NASA Space Radiation Laboratory Research Articles

Operation experience of LION and RHIC-EBIS for RHIC and NSRL

LION is a laser ablation ion source to provide singly charged heavy ions of various species for RHIC-EBIS. High charge state heavy ion beams from RHIC-EBIS are used for RHIC physics experiments and NASA Space Radiation Laboratory (NSRL) quasi-simultaneously. The demands for heavy ion beams are growing and more ion species are available and more NSRL beam time is used because of unique capability and flexibility of the sources. With the combination of LION and RHIC-EBIS, ion species can be switched on a pulse-by-pulse basis without the effect of previously used species. The present performance and operation experiences of LION and RHIC-EBIS are shown.

Late onset cardiovascular dysfunction in adult mice resulting from galactic cosmic ray exposure

SummaryThe complex and inaccessible space radiation environment poses an unresolved risk to astronaut cardiovascular health during long-term space exploration missions. To model this risk, healthy male c57BL/6 mice aged six months (corresponding to an astronaut of 34 years) were exposed to simplified galactic cosmic ray (GCR5-ion; 5-ion sim) irradiation at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratories (BNL). Multi-modal cardiovascular functional assessments performed longitudinally and terminally revealed significant impairment in cardiac function in mice exposed to GCR5-ion compared to unirradiated controls, gamma irradiation, or single mono-energetic ions (56Fe or 16O). GCR5-ion-treated mice exhibited increased arterial elastance likely mediated by disruption of elastin fibers. This study suggests that a single exposure to GCR5-ion is associated with deterioration in cardiac structure and function that becomes apparent long after exposure, likely associated with increased morbidity and mortality. These findings represent important health considerations when preparing for successful space exploration.

Response of Arabidopsis thaliana and Mizuna Mustard Seeds to Simulated Space Radiation Exposures.

One of the major concerns for long-term exploration missions beyond the Earth’s magnetosphere is consequences from exposures to solar particle event (SPE) protons and galactic cosmic rays (GCR). For long-term crewed Lunar and Mars explorations, the production of fresh food in space will provide both nutritional supplements and psychological benefits to the astronauts. However, the effects of space radiation on plants and plant propagules have not been sufficiently investigated and characterized. In this study, we evaluated the effect of two different compositions of charged particles-simulated GCR, and simulated SPE protons on dry and hydrated seeds of the model plant Arabidopsis thaliana and the crop plant Mizuna mustard [Brassica rapa var. japonica]. Exposures to charged particles, simulated GCRs (up to 80 cGy) or SPEs (up to 200 cGy), were performed either acutely or at a low dose rate using the NASA Space Radiation Laboratory (NSRL) facility at Brookhaven National Lab (BNL). Control and irradiated seeds were planted in a solid phytogel and grown in a controlled environment. Five to seven days after planting, morphological parameters were measured to evaluate radiation-induced damage in the seedlings. After exposure to single types of charged particles, as well as to simulated GCR, the hydrated Arabidopsis seeds showed dose- and quality-dependent responses, with heavier ions causing more severe defects. Seeds exposed to simulated GCR (dry seeds) and SPE (hydrated seeds) had significant, although much less damage than seeds exposed to heavier and higher linear energy transfer (LET) particles. In general, the extent of damage depends on the seed type.

Shelf Life and Simulated Gastrointestinal Tract Survival of Selected Commercial Probiotics During a Simulated Round-Trip Journey to Mars.

To enhance the gastrointestinal health of astronauts, probiotic microorganisms are being considered for inclusion on long-duration human missions to the Moon and Mars. Here we tested three commercial probiotics—Bifidobacterium longum strain BB536, Lactobacillus acidophilus strain DDS-1, and spores of Bacillus subtilis strain HU58—for their survival to some of the conditions expected to be encountered during a 3-year, round trip voyage to Mars. All probiotics were supplied as freeze-dried cells in capsules at a titer of >109 colony forming units per capsule. Parameters tested were survival to: (i) long-term storage at ambient conditions, (ii) simulated Galactic Cosmic Radiation and Solar Particle Event radiation provided by the NASA Space Radiation Laboratory, (iii) exposure to simulated gastric fluid, and (iv) exposure to simulated intestinal fluid. We found that radiation exposure produced minimal effects on the probiotic strains. However, we found that that the shelf-lives of the three strains, and their survival during passage through simulations of the upper GI tract, differed dramatically. We observed that only spores of B. subtilis were capable of surviving all conditions and maintaining a titer of >109 spores per capsule. The results indicate that probiotics consisting of bacterial spores could be a viable option for long-duration human space travel.

Impact of galactic cosmic ray simulation on nutritional content of foods

Foods packaged for future deep-space exploration missions may be prepositioned ahead of astronaut arrival and will be exposed to galactic cosmic rays (GCRs) and solar radiation in deep space at higher levels and different spectrums than those found in low-Earth orbit (LEO). In this study, we have evaluated the impact of a GCR simulation (approximately 0.5 and 5 Gy doses) at the NASA Space Radiation Laboratory (NSRL) on two retort thermostabilized food products that are good sources of radiation labile nutrients (thiamin, vitamin E, or unsaturated fats). No trends or nutritional differences were found between the radiation-treated samples and the control immediately after treatment or one-year after treatment. Small changes in a few nutrients were measured following one-year of storage. Further studies may be needed to confirm these results, as the foods in this study were heterogeneous, and this may have masked meaningful changes due to pouch-to-pouch variations.

Beamline and Flight Comparisons of the ARMAS Flight Module With the Tissue Equivalent Proportional Counter for Improving Atmospheric Radiation Monitoring Accuracy

AbstractIonizing radiation at aircraft and commercial suborbital spaceflight altitudes is driven by space weather and is a health concern for crew and passengers. We compare the response functions of two radiation detectors that were exposed to four different ground‐based laboratory radiation fields as well as flown alongside each other on aircraft. The detectors were a tissue equivalent proportional counter (TEPC) and a Teledyne silicon micro dosimeter chip that was integrated into an Automated Radiation Measurements for Aerospace Safety Flight Module (ARMAS FM). Both detectors were flown onboard commercial and research aircraft. In addition, both detectors were exposed neutrons at the Los Alamos Neutron Science Center, protons at Loma Linda University Medical Center, 56Fe particles at the NASA Space Radiation Laboratory, and also a gamma radiation source at Lawrence Livermore National Laboratory. The response of each of these instruments as well as derived dosimetric quantities are compared for each radiation exposure and the ratio for converting ARMAS absorbed dose in silicon to an estimated absorbed dose in tissue is obtained. This process resulted in the first definitive calibration of the silicon‐based detector like ARMAS to TEPC. In particular, with seven flights of both instruments together, the ARMAS‐derived dose in tissue was then validated with the TEPC‐measured dose in tissue and these results are reported. This work provides a method for significantly improving the accuracy of radiation measurements relevant to human tissue safety using a silicon detector that is easy to deploy and can report data in real time.

Beam characterization at NSRL for radiobiological experiments—phase 1

An experimental campaign was carried out at the NASA Space Radiation Laboratory to perform an additional, independent dosimetric characterization of the beams of protons, helium and carbon ions for radiobiological experiments. The campaign was undertaken by the request and with the support from the National Cancer Institute, U.S. In this initial phase, the goals were to obtain a first assessment of the dosimetric reproducibility of the beam control system, including analysis of spatial homogeneity and evaluation of ion beam contamination. They should facilitate the design of further experimental campaigns for beam characterization for radiobiological experiments. Measurements included reference dosimetry with comparison of in-house and external ionization chambers and electrometers, lateral-dose profile measurements in air, depth-dose profile in a water tank, evaluation of water equivalent thickness of a HDPE binary range shifter and estimation of impurities of the investigated helium-ion beam. The experiments and results are presented.

Determination of Chromosome Aberrations in Human Fibroblasts Irradiated by Mixed Fields Generated with Shielding.

To better study biological effects of space radiation using ground-based facilities, the NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory has been upgraded to rapidly switch ions and energies. This has allowed investigators to design irradiation protocols comprising a mixture of ions and energies more indicative of the galactic cosmic ray (GCR) environment. Despite these advancements, beam selection and delivery schemes should be optimized against facility and experimental constraints and validated to ensure such irradiations are a suitable representation of the space environment. Importantly, since experiments are time consuming and expensive, models capable of predicting biological outcomes over a range of irradiation conditions (single ion, sequential multi ion or mixed fields) are needed to support such efforts. In this work, human fibroblasts were placed behind 20 g/cm2 aluminum and 10.345 g/cm2 polyethylene and irradiated separately by 344 MeV hydrogen, 344 MeV/n helium, 450 MeV/n oxygen and 950 MeV/n iron ions at various doses. The fluorescence in situ hybridization (FISH) whole chromosome painting technique was then used to assess the cells for chromosome aberrations (CAs), notably simple exchanges. A multi-scale modeling approach was also developed to predict the formation of chromosome aberrations in these experiments. The Geant4 simulation toolkit was used to determine the spectra of particles and energies produced by interactions between the incident beams and shielding. The simulated mixed field generated by shielding was then transferred into the track structure code, RITRACKS (relativistic ion tracks), to generate three-dimensional (3D) voxelized dose maps at the nanometer scale. Finally, these voxel dose maps were input into the new damage and repair model, RITCARD (radiation-induced tracks, chromosome aberrations, repair and damage), to predict the formation of various CAs. The multi-scale model described herein is a significant advancement for the computational tools used to predict biological outcomes in cells exposed to highly complex, mixed ion fields related to the GCR environment. Results show that the simulation and experimental data are in good agreement for the complex radiation fields generated by all ions incident on shielding for most data points. The differences between model predictions and measurements are discussed. Although improvements are needed, the model extends current capabilities for evaluating beam selection and delivery schemes at the NSRL ground-based GCR simulator and for informing NASA risk projection models in the future.

NASA's first ground-based Galactic Cosmic Ray Simulator: Enabling a new era in space radiobiology research.

With exciting new NASA 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 radiation (GCR) and the possibility of a large solar particle event (SPE). Gateway, lunar landers, and surface habitats will be designed to protect crew against SPEs 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 carcinogenesis, central nervous system (CNS) effects resulting in potential in-mission cognitive or behavioral impairment and/or late neurological disorders, degenerative tissue effects including 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. Historically, most research on understanding space radiation-induced health risks has been performed using acute exposures of monoenergetic single-ion beams. However, the space radiation environment consists of a wide variety of ion species over a broad energy range. Using the fast beam switching and controls systems technology recently developed at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory, a new era in radiobiological research is possible. NASA has developed the “GCR Simulator” 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 (approximately 65%–75%) and helium ions (approximately 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 5 heavy ions of C, O, Si, Ti, and Fe. A polyethylene degrader system 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 approximately 75 minutes. To more closely simulate the low-dose rates found in space, sequential field exposures can be divided into daily fractions over 2 to 6 weeks, with individual beam fractions as low as 0.1 to 0.2 mGy. In the large beam configuration (60 × 60 cm2), 54 special housing cages can accommodate 2 to 3 mice each for an approximately 75 min duration or 15 individually housed rats. On June 15, 2018, the NSRL made a significant achievement by completing the first operational run using the new GCR simulator. This paper discusses NASA’s innovative technology solution for a ground-based GCR simulator at the NSRL to accelerate our understanding and mitigation of health risks faced by astronauts. Ultimately, the GCR simulator will require validation across multiple radiogenic risks, endpoints, doses, and dose rates.

Simulating galactic cosmic ray effects: Synergy modeling of murine tumor prevalence after exposure to two one-ion beams in rapid sequence

Health risks from galactic cosmic rays (GCR) in space travel above low earth orbit remain a concern. For many years accelerator experiments investigating space radiation induced prevalence of murine Harderian gland (HG) tumorigenesis have been performed to help estimate GCR risks. Most studies used acute, relatively low fluence, exposures. Results on a broad spectrum of individual ions and linear energy transfers (LETs) have become available. However, in space, the crew are exposed simultaneously to many different GCR. Recent upgrades at the Brookhaven NASA Space Radiation Laboratory (NSRL) now allow mixtures in the form of different one-ion beams delivered in rapid sequence. This paper uses the results of three two-ion mixture experiments to illustrate conceptual, mathematical, computational, and statistical aspects of synergy analyses and also acts as an interim report on the mixture experiments' results. The results were interpreted using the following: (a) accumulated data from HG one-ion accelerator experiments; (b) incremental effect additivity synergy theory rather than simple effect additivity synergy theory; (c) parsimonious models for one-ion dose-effect relations; and (d), computer-implemented numerical methods encapsulated in freely available open source customized software. The main conclusions are the following. As yet, the murine HG tumorigenesis experimental studies show synergy in only one case out of three. Moreover, some theoretical arguments suggest GCR-simulating mixed beams are not likely to be synergistic. However, more studies relevant to possible synergy are needed by various groups that are studying various endpoints. Especially important is the possibility of synergy among high-LET radiations, since individual high-LET ions have large relative biological effectiveness for many endpoints.Selected terminology, symbols, and abbreviations. DER – dose-effect relation; E(d) – DER of a one-ion beam, where d is dose; HG prevalence p – in this paper, p is the number of mice with at least one Harderian gland tumor divided by the number of mice that are at risk of developing Harderian gland tumors (so that in this paper prevalence p can never, conceptually speaking, be greater than 1); IEA – incremental effect additivity synergy theory; synergy level – a specification, exemplified in Fig. 5, of how clear-cut an observed synergy is; mixmix principle – a consistency condition on a synergy theory which insures that the synergy theory treats mixtures of agent mixtures in a mathematically self-consistent way; NTE – non-targeted effect(s); NSNA – neither synergy nor antagonism; SEA – simple effect additivity synergy theory; TE – targeted effect(s); β* – ion speed relative to the speed of light, with 0 < β* < 1; SLI – swift light ion(s).

Cluster ion source for external injection and high capacity filling of light elements into the relativistic heavy ion collider electron beam ion source.

An advanced Electron Beam Ion Source (EBIS) is the primary ion source to supply highly charged ion beams of different elements to the Relativistic Heavy Ion Collider (RHIC) and to the NASA Space Radiation Laboratory (NSRL). Intense beams of highly charged ions of various elements of the periodic table, ranging from helium to uranium, have been demonstrated since EBIS became operational in 2010. EBIS routinely provides ion beams to RHIC and NSRL quasisimultaneously with about 1 s switching time between different ion species. Such unique flexibility and rapid switching between ion species are based on external injection of singly charged ions into the EBIS trap either in "fast" or "slow" injection modes. At present, a Laser Ion Source (LIS) provides most of the ion species of solid materials using the "fast" injection mode into the EBIS trap and a Hollow Cathode Ion Source (HCIS) provides most of the ion species of gaseous elements using the "slow" injection mode into the EBIS trap. Gas injection into the EBIS trap is also possible and has been used but imposes some restrictions for the simultaneous generation of highly charged ions such as Au32+ ions for RHIC and ions of gaseous species for NSRL. Because light ions have relatively high velocity inside the EBIS trap, efficient injection of hydrogen and helium ions and filling of the EBIS trap to high capacity is difficult from either LIS or HCIS. To overcome this restriction and enhance EBIS operational capability, we suggest injecting beams of hydrogen and helium cluster ions into the EBIS trap. Required parameters of cluster ion beam injection into the EBIS trap are estimated, and advantages of such an injection are highlighted. A cluster ion source with required high intensity is visible and will be designed, built, optimized, and tested.

Lung cancer progression using fast switching multiple ion beam radiation and countermeasure prevention

Most of the research in understanding space radiation-induced cancer progression and risk assessment has been performed using mono-energetic single-ion beams. However, the space radiation environment consists of a wide variety of ion species with a various range of energies. Using the fast beam switching technology developed at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), ion species can be switched rapidly allowing investigators to use multiple ions with different energies to simulate more closely the radiation environment found in space. Here, we exposed a lung cancer susceptible mouse model (K-rasLA-1) to three sequential ion beams: Proton (H) (120 MeV/n) 20 cGy, Helium (He) (250 MeV/n) 5.0 cGy, and Silicon (Si) (300 MeV/n) 5.0 cGy with a dose rate of 0.5 cGy/min. Using three ion beams we performed whole body irradiation with a total dose of 30 cGy in two different orders: 3B-1 (H→He→Si) and 3B-2 (Si→He→H) and used 30 cGy H single-ion beam as a reference. In this study we show that whole-body irradiation with H→He→Si increases the incidence of premalignant lesions and systemic oxidative stress in mice 100 days post-irradiation more than (Si→He→H) and H only irradiation. Additionally, we observed an increase in adenomas with atypia and adenocarcinomas in H→He→Si irradiated mice but not in (Si→He→H) or H (30 cGy) only irradiated mice. When we used the H→He→Si irradiation sequence but skipped a day before exposing the mice to Si, we did not observe the increased incidence of cancer initiation and progression. We also found that a non-toxic anti-inflammatory, anti-oxidative radioprotector (CDDO-EA) reduced H→He→Si induced oxidative stress and cancer initiation almost back to baseline. Thus, exposure to H→He→Si elicits significant changes in lung cancer initiation that can be mitigated using CDDO-EA.

Abstract 3729: Heavy-ion space radiation exposure is a potential risk factor for gastrointestinal tumorigenesis even at extremely low doses

Abstract Heavy-ion radiation (HZE)-induced carcinogenesis is a major concern in astronauts planning to undertake long-term deep space exploration, such as a mission to the Mars. Due to high-LET (linear energy transfer) characteristics of HZE ions present in deep space environment, the Mars mission is expected to substantially enhance gastrointestinal cancer risk in astronauts, relative to low-LET radiation. Previously, using three different mouse models of human colorectal cancer (APCmin/+, APC1638N/+ and IL10-/- mouse) we have unequivocally demonstrated a significantly higher risk of intestinal and colonic tumorigenesis after exposure to energetic heavy ions. This study aims to obtain quantitative GI-tumorigenesis data at space relevant doses (5-50 cGy) of heavy ions covering a broad-spectrum of linear energy transfer (2-148 keV/μm), relative to γ-radiation. The APC1638N/+ mouse was used due to its best signal-to-noise ratio among all previously studied mouse models of human gastrointestinal cancer. Both female and male APC1638N/+ mice (6-8 weeks, n=20) were whole-body exposed to sham-radiation, γ-rays, 4He (2 keV/μm), 12C (13 keV/μm), 16O (22 keV/μm), 28Si (69 keV/μm), and 56Fe (148 keV/μm) -ion radiation at 5, 10, and 50 cGy dose at the NASA Space Radiation Laboratory (NSRL) in Brookhaven National Laboratory. Mice were euthanized at 150 d after radiation exposure and intestinal and colon tumor frequency and size were scored and analyzed as a function of dose, LET, and gender. The highest increase in tumor frequency was observed after 28Si followed by 56Fe, 16O, 12C, and 4He radiation, and male preponderance for tumorigenesis was evident for each radiation type and dose. At 50 cGy dose, no significant difference in tumorigenesis was observed between γ and 4He. However, at lower doses (5 and 10 cGy) significantly higher tumorigenesis was noted after 4He exposure. Furthermore, calculation of relative biological effectiveness (RBE) for tumorigenesis showed the highest value with 28Si and lower doses showed greater RBE relative to higher doses. No statistical difference in tumorigenesis pattern was evident between 16O and 12C at all studied doses. In addition no significant change in tumorigenesis pattern was evident between 28Si and 56Fe in female mice. Analysis showed greater tumorigenesis per unit of radiation (per cGy) at lower doses suggesting radiation-induced tumorigenesis reaching a saturation point at higher doses. The lack of understanding on radiation quality effects is one of the major uncertainties in space radiation exposure-associated cancer risk prediction. Using a broad-spectrum of HZE-ions we have demonstrated the dependence of gastrointestinal tumorigenesis on radiation quality even at very low doses, which has implications in cancer risk prediction for astronauts and also for accessing secondary cancer risks after particle radiotherapy. Citation Format: Shubhankar Suman, Santosh Kumar, Bo-Hyun Moon, Jerry Angdisen, Bhaskar VS Kallakury, Albert J. Fornace, Kamal Datta. Heavy-ion space radiation exposure is a potential risk factor for gastrointestinal tumorigenesis even at extremely low doses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3729.

Abstract 3736: Space radiation-induced decline in gut autophagy and expansion of both mitotic and senescent population denotes an aging phenotype with enhanced cancer risk

Abstract Exposure to space radiation is known to alter a myriad of cellular processes that could potentially affect astronauts’ health during and after long duration’s space missions. Due to high-LET (linear energy transfer) characteristics of energetic heavy ions (HZE) present in space, astronauts are predicted to be at higher risk for gastrointestinal cancer development. Proliferative epithelial cells in gastrointestinal (GI) tissue are highly radiosensitive and in our previous studies we have demonstrated a persistent stress phenotype in crypt cells after heavy ion space radiation exposure. However, uncertainty remains in our understanding of how heavy ions induce chronic stress and inflammation is linked to higher cancer risk. The purpose of the current study was to assess late effects of heavy ion (56-Fe) on the autophagy process that is required to recycle damaged cellular components and its role in HZE-induced gastrointestinal carcinogenesis. C57BL6/J mice were exposed to 1.6 Gy of 56-Fe radiation at NASA Space Radiation Laboratory (NSRL). Mice were euthanized 2-month after radiation and intestinal tissues were analyzed for oxidative stress and associated DNA damage, and alterations in antioxidant response and autophagy signaling. Further, cells underdoing mitosis, autophagy and stress-induced senescence were also scored and alterations in cell signaling pathways with established role in carcinogenesis were evaluated. Energetic heavy ions exposure resulted in a long-term increase in intracellular reactive oxygen species (ROS), accompanied with decreased expression of key antioxidant genes (Gpx, SOD and catalase). Increase in both mitochondrial and cytosolic ROS was evident as both loss of mitochondrial membrane potential (MMP) and increase in prooxidant Nox1 expression was found. Paradoxical increases in phospho-histone-3 positive (mitotic) and p16 positive (senescent) cells were found, however decreases in autophagy positive (LC3B) cells was noted in HZE-exposed mouse intestine. Upregulation of upstream mTOR-PI3K-AKT signaling and p62 were noticed in long-term suppression of autophagy (Atg12, LC3B and Beclin-1) after HZE-exposure. Here, we show that space radiation downregulated autophagy processes, which are an important cellular mechanism involved in suppression of carcinogenesis. When considered along with upregulation of proliferative pathways and increased oxidative stress, our data suggest increased risk of chronic GI diseases including cancer due to late persistence of damaged organelles in cells after energetic heavy ion radiation exposures. Collectively, this study demonstrates a unique phenomenon of heavy ion-induced suppression of autophagy concurrent with increases in both mitotic and senescent cells indicating a premature aging phenotype with enhanced cancer risk. Citation Format: Kamal Datta, Shubhankar Suman, Bo-Hyun Moon, Albert J. Fornace. Space radiation-induced decline in gut autophagy and expansion of both mitotic and senescent population denotes an aging phenotype with enhanced cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3736.

Late Effects of 16O-Particle Radiation on Female Social and Cognitive Behavior and Hippocampal Physiology

The radiation environment in space remains a major concern for manned space exploration, as there is currently no shielding material capable of fully protecting flight crews. Additionally, there is growing concern for the social and cognitive welfare of astronauts, due to prolonged radiation exposure and confinement they will experience on a mission to Mars. In this artice, we report on the late effects of 16O-particle radiation on social and cognitive behavior and neuronal morphology in the hippocampus of adult female mice. Six-month-old mice received 16O-particle whole-body irradiation at doses of either 0.25 or 0.1 Gy (600 MeV/n; 18-33 cGy/min) at the NASA's Space Radiation Laboratory in Upton, NY. At nine months postirradiation, the animals underwent behavioral testing in the three-chamber sociability, novel object recognition and Y-maze paradigms. Exposure to 0.1 or 0.25 Gy 16O significantly impaired object memory, a 0.25 Gy dose impaired social novelty learning, but neither dosage impaired short-term spatial memory. We observed significant decreases in mushroom spine density and dendrite morphology in the dentate gyrus, cornu ammonis 3, 2 and 1 of the hippocampus, which are critical areas for object novelty and sociability processing. Our data suggest exposure to 16O modulates hippocampal pyramidal and granular neurons and induces behavioral deficits at a time point of nine months after exposure in females.

∆E/∆E Measurements of Energetic Ions Using CVD Diamond Detectors

Experimental and computational results of a ΔE/ΔE diamond detection system are presented. The ΔE/ΔE detection system was evaluated using energetic proton and iron beams striking thick polyethylene targets at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL). The measured data for diamond sensor A show good agreement with the Geant4 simulation. In addition, simulations have demonstrated the ability to identify hydrogen isotopes using a diamond detection system.

Late effects of 1H irradiation on hippocampal physiology

NASA’s Missions to Mars and beyond will expose flight crews to potentially dangerous levels of charged-particle radiation. Of all charged nuclei, 1H is the most abundant charged particle in both the galactic cosmic ray (GCR) and solar particle event (SPE) spectra. There are currently no functional spacecraft shielding materials that are able to mitigate the charged-particle radiation encountered in space. Recent studies have demonstrated cognitive injuries due to high-dose 1H exposures in rodents. Our study investigated the effects of 1H irradiation on neuronal morphology in the hippocampus of adult male mice. 6-month-old mice received whole-body exposure to 1H at 0.5 and 1 Gy (150 MeV/n; 0.35–0.55 Gy/min) at NASA's Space Radiation Laboratory in Upton, NY. At 9-months post-irradiation, we tested each animal's open-field exploratory performance. After sacrifice, we dissected the brains along the midsagittal plane, and then either fixed or dissected further and snap-froze them. Our data showed that exposure to 0.5 Gy or 1 Gy 1H significantly increased animals’ anxiety behavior in open-field testing. Our micromorphometric analyses revealed significant decreases in mushroom spine density and dendrite morphology in the Dentate Gyrus, Cornu Ammonis 3 and 1 of the hippocampus, and lowered expression of synaptic markers. Our data suggest 1H radiation significantly increased exploration anxiety and modulated the dendritic spine and dendrite morphology of hippocampal neurons at a dose of 0.5 or 1 Gy.

Age as a factor in the responsiveness of the organism to the disruption of cognitive performance by exposure to HZE particles differing in linear energy transfer

Exposure to particles of high energy and charge (HZE particles) can produce decrements in cognitive performance. A series of experiments exposing rats to different HZE particles was run to evaluate whether the performance decrement was dependent on the age of the subject at the time of irradiation. Fischer 344 rats that were 2-, 11- and 15/16-months of age were exposed to 16O, 48Ti, or 4He particles at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. As previously observed following exposure to 56Fe particles, exposure to the higher LET 48Ti particles produced a disruption of cognitive performance at a lower dose in the older subjects compared to the dose needed to disrupt performance in the younger subjects. There were no age related changes in the dose needed to produce a disruption of cognitive performance following exposure to lower LET 16O or 4He particles. The threshold for the rats exposed to either 16O or 4He particles was similar at all ages. Because the 11- and 15-month old rats are more representative of the age of astronauts (45–55 years old) the present results indicate that particle LET may be a critical factor in estimating the risk of developing a cognitive deficit following exposure to space radiation on exploratory class missions.

Effects of 1H + 16O Charged Particle Irradiation on Short-Term Memory and Hippocampal Physiology in a Murine Model.

Radiation from galactic cosmic rays (GCR) poses a significant health risk for deep-space flight crews. GCR are unique in their extremely high-energy particles. With current spacecraft shielding technology, some of the predominant particles astronauts would be exposed to are 1H + 16O. Radiation has been shown to cause cognitive deficits in mice. The hippocampus plays a key role in memory and cognitive tasks; it receives information from the cortex, undergoes dendritic-dependent processing and then relays information back to the cortex. In this study, we investigated the effects of combined 1H + 16O irradiation on cognition and dendritic structures in the hippocampus of adult male mice three months postirradiation. Six-month-old male C57BL/6 mice were irradiated first with 1H (0.5 Gy, 150 MeV/n) and 1 h later with 16O (0.1 Gy, 600 MeV/n) at the NASA Space Radiation Laboratory (Upton, NY). Three months after irradiation, animals were tested for hippocampus-dependent cognitive performance using the Y-maze. Upon sacrifice, molecular and morphological assessments were performed on hippocampal tissues. During Y-maze testing, the irradiated mice failed to distinguish the novel arm, spending approximately the same amount of time in all three arms during the retention trial relative to sham-treated controls. Irradiated animals also showed changes in expression of glutamate receptor subunits and synaptic density-associated proteins. 1H + 16O radiation compromised dendritic morphology in the cornu ammonis 1 and dentate gyrus within the hippocampus. These data indicate cognitive injuries due to 1H + 16O at three months postirradiation.

High LET Carbon Ion Radiation Therapy in the Treatment of a Primary Mouse Sarcoma Model at the NASA Space Radiation Laboratory

High LET Carbon Ion Radiation Therapy in the Treatment of a Primary Mouse Sarcoma Model at the NASA Space Radiation Laboratory