NASA Space Radiation Laboratory Research Articles

Low and high dose rate heavy ion radiation-induced intestinal and colonic tumorigenesis in APC1638N/+ mice

Ionizing radiation (IR) is a recognized risk factor for colorectal cancer (CRC) and astronauts undertaking long duration space missions are expected to receive IR doses in excess of permissible limits with implications for colorectal carcinogenesis. Exposure to IR in outer space occurs at low doses and dose rates, and energetic heavy ions due to their high linear energy transfer (high-LET) characteristics remain a major concern for CRC risk in astronauts. Previously, we have demonstrated that intestinal tumorigenesis in a mouse model (APC1638N/+) of human colorectal cancer was significantly higher after exposure to high dose rate energetic heavy ions relative to low-LET γ radiation. The purpose of the current study was to compare intestinal tumorigenesis in APC1638N/+ mice after exposure to energetic heavy ions at high (50cGy/min) and relatively low (0.33cGy/min) dose rate. Male and female mice (6–8 weeks old) were exposed to either 10 or 50cGy of 28Si (energy: 300MeV/n; LET: 70keV/μm) or 56Fe (energy: 1000MeV/n; LET: 148keV/μm) ions at NASA Space Radiation Laboratory in Brookhaven National Laboratory. Mice (n=20 mice/group) were euthanized and intestinal and colon tumor frequency and size were counted 150days after radiation exposure. Intestinal tumorigenesis in male mice exposed to 56Fe was similar for high and low dose rate exposures. Although male mice showed a decreasing trend at low dose rate relative to high dose rate exposures, the differences in tumor frequency between the two types of exposures were not statistically significant after 28Si radiation. In female mice, intestinal tumor frequency was similar for both radiation type and dose rates tested. In both male and female mice intestinal tumor size was not different after high and low dose rate radiation exposures. Colon tumor frequency in male and female mice after high and low dose rate energetic heavy ions was also not significantly different. In conclusion, intestinal and colonic tumor frequency and size was similar irrespective of energetic heavy ion radiation dose rate suggesting that carcinogenic potential of energetic heavy ions is independent of dose rate.

Overview of the NASA space radiation laboratory

The NASA Space Radiation Laboratory (NSRL) is a multidisciplinary center for space radiation research funded by NASA and located at the Brookhaven National Laboratory (BNL), Upton NY. Operational since 2003, the scope of NSRL is to provide ion beams in support of the NASA Humans in Space program in radiobiology, physics and engineering to measure the risk and ameliorate the effect of radiation in space. Recently, it has also been recognized as the only facility in the U.S. currently capable of contributing to heavy ion radiotherapy research. This work contains a general overview of NSRL structure, capabilities and operation.

Validation of electromagnetic and hadronic physical processes in the interaction of a proton beam with matter: A Solar Particle Events case study with an Al slab

In the study of the effectiveness of shielding materials against radiations, one of the main steps concerns with the validation of models describing the interaction processes of the radiation of interest with the material chosen for the shielding. This paper shows the results of the validation of electromagnetic and hadronic processes with the aim to contribute to the study of protection for astronauts against the radiations due to the Solar Particle Events, in particular to the selection of the optimal material for radiation shielding. The physics case deals with the interaction of a proton beam with an aluminum slab about 20g/cm2 thick. Two specific applications, STP and DOSE, were developed by using Geant4 package. STP computes the radiations produced in the interaction and their stopping power; DOSE computes the absorbed dose from the stopping power calculated by STP. The validation process was performed in two steps. In the first one, the output of the STP code is compared to data available on NIST database; in the second one, the absorbed dose computed with DOSE is compared to the dose gathered during an experiment performed at the NASA Space Radiation Laboratory involving the bombardment of an aluminum slab with a 1GeV proton beam. The computing model has allowed us to correlate the size of the impinging beam profile to the dose measured before and after an Al slab. The sharp increase of the dose in the position right after the slab might be due to the stochastic nature of the trajectories of charged ions in matter which makes the radiation to emerge with non-zero transverse linear momentum. From the case examined here, we conclude that aluminum is not an efficient material for Solar Particle Event shielding.

SU‐C‐204‐04: Irradiation of Human Cell Lines Using Various Ions

Purpose:The purpose of this study is to investigate and quantify the biological effects of ion radiation using several human cell lines. We aim to answer the question of whether carbon ion the most ideal ion species for heavy ion radiotherapy.Methods:The cells were irradiated at different positions along the pristine Bragg peak of several ions with different atomic number. The biological effectiveness was evaluated using the clonogenic cell survival assay. Irradiation of three human lung cancer cell lines and a fibroblast cell line were undertaken using the charged particle beam at the NASA Space Radiation Laboratory at Brookhaven National Lab. Four mono‐energetic ion beams (carbon, oxygen, helium and lithium) were used to irradiate the cells. Water or media‐filled T25 flasks were lined up along the beam line so that the cell‐containing surfaces of the flasks were placed at a specific depth along the pristine Bragg curve. Four depths along the curve, representing entrance point, rising peak, peak and distal fall off, were selected to determine biological effectiveness. Gaf‐chromic films were placed between the flasks to monitor the irradiation as soon as it was finished.Results:For all ion radiations, the maximum cell killing effect occurs at either peak or distal fall off, depending on the cell lines. For instance, for the fibroblast cell line AGO1522, RBEs of 1.4, 1.2, 1.4 and 1.9 were observed at the Bragg peak for Helium, Lithium, Carbon and Oxygen ions. Comparing positions, RBEs of 0.9, 1.2, 1.4 and 1.8 were observed for carbon irradiation of AGO‐1522 cells positions corresponding to entrance, rising peak, peak and distal fall off.Conclusion:RBE values differ with position in the Bragg peak, ion species and cell line. Ions other than carbon may prove more effective in certain irradiation conditions and may contribute to optimized heavy ion therapy.

Use of the NASA Space Radiation Laboratory at Brookhaven National Laboratory to Conduct Charged Particle Radiobiology Studies Relevant to Ion Therapy

Although clinical studies with carbon ions have been conducted successfully in Japan and Europe, the limited radiobiological information about charged particles that are heavier than protons remains a significant impediment to exploiting the full potential of particle therapy. There is growing interest in the U.S. to build a cancer treatment facility that utilizes charged particles heavier than protons. Therefore, it is essential that additional radiobiological knowledge be obtained using state-of-the-art technologies and biological models and end points relevant to clinical outcome. Currently, most such ion radiotherapy-related research is being conducted outside the U.S. This article addresses the substantial contributions to that research that are possible at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), which is the only facility in the U.S. at this time where heavy-ion radiobiology research with the ion species and energies of interest for therapy can be done. Here, we briefly discuss the relevant facilities at NSRL and how selected charged particle biology research gaps could be addressed using those facilities.

Reference field specification and preliminary beam selection strategy for accelerator-based GCR simulation

The galactic cosmic ray (GCR) simulator at the NASA Space Radiation Laboratory (NSRL) is intended to deliver the broad spectrum of particles and energies encountered in deep space to biological targets in a controlled laboratory setting. In this work, certain aspects of simulating the GCR environment in the laboratory are discussed. Reference field specification and beam selection strategies at NSRL are the main focus, but the analysis presented herein may be modified for other facilities and possible biological considerations. First, comparisons are made between direct simulation of the external, free space GCR field and simulation of the induced tissue field behind shielding. It is found that upper energy constraints at NSRL limit the ability to simulate the external, free space field directly (i.e. shielding placed in the beam line in front of a biological target and exposed to a free space spectrum). Second, variation in the induced tissue field associated with shielding configuration and solar activity is addressed. It is found that the observed variation is likely within the uncertainty associated with representing any GCR reference field with discrete ion beams in the laboratory, given current facility constraints. A single reference field for deep space missions is subsequently identified. Third, a preliminary approach for selecting beams at NSRL to simulate the designated reference field is presented. This approach is not a final design for the GCR simulator, but rather a single step within a broader design strategy. It is shown that the beam selection methodology is tied directly to the reference environment, allows facility constraints to be incorporated, and may be adjusted to account for additional constraints imposed by biological or animal care considerations. The major biology questions are not addressed herein but are discussed in a companion paper published in the present issue of this journal. Drawbacks of the proposed methodology are discussed and weighed against alternative simulation strategies.

Galactic cosmic ray simulation at the NASA Space Radiation Laboratory

Most accelerator-based space radiation experiments have been performed with single ion beams at fixed energies. However, the space radiation environment consists of a wide variety of ion species with a continuous range of energies. Due to recent developments in beam switching technology implemented at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), it is now possible to rapidly switch ion species and energies, allowing for the possibility to more realistically simulate the actual radiation environment found in space. The present paper discusses a variety of issues related to implementation of galactic cosmic ray (GCR) simulation at NSRL, especially for experiments in radiobiology. Advantages and disadvantages of different approaches to developing a GCR simulator are presented. In addition, issues common to both GCR simulation and single beam experiments are compared to issues unique to GCR simulation studies. A set of conclusions is presented as well as a discussion of the technical implementation of GCR simulation.

Charged Particle Therapy with Mini-Segmented Beams.

One of the fundamental attributes of proton therapy and carbon ion therapy is the ability of these charged particles to spare tissue distal to the targeted tumor. This significantly reduces normal tissue toxicity and has the potential to translate to a wider therapeutic index. Although, in general, particle therapy also reduces dose to the proximal tissues, particularly in the vicinity of the target, dose to the skin and to other very superficial tissues tends to be higher than that of megavoltage x-rays. The methods presented here, namely, “interleaved carbon minibeams” and “radiosurgery with arrays of proton and light ion minibeams,” both utilize beams segmented into arrays of parallel “minibeams” of about 0.3 mm incident-beam size. These minibeam arrays spare tissues, as demonstrated by synchrotron x-ray experiments. An additional feature of particle minibeams is their gradual broadening due to multiple Coulomb scattering as they penetrate tissues. In the case of interleaved carbon minibeams, which do not broaden much, two arrays of planar carbon minibeams that remain parallel at target depth, are aimed at the target from 90° angles and made to “interleave” at the target to produce a solid radiation field within the target. As a result, the surrounding tissues are exposed only to individual carbon minibeam arrays and are therefore spared. The method was used in four-directional geometry at the NASA Space Radiation Laboratory to ablate a 6.5-mm target in a rabbit brain at a single exposure with 40 Gy physical absorbed dose. Contrast-enhanced magnetic resonance imaging and histology 6-month later showed very focal target necrosis with nearly no damage to the surrounding brain. As for minibeams of protons and light ions, for which the minibeam broadening is substantial, measurements at MD Anderson Cancer Center in Houston, TX, USA; and Monte Carlo simulations showed that the broadening minibeams will merge with their neighbors at a certain tissue depth to produce a solid beam to treat the target. The resulting sparing of proximal normal tissue allows radiosurgical ablative treatments with smaller impact on the skin and shallow tissues. This report describes these two methods and discusses their potential clinical applications.

Calcium and lithium ion production for laser ion source.

Calcium and lithium ion beams are required by NASA Space Radiation Laboratory at Brookhaven National Laboratory to simulate the effects of cosmic radiation. To identify the difficulties in providing such highly reactive materials as laser targets, both species were experimentally tested. Plate shaped lithium and calcium targets were fabricated to create ablation plasmas with a 6 ns 1064 nm neodymium-doped yttrium aluminum garnet laser. We found significant oxygen contamination in both the Ca and Li high charge state beams due to the rapid oxidation of the surfaces. A large spot size, low power density laser was used to create low charge state beams without scanning the targets. The low charge state Ca beam did not have any apparent oxygen contamination, showing the potential to clean the target entirely of oxide with a low power beam once in the chamber. The Li target was clearly still oxidizing in the chamber after each low power shot. To measure the rate of oxidation, we shot the low power laser at the target repeatedly at 10 s, 30 s, 60 s, and 120 s interval lengths, showing a linear relation between the interval time and the amount of oxygen in the beam.

Issues for Simulation of Galactic Cosmic Ray Exposures for Radiobiological Research at Ground-Based Accelerators.

For radiobiology research on the health risks of galactic cosmic rays (GCR) ground-based accelerators have been used with mono-energetic beams of single high charge, Z and energy, E (HZE) particles. In this paper, we consider the pros and cons of a GCR reference field at a particle accelerator. At the NASA Space Radiation Laboratory (NSRL), we have proposed a GCR simulator, which implements a new rapid switching mode and higher energy beam extraction to 1.5 GeV/u, in order to integrate multiple ions into a single simulation within hours or longer for chronic exposures. After considering the GCR environment and energy limitations of NSRL, we performed extensive simulation studies using the stochastic transport code, GERMcode (GCR Event Risk Model) to define a GCR reference field using 9 HZE particle beam–energy combinations each with a unique absorber thickness to provide fragmentation and 10 or more energies of proton and 4He beams. The reference field is shown to well represent the charge dependence of GCR dose in several energy bins behind shielding compared to a simulated GCR environment. However, a more significant challenge for space radiobiology research is to consider chronic GCR exposure of up to 3 years in relation to simulations with animal models of human risks. We discuss issues in approaches to map important biological time scales in experimental models using ground-based simulation, with extended exposure of up to a few weeks using chronic or fractionation exposures. A kinetics model of HZE particle hit probabilities suggests that experimental simulations of several weeks will be needed to avoid high fluence rate artifacts, which places limitations on the experiments to be performed. Ultimately risk estimates are limited by theoretical understanding, and focus on improving knowledge of mechanisms and development of experimental models to improve this understanding should remain the highest priority for space radiobiology research.

SU‐E‐T‐526: Irradiation of Human Cell Lines Using Carbon Ions: Real Time Dosimetry Using Gaf‐Chromic Film

Purpose:The purpose of this study is to investigate and quantify several factors affecting biological effects of carbon ions such as cell type, dose, energy and position where the cells are irradiated along the pristine Bragg curve.Methods:Experiments to quantify clonogenic cell survival in three human lung cancer cell lines and a fibroblast cell line were performed at the NASA Space Radiation Laboratory, BNL, Upton, USA. A system of water or media‐filled T25 flasks lined up along the beam axis was designed so that the cell‐containing surfaces of the flasks were placed at specific depths along the Bragg curve. Gaf‐chromic films were placed between the flasks to monitor the dose distribution in the sample as soon as the irradiation was finished. Additional studies were conducted at four selected depths along the Bragg curve to obtain full cell survival dose response curves for the four cell lines.Results:The percent depth dose of the beams was determined using an ionization chamber and showed that the physical Bragg peak is at 22.5 cm water depth. However, the clonogenic cell survival data indicated that the maximum cell killing occurred at 21.5 cm. Gaf‐chromic films revealed some inhomogeneity in the dose distribution on the flasks near the peak, presumably due to lack of scattering from the sides of the flasks, which might account for the differences. Depending on the cell line and radiation dose, the maximum cell killing (i.e., the greatest RBE) is at the 21.5 (the peak) or 24 cm (distal fall off) depth.Conclusion:There is a difference in biological effect along the Bragg curve of a carbon ion beam, indicating an elevated RBE at or beyond the end of the range. Gaf‐chromic films are proven to be effective in monitoring the 2D irradiation pattern to the flasks.Research supported by NIH/NCI through grant no. R21 CA182259.

Lack of reliability in the disruption of cognitive performance following exposure to protons.

A series of three replications were run to determine the reliability with which exposure to protons produces a disruption of cognitive performance, using a novel object recognition task and operant responding on an ascending fixed-ratio task. For the first two replications, rats were exposed to head-only exposures to 1000MeV/n protons at the NASA Space Radiation Laboratory. For the third replication, subjects were given head-only or whole-body exposures to both 1000 and 150MeV/n protons. The results were characterized by a lack of consistency in the effects of exposure to protons on the performance of these cognitive tasks, both within and between replications. The factors that might influence the lack of consistency and the implications for exploratory class missions are discussed.

Understanding cancer development processes after HZE-particle exposure: roles of ROS, DNA damage repair and inflammation.

During space travel astronauts are exposed to a variety of radiations, including galactic cosmic rays composed of high-energy protons and high-energy charged (HZE) nuclei, and solar particle events containing low- to medium-energy protons. Risks from these exposures include carcinogenesis, central nervous system damage and degenerative tissue effects. Currently, career radiation limits are based on estimates of fatal cancer risks calculated using a model that incorporates human epidemiological data from exposed populations, estimates of relative biological effectiveness and dose-response data from relevant mammalian experimental models. A major goal of space radiation risk assessment is to link mechanistic data from biological studies at NASA Space Radiation Laboratory and other particle accelerators with risk models. Early phenotypes of HZE exposure, such as the induction of reactive oxygen species, DNA damage signaling and inflammation, are sensitive to HZE damage complexity. This review summarizes our current understanding of critical areas within the DNA damage and oxidative stress arena and provides insight into their mechanistic interdependence and their usefulness in accurately modeling cancer and other risks in astronauts exposed to space radiation. Our ultimate goals are to examine potential links and crosstalk between early response modules activated by charged particle exposure, to identify critical areas that require further research and to use these data to reduced uncertainties in modeling cancer risk for astronauts. A clearer understanding of the links between early mechanistic aspects of high-LET response and later surrogate cancer end points could reveal key nodes that can be therapeutically targeted to mitigate the health effects from charged particle exposures.

Space radiation-associated lung injury in a murine model.

Despite considerable progress in identifying health risks to crewmembers related to exposure to galactic/cosmic rays and solar particle events (SPE) during space travel, its long-term effects on the pulmonary system are unknown. We used a murine risk projection model to investigate the impact of exposure to space-relevant radiation (SR) on the lung. C3H mice were exposed to (137)Cs gamma rays, protons (acute, low-dose exposure mimicking the 1972 SPE), 600 MeV/u (56)Fe ions, or 350 MeV/u (28)Si ions at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. Animals were irradiated at the age of 2.5 mo and evaluated 23.5 mo postirradiation, at 26 mo of age. Compared with age-matched nonirradiated mice, SR exposures led to significant air space enlargement and dose-dependent decreased systemic oxygenation levels. These were associated with late mild lung inflammation and prominent cellular injury, with significant oxidative stress and apoptosis (caspase-3 activation) in the lung parenchyma. SR, especially high-energy (56)Fe or (28)Si ions markedly decreased sphingosine-1-phosphate levels and Akt- and p38 MAPK phosphorylation, depleted anti-senescence sirtuin-1 and increased biochemical markers of autophagy. Exposure to SR caused dose-dependent, pronounced late lung pathological sequelae consistent with alveolar simplification and cellular signaling of increased injury and decreased repair. The associated systemic hypoxemia suggested that this previously uncharacterized space radiation-associated lung injury was functionally significant, indicating that further studies are needed to define the risk and to develop appropriate lung-protective countermeasures for manned deep space missions.

Effects of 28Si ions, 56Fe ions, and protons on the induction of murine acute myeloid leukemia and hepatocellular carcinoma.

Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the carcinogenic effects of 300 MeV/n 28Si or 600 MeV/n 56Fe ions in a mouse model for radiation-induced acute myeloid leukemia and hepatocellular carcinoma. C3H/HeNCrl mice were irradiated with 0.1, 0.2, 0.4, or 1 Gy of 300 MeV/n 28Si ions, 600 MeV/n 56Fe ions or 1 or 2 Gy of protons simulating the 1972 solar particle event (1972SPE) at the NASA Space Radiation Laboratory. Additional mice were irradiated with 137Cs gamma rays at doses of 1, 2, or 3 Gy. All groups were followed until they were moribund or reached 800 days of age. We found that 28Si or 56Fe ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia. However, 28Si or 56Fe ion irradiated mice had a much higher incidence of hepatocellular carcinoma than gamma ray irradiated or proton irradiated mice. These data demonstrate a clear difference in the effects of these HZE ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis. Also seen in this study was an increase in metastatic hepatocellular carcinoma in the 28Si and 56Fe ion irradiated mice compared with those exposed to gamma rays or 1972SPE protons, a finding with important implications for setting radiation exposure limits for space-flight crew members.

Biological characterization of low-energy ions with high-energy deposition on human cells.

During space travel, astronauts are exposed to cosmic radiation that is comprised of high-energy nuclear particles. Cancer patients are also exposed to high-energy nuclear particles when treated with proton and carbon beams. Nuclear interactions from high-energy particles traversing shielding materials and tissue produce low-energy (<10 MeV/n) secondary particles of high-LET that contribute significantly to overall radiation exposures. Track structure theories suggest that high charge and energy (HZE) particles and low-energy secondary ions of similar LET will have distinct biological effects for cellular and tissue damage endpoints. We investigated the biological effects of low-energy ions of high LET utilizing the Tandem Van de Graaff accelerator at the Brookhaven National Laboratory (BNL), and compared these to experiments with HZE particles, that mimic the space environment produced at NASA Space Radiation Laboratory (NSRL) at BNL. Immunostaining for DNA damage response proteins was carried out after irradiation with 5.6 MeV/n boron (LET 205 keV/μm), 5.3 MeV/n silicon (LET 1241 keV/μm), 600 MeV/n Fe (LET 180 keV/μm) and 77 MeV/n oxygen (LET 58 keV/μm) particles. Low-energy ions caused more persistent DNA damage response (DDR) protein foci in irradiated human fibroblasts and esophageal epithelial cells compared to HZE particles. More detailed studies comparing boron ions to Fe particles, showed that boron-ion radiation resulted in a stronger G2 delay compared to Fe-particle exposure, and boron ions also showed an early recruitment of Rad51 at double-strand break (DSB) sites, which suggests a preference of homologous recombination for DSB repair in low-energy albeit high-LET particles. Our experiments suggest that the very high-energy radiation deposition by low-energy ions, representative of galactic cosmic radiation and solar particle event secondary radiation, generates massive but localized DNA damage leading to delayed DSB repair, and distinct cellular responses from HZE particles. Thus, low-energy heavy ions provide a valuable probe for studies of homologous recombination repair in radiation responses.

Data Analysis of Tracks of Heavy Ion Particles in Timepix Detector

In this paper, we describe some of the computational challenges that need to be addressed when developing active Space Radiation Monitors and Dosimeters using the Timepix detectors developed by the Medipix2 Collaboration at CERN. Measurement of the Linear Energy Transfer (LET), the source and velocity of incident ionizing radiation, are of initial interest when developing such operational devices because they provide the capability to calculate the Dose-equivalent, and to characterize the radiation field for the design of radiation protective devices. In order to facilitate the LET measurement, we first propose a new method for calculating azimuth direction and polar angle of individual tracks of penetrating charged particles based on the pixel clusters they produce. We then describe an energy compensation method for heavy ion tracks suffering from saturation and plasma effects. Finally, we identify interactions within the detector that need to be excluded from the total effective Dose-Equivalent assessment. We make use of data taken at the HIMAC (Heavy Ion Medical Accelerator Center) facility in Chiba, Japan and NSRL (NASA Space Radiation Laboratory) at the Brookhaven National Laboratory in New York, USA for evaluation purposes.

Comparison of the Effects of Partial- or Whole-Body Exposures to16O Particles on Cognitive Performance in Rats

Studies using a ground-based system (NASA Space Radiation Laboratory) to examine the effects of exposure to high-energy charged particles or HZE particles on cognitive performance have interchangeably used whole-body exposures or exposures restricted to the head of the subject. For this study, we hypothesized that different types of exposure such as whole body vs. head only vs. body only might modulate the impact of irradiation on cognitive performance in different ways with the resulting cognitive performance outcomes being either independent of exposure type or strongly dependent on exposure type with each producing performance outcomes. To test these possibilities, three groups of rats were exposed to ¹⁶O particles (1,000 MeV/n): (1) head only; (2) body only; (3) whole body. Cognitive performance was measured using the elevated plus-maze, novel object recognition, spatial location memory and operant responding on an ascending fixed-ratio schedule. The results indicated that the performance of the rats on the spatial location memory task was markedly different when they received head-only irradiation compared to whole-body exposure. For the operant responding task, irradiation of the whole body resulted in a more severe performance decrement than exposures restricted to the head. The results are discussed in terms of nontargeted effects of HZE particles and the findings suggest that studies that utilize different patterns of exposure may not be directly comparable and that astronauts may be at a greater risk for HZE particle-induced cognitive deficits than previously thought.

Cognitive effects of partial and whole-body exposures to 16O particles

Introduction: When rats and mice are exposed to HZE particles at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory to simulate the effect of exposure to space radiation on cognitive performance, there may be differences in the amount of tissue that is irradiated: some experimenters irradiate only the head, whereas others irradiate the entire organism. Whether or not these different patterns of exposure have differential effects on cognitive performance remain to be established. Similarly, it remains to be established whether or not exposures restricted to the body can have an independent effect on cognitive performance.Radiation: Rats were exposed to 16O (1000 MeV/n; 1, 5, 10, 25 cGy) particles at the NSRL. There were three exposure conditions: head-only, body-only and whole body. Tungsten bricks were used to shield either the head or the body, as required. The bricks were removed for whole-body exposures. The non-irradiated control rats (0 cGy) were taken to the NSRL, but not exposed. Nominal dose rates were between 1 and 10 cGy/min, depending upon the total dose.Behavior: The animals were shipped to UMBC for behavioral testing. Cognitive performance was measured using the elevated-plus-maze (baseline anxiety); novel object recognition (general learning and memory); novel spatial location (spatial learning and memory); and operant responding on an ascending fixed-ratio schedule (motivation and responsiveness to environmental stimuli). The basis for the selection of the behavioral tests was that the behaviors are dopamine-mediated or show deterioration as a function of age.Results: The results of the experiments indicate that: (i) there may be differences in cognitive performance following exposure to either head-only or whole-body exposure to NASA-relevant doses of 16O particles depending on the specific task; and (ii) for some tasks, body-only exposures can disrupt neurocognitive performance. The results also suggest that exposures involving the body may influence the responsiveness of the organism to the disruptive effects of exposure to HZE particles on neurocognitive performance. This effect is seen in two ways: first, as a direct effect of body-only exposure on cognitive performance, as shown by decreased time spent in a novel location compared with non-irradiated controls, suggesting impaired spatial location memory; and second, as an interaction between head and body exposures seen with whole-body exposures.Discussion: These results indicate that body-only exposures have the potential to influence cognitive performance which is mediated by the brain. Although the mechanism remains to be fully established, it is possible that exposure of the body to HZE particles causes the release of cytokines which can affect neuronal function, either directly or through the mediation of the vagus nerve. As such, the results of studies using head-only or whole-body exposures may not be comparable. Also, astronauts may be subject to increased risk of deficits in cognitive performance during exploratory class missions.

Neuronal stress following exposure to 56Fe particles and the effects of antioxidant-rich diets

Exposing young rats to particles of high energy and charge (HZE particles), a ground-based model for exposure to cosmic rays, enhances indices of oxidative stress and inflammation and disrupts the functioning of neuronal communication in critical regions of the brain [ 1]. These changes in neuronal function are similar to those seen in ageing [ 2, 3]. Although there is some recovery of function after exposure to 56Fe particles, particularly in changes observed 36 h following irradiation, long-term changes (75 days) have been observed, suggesting subcellular damage. Consequently, oxidative stress and inflammation induced by radiation could affect downstream events, such as changes in behavior and gene expression. Therefore, berry fruits high in antioxidant and anti-inflammatory activity, such as blueberries and strawberries, may prevent the occurrence of neurochemical and behavioral changes that occur if fed prior to radiation [ 4].Rats were exposed to 56Fe (1000 MeV/n; 1.5 Gy) particles at the NASA Space Radiation Laboratory at Brookhaven National Laboratory; other rats served as non-irradiated controls. The animals were fed either a control or a 2% blueberry or strawberry diet 8 weeks prior to radiation. Rats were then either euthanized at 36 h (short term) or 30 days following irradiation (long term). Before and after the irradiation, the animals were housed at USDA Human Nutrition Research Center on Aging at Tufts University, Boston.The results of the experiments indicate that: (1) 56Fe exposure caused significant differential, neurochemical changes in critical regions of the brain, such as hippocampus, striatum, frontal cortex and cerebellum, particularly long term. (2) Neurochemical changes resulted in the disruption of autophagy, increased inflammation and increased oxidative stress protein markers. (3) Antioxidant-rich berry diets significantly reduced the accumulation of toxic cellular debris in critical regions of the brain, primarily at the 30 days post-irradiation time-point. (4) Susceptibility to inflammation, autophagy dysregulation, and oxidative stress were proportional to the levels of antioxidant enzymes in the respective brain regions. (5) Exposure to 56Fe radiation may cause the accumulation of disease-related proteins such as PHF-Tau, which has been implicated in the pathogenesis of Alzheimer's disease.Irradiation with 56Fe, which causes substantial build-up of toxic cellular debris in critical regions of the brain, may overwhelm the innate antioxidant enzyme defense system [ 5]. Therefore, berry diets high in antioxidants may be used to counter these damaging effects by reducing oxidative stress and inflammation, and activating neuronal housekeeping, in addition to boosting endogenous antioxidant enzymes.This paper was presented at the NASA Session at Heavy Ion in Therapy and Space Radiation Symposium 2013.