utilized for Space Radiation Dosimetry Biological Response Compared to Radiation Ground Studies

Ionizing radiation from Galactic Cosmic Rays (GCR) is one of the major risk factors that will impact the health of astronauts on extended missions outside the protective effects of Earth’s magnetic field. The NASA GeneLab project has detailed information on radiation exposure using animal models with curated dosimetry information for spaceflight experiments. We analyzed multiple GeneLab omics datasets associated with both ground-based and spaceflight radiation studies that included in vivo and in vitro approaches. A range of ions from protons to iron particles with doses from 0.1 Gy to 1.0 Gy for ground studies and samples flown in Low Earth Orbit (LEO) with total doses of 1.0 mGy to 30 mGy were utilized From this analysis we were able to identify distinct biological signatures associating specific ions with specific biological responses due to radiation exposure in space. For example, we discovered changes in mitochondrial function, ribosomal assembly, and immune pathways as a function of dose. We provided a summary of how the GeneLab’s rich database of omics experiments with animal models can be used to generate novel hypotheses to better understand human health risks from GCR exposures.

Afshin Beheshti↗

NASA NTRSDate not supplied

ExMC Ground-Based Space Radiation Analog Pilot Drug Stability Studay: Final Data Review

Uncertainty regarding space radiation effects on medication degradation and potency remains high, though early data suggest that space radiation may affect the potency and quality of some pharmaceuticals. In the absence of empirical spaceflight measurements to characterize this risk area for long-duration planetary missions, high-fidelity ground-based targeted radiation analogs could provide valuable insights. The NASA Human Research Program's (HRP) Exploration Medical Capability (ExMC) Element conducted a pilot study to characterize the chemical stability of four selected medications exposed to rapid switching, mixed-species simulated galactic cosmic radiation (GCR) beams at the NASA Space Radiation Laboratory (NSRL), at Brookhaven National Laboratory (BNL). The research objective was to compare the effects of simulated GCR beam exposures on drug stability to those previously observed following spaceflight.

Vernie R Daniels↗

NASA NTRSDate not supplied

Cardiovascular Responses to Simulated Spaceflight: Molecular Signatures and Surrogate Outputs to Measure CVD Risk

During extended space missions beyond low Earth orbit, astronauts will encounter prolonged periods of weightlessness and low dose space radiation. Previous studies have shown that exposure to small doses of high LET radiation (< 50 cGy) can lead to both short-term and long-term alterations in heart function, structure and underlying molecular mechanisms. In this study, we aim to identify the molecular signature associated with the cardiovascular response to simulated galactic cosmic radiation (5-ion GCR) alone or in combination with simulated weightlessness at time intervals relevant to mission length and recovery. Additionally, we aim to determine whether sex impacts cardiovascular responses to these spaceflight factors. Our overarching goal is to enhance our understanding of the cardiovascular risks associated with extended space missions and the clinical endpoints they suggest. We hypothesize that exposure to simulated space radiation leads to enduring alterations in the transcriptome, redox signaling and cytokine environment of cardiovascular tissue, some which have known links with reduced cardiovascular performance, aging, and increased risk of cardiovascular disease (CVD). Furthermore, we posit that simulated space radiation exposure in combination with simulated microgravity exacerbates cardiovascular deficits compared to single factor exposure. Female and male C57BL/6J mice, aged 23-24 weeks, were exposed to a single dose of 5, 15, or 50 cGy of 5-ion GCR, or sham-treated (0 cGy). Euthanasia was performed at 14 days and ~4 months post-irradiation. Hearts, aorta and blood plasma were collected shortly thereafter. RNA-sequencing of left ventricles at ~4 months post-GCR exposure revealed sex differences in the heart transcriptome with a few genes showing radiation-dependent changes in expression levels. Notably, some of the differentially expressed genes in 15 and 50 cGy GCR groups are known to play roles in the development of CVD. Analysis of protein levels of a subset of inflammatory cytokines in the heart indicated sex differences but no differences between sham and 50 cGy groups. Results also showed correlations among differentially expressed genes and a subset of inflammatory cytokines, with some correlations altered by GCR exposure. These findings suggest that GCR exposure can modify protein and gene networks linked to inflammation and CVD progression. In the aorta, telomere lengths were comparable across treatment groups sexes. Mitochondrial copy number is a biomarker for mitochondrial function with decreased copy numbers associated with cardiometabolic disease traits. Mitochondrial copy numbers of aorta also showed no sex nor dose differences. In a second study, mice underwent one week of simulated microgravity by hindlimb unloading (HU) and then exposed to a single dose of 15 cGy of 5-ion GCR. HU was conducted for an additional two weeks following GCR exposure. Single factor exposure groups (HU or GCR only) also were included in the study. Euthanasia was then performed and the same tissues were collected. Protein levels of select inflammatory cytokines in the heart showed sex-dependent differences in expression. In the aorta, telomere lengths and mitochondrial copy number also showed sex differences. In summary, our results indicate differences between sexes in biomarkers related to cardiovascular health. Exposure to 5-ion GCR or HU, alone or in combination, did not result in changes in most of the cardiovascular biomarkers that were examined. However, in the heart, simulated space radiation at doses of 15 and 50 cGy led to long-term alterations in the expression levels of a small group of genes known to be associated with the progression of CVD. The long-term transcriptomic changes resulting from exposure to simulated space radiation should be carefully investigated to mitigate adverse cardiovascular events during and after deep space missions. Our results also highlight the importance of sex-specific strategies in monitoring and maintaining cardiovascular health during and after deep space missions.

cardiovascular↗

NASA NTRSDate not supplied

Neurovascular Responses to Simulated Deep Space Radiation in a Human Organ-on-a-Chip Model

A major health risk for human deep space exploration is central nervous system (CNS) damage by galactic cosmic ray radiation. Simulated galactic cosmic rays or their components, especially the high-linear energy transfer (LET) particles such as 56Fe ions, have been shown to cause CNS damage, neuroinflammation and cognitive dysfunction in rodent models, but their effects on human CNS remain to be investigated. CNS damage from any insult, including ionizing radiation, is partially mediated by the blood-brain barrier (BBB), which regulates interactions between CNS and the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuroinflammation. However, there have been few studies on BBB and astrocyte functions in regulating CNS responses, especially in human tissue analogs. Therefore, we utilized a high-throughput 3D organ-on-a-chip system, seeded with human induced pluripotent stem cell-derived astrocytes and brain endothelial cells, or brain endothelial cells alone, to study human neurovascular responses to simulated deep space radiation. We investigated the permeability and morphology of vascular structures formed by endothelial cells, as well as oxidative stress and secreted cytokines and chemokine levels over 1-7 days after irradiation with 0.25 – 0.5 Gy 5-ion simplified simulated galactic cosmic rays or 0.3 – 0.8 Gy high-LET 600 MeV/n 56Fe particles, and compared the outcomes to low-LET X-ray irradiation. We observed that simulated deep space radiation caused delayed astrocyte activation in a pattern resembling CNS responses to brain injury, caused oxidative stress and the production of inflammatory cytokines, and compromised BBB integrity by damaging tight junctions, thus increasing vascular permeability. Furthermore, our results indicate that astrocytes have a dual role in regulating radiation responses: they exacerbate blood-brain barrier permeability early after irradiation, followed by switching to a more protective scar-like phenotype by reducing oxidative stress and pro-inflammatory cytokine and chemokine secretion. In a follow-up study using the same platform, we investigated the dose-rate effects of ionizing radiation, by exposing our model to chronic, low dose-rate, gamma radiation. Our model was significantly improved by adding additional cell types composing the BBB, modelling immune cell infiltration into the brain, and studying the effect of an antioxidant, to measure more complex outcomes and model more closely the effect of deep space radiation on the human BBB. In summary, our results present a human neurovascular model for space radiation studies and potential future automated payload adaptation, and suggest astrocyte regulatory mechanisms as targets for countermeasures to mitigate human neurovascular impairments during deep space exploration.

Ionizing radiation↗