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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 NTRSDate not supplied

Neuroimmune responses to space radiation

One of the main health risks in human deep space exploration is central nervous system (CNS) damage by ionizing radiation due to exposure to galactic cosmic rays (GCRs). In animal models, irradiation with simulated GCRs or their components has been shown to cause neurodegeneration and neuroinflammation associated with cognitive and behavioral dysfunction. The extent of CNS damage is partially mediated by the blood-brain barrier (BBB), which regulates the interaction between CNS and systemic responses to stressors in the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal death, neuroinflammation and oxidative stress. However, studies on BBB and astrocyte functions in regulating CNS responses to ionizing radiation have been limited, especially in human tissue/organ analogs. Therefore, we developed a high-throughput 3D organ-on-a-chip system to study human CNS and BBB impairments caused by deep space radiation. We investigated both immediate and delayed CNS responses to major GCR components: 0.3-0.8Gy 600MeV/n 56Fe ions; as well as to 0.5-1Gy X-rays. We observed ionizing radiation-mediated increases in BBB permeability that was exacerbated by astrocyte presence and accompanied by damage to endothelial cells and tight junctions, altered cytokine expression including TNFalpha upregulation, and increased oxidative stress. In particular, 600MeV/n 56Fe particle irradiation selectively induced astrocyte damage and increased blood-brain barrier permeability only in models that contained astrocytes in addition to endothelial cells, indicating astrocytes as a particularly radiosensitive component of the CNS that could therefore be a suitable a target for neuroprotection. Future studies will compare human and mouse CNS model responses to simulated GCRs and evaluate the induction of an anti-inflammatory phenotype in astrocytes as a potential countermeasure. Furthermore, in our lab we have been exploring the individual variability, genomic associations and secreted biomarkers of responses to space radiation, which could eventually be combined to address personalized CNS health risk and develop individual countermeasures. Ultimately, we aim to expand upon these results to uncover novel cellular and mechanistic targets for countermeasure development to mitigate human CNS damage in deep space exploration.

space radiation↗
NASA NTRSDate not supplied

Neuroimmune Responses to Space Radiation

One of the main health risks in human deep space exploration is central nervous system (CNS) damage by ionizing radiation due to exposure to galactic cosmic rays (GCRs). In animal models, irradiation with simulated GCRs or their components has been shown to cause neurodegeneration and neuroinflammation associated with cognitive and behavioral dysfunction. The extent of CNS damage is partially mediated by the blood-brain barrier (BBB), which regulates the interaction between CNS and systemic responses to stressors in the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuronal death, neuroinflammation and oxidative stress. However, studies on BBB and astrocyte functions in regulating CNS responses to ionizing radiation have been limited, especially in human tissue/organ analogs. Therefore, we developed a high-throughput 3D organ-on-a-chip system to study human CNS and BBB impairments caused by deep space radiation. We investigated both immediate and delayed CNS responses to major GCR components: 600MeV/n 56Fe ions. We observed ionizing radiation-mediated dose-dependent increases in BBB permeability that was exacerbated by astrocyte presence and accompanied by altered cytokine expression including interleukin-1 receptor alpha downregulation, and increased oxidative stress. In particular, 600MeV/n 56Fe particle irradiation selectively increased damage and blood-brain barrier permeability only in models that contained astrocytes in addition to endothelial cells, indicating astrocytes as a particularly radiosensitive component of the CNS that could therefore be a suitable a target for neuroprotection. Future studies will compare human and mouse CNS model responses to simulated GCRs and evaluate the induction of an anti-inflammatory phenotype in astrocytes as a potential countermeasure. Furthermore, in our lab we have been exploring the individual variability, genomic associations and secreted biomarkers of responses to space radiation, which could eventually be combined to address personalized CNS health risk and develop individual countermeasures. Ultimately, we aim to expand upon these results to uncover novel cellular and mechanistic targets for countermeasure development to mitigate human CNS damage in deep space exploration.

space radiation↗
NASA NTRSDate not supplied

NASA Space Radiation Laboratory Galactic Cosmic Ray Simulator

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 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 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 helium ions (~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 2-6 weeks, with individual beam fractions as low as 0.1-0.2 mGy. In the large beam configuration (60 x 60 cm2), 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 will deepen our understanding of the numerous health risks faced by astronauts. This talk discusses NASA’s innovative technology solution for a ground-based GCR simulator at the NASA Space Radiation Laboratory to enable future exploration missions.

galactic cosmic ray simulator↗
NASA NTRSDate not supplied

Neurobehavioral Effects Of Five-Ion GCRSim Exposure In Male And Female Mice

Exposure to space galactic cosmic radiation is a principal consideration of spaceflight missions, and with upcoming missions to the Moon and Mars, it is increasingly imperative to elucidate the detrimental effects of space travel beyond the lower Earth orbit. Additionally, with the first female astronaut to soon travel to the Moon and beyond lower Earth orbit, there is a strong need to understand the biological sex differences to adaptation to the deep space environment. While the effects of spaceflight on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. Therefore, we investigated the neurobehavioral responses to space environment-like radiation exposure. Male and female 23–24-week-old mice (age-matched to average astronaut age) were exposed to 5, 15 and 50 cGy via Five-Ion Galactic Cosmic Ray Simulation at the NASA National Space Radiation Laboratory at Brookhaven National Laboratory. Both early (72hrs post exposure) and late (1-4 months post exposure) cognitive and behavioral deficits were investigated. In-cage behavior was analyzed as frequency/duration of digging, rearing, and grooming and nestlet building using a 5-stage Deacon score. Additionally, at NASA Ames, behavior tests included Catwalk (gait), Zero Maze (anxiety), Adhesive Removal (sensory motor), Novel Object Recognition and Barnes Maze (working memory). There were pronounced sex differences in both early and late time points. Females typically performed the tests better than males, specifically in nestlet building, gait and working memory, though males performed better at the sensory motor (adhesive removal) test. Dose effects were primarily observed at 50 cGy for both sexes, particularly with the Barnes Maze (working memory), where both males and females exposed to 50 cGy showed little to no improvement in test performance, though females again performed better than males. Currently, we are investigating the correlations between the observed behavior and cytokine levels in the plasma and brain. Future studies will continue to investigate cognitive consequences of galactic cosmic radiation in combination with other space-like environment stressors, including antigravity and social versus single housing.

Stephanie Puukila↗
NASA NTRSDate not supplied

Early And Late Neurobehavioral Effects Of Male And Female Mice Exposed To Five-Ion GCRSim

With upcoming missions to the Moon and beyond to Mars, it is increasingly imperative to elucidate the detrimental effects of space travel beyond the lower Earth orbit, particularly to galactic cosmic radiation. Additionally, with the first female astronaut to soon travel to the Moon there is a strong need to understand the biological sex differences to adaptation to the deep space environment. While the effects of spaceflight on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. Here, we investigated the neurobehavioral responses to space environment-like radiation exposure. Male and female 23–24-week-old mice (age-matched to average astronaut age) were exposed to 5, 15 and 50 cGy via Five-Ion Galactic Cosmic Ray Simulation at the NASA National Space Radiation Laboratory at Brookhaven National Laboratory. Both early (72hrs post exposure) and late (1-4 months post exposure) cognitive and behavioral deficits were investigated. Early analysis was performed by observing in-cage behavior including frequency/duration of digging, rearing, and grooming and nestlet building. Additionally, late effects were analyzed at NASA Ames via in-cage behavior as well as Catwalk (gait), Zero Maze (anxiety), Adhesive Removal (sensory motor), Novel Object Recognition and Barnes Maze (working memory). There were pronounced sex differences in both early and late time points. Females scored better than males in nestlet building, gait and working memory while males scored better at the sensory motor (adhesive removal) test. Dose effects were primarily observed at 50 cGy for both sexes, particularly with the Barnes Maze (working memory), where both males and females exposed to 50 cGy showed little to no improvement in test performance, though females again performed better than males. Currently, we are investigating the correlations between the observed behavior and cytokine levels in the plasma and brain. Future studies will continue to investigate cognitive consequences of galactic cosmic radiation in combination with other space-like environment stressors, including antigravity and social versus single housing.

S Puukila↗
NASA NTRSDate not supplied

Neurobehavioral Effects Of Five-Ion GCRSim Exposure In Male And Female Mice

Exposure to space galactic cosmic radiation is a principal consideration of spaceflight missions, and with upcoming missions to the Moon and Mars, it is increasingly imperative to elucidate the detrimental effects of space travel beyond the lower Earth orbit. Additionally, with the first female astronaut to soon travel to the Moon and beyond lower Earth orbit, there is a strong need to understand the biological sex differences to adaptation to the deep space environment. While the effects of spaceflight on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. Therefore, we investigated the neurobehavioral responses to space environment-like radiation exposure. Male and female 23–24-week-old mice (age-matched to average astronaut age) were exposed to 5, 15 and 50 cGy via Five-Ion Galactic Cosmic Ray Simulation at the NASA National Space Radiation Laboratory at Brookhaven National Laboratory. Both early (72hrs post exposure) and late (1-4 months post exposure) cognitive and behavioral deficits were investigated. In-cage behavior was analyzed as frequency/duration of digging, rearing, and grooming and nestlet building using a 5-stage Deacon score. Additionally, at NASA Ames, behavior tests included Catwalk (gait), Zero Maze (anxiety), Adhesive Removal (sensory motor), Novel Object Recognition and Barnes Maze (working memory). There were pronounced sex differences in both early and late time points. Females typically performed the tests better than males, specifically in nestlet building, gait and working memory, though males performed better at the sensory motor (adhesive removal) test. Dose effects were primarily observed at 50 cGy for both sexes, particularly with the Barnes Maze (working memory), where both males and females exposed to 50 cGy showed little to no improvement in test performance, though females again performed better than males. Currently, we are investigating the correlations between the observed behavior and cytokine levels in the plasma and brain. Future studies will continue to investigate cognitive consequences of galactic cosmic radiation in combination with other space-like environment stressors, including antigravity and social versus single housing.

S. Puukila↗
NASA NTRSDate not supplied

Effects Of Five-Ion Galactic Cosmic Radiation Simulation On Immune Function, Brain, And Behavior In Male And Female Mice

Exposure to galactic cosmic radiation is a principal consideration of spaceflight missions, and with upcoming missions to the Moon and Mars, it is increasingly imperative to elucidate the effects of space travel beyond the lower Earth orbit. Additionally, with the first female astronaut to soon travel to the Moon there is a strong need to understand the biological sex differences to adaptation to the deep space environment. While the effects of spaceflight on the nervous system are not fully known, studies in animal models have shown that exposure to ionizing radiation can cause neuronal damage and lead to downstream cognitive and behavioral deficits. To simulate the type of radiation exposure occurring during spaceflight, model organisms can be exposed to relevant doses via Five-Ion Galactic Cosmic Radiation Simulation at the NASA National Space Radiation Laboratory at Brookhaven National Laboratory. We have investigated the neurobehavioral responses to space environment-like radiation exposure. Male and female 23–24-week-old mice (age-matched to average astronaut age) were exposed to 5, 15 and 50 cGy. Following exposure, immune, brain and behavioral (sensorimotor, risk-taking and cognitive) measures were acquired at ‘Acute’ (IR+24hrs, IR+72hrs), ‘Intermediate’ (IR+14 days) and ‘Delayed’ (IR+28 to IR+124 days) to inform biological responses anticipated during a transit to Moon and Mars. There were pronounced sex differences observed in all outcome measurements, while very few radiation induced effects were observed. Those dose effects that were observed were primarily in cytokine expression and less so in behavioral measurements. Further studies will investigate if radiation, microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure/function, and neurobehavioral/cognitive performance, ultimately to characterize risks and identify appropriate countermeasures in both women and men in anticipation of future deep space missions.

Stephanie Puukila↗
NASA NTRSDate not supplied

Transcriptomic Analysis of ISS Crewmembers’ Peripheral Blood Mononuclear Cells Reveals Homeostatic Regulations in Space

The impact of spaceflight on the immune system has been investigated for decades. Studies conducted in cell models, animals and humans suggest that the spaceflight environment affects the innate and acquired immune systems, as the ability to recognize antigens, defend against foreign invaders, and orchestrate repair is significantly hindered. However, the molecular mechanisms behind spaceflight-induced immune dysregulations are still unclear. In this study, blood from eleven (11) International Space Station (ISS) crewmembers was collected before, during and after long duration space missions, as well as from 11 matched ground control subjects. Transcriptomic analysis was performed in isolated peripheral blood mononuclear cells (PBMCs) using the RNA-sequencing technique. In comparison to the blood samples collected from the crewmembers pre-flight, a total of ~1000 genes were found to be upregulated and ~1000 genes downregulated in PBMC collected between 4 and 6 months after they were in space. The most significantly DEGs (differentially expressed genes) include activation of RUBCNL which is an autophagy enhancer and inhibition of GRASP which regulates cell trafficking. Genes involved in cell adhesion, cell cycle progression and other functions were also dysregulated. Pathway analysis of the DEGs indicates mitochondria dysfunction, particularly reduced ATP production in the electron transport chain. Other pathways impacted by spaceflight include glycolysis, autophagy and inflammatory response. Our results suggest that, in space, blood cells may have also experienced energy depletion and reduced metabolism. Consequently, the cells may become autophagic, which is a known homeostatic mechanism for blood cells to become quiescent, but to stay alive. Further analysis of the data shows recovery of the crewmembers after mission and potential differential responses between genders to the space environment. Our data potentially explains some of the physiological changes that have been observed in space such as mitochondria dysfunction, inhibition of T cell activation and telomere lengthening. Comparison of our results with other transcriptomics studies of ISS crewmembers’ blood cells will also be presented.

Maria Moreno Villanueva↗
NASA NTRS1996

Calbindins decreased after space flight

Exposure of the body to microgravity during space flight causes a series of well-documented changes in Ca2+ metabolism, yet the cellular and molecular mechanisms leading to these changes are poorly understood. Calbindins, vitamin D-dependent Ca2+ binding proteins, are believed to have a significant role in maintaining cellular Ca2+ homeostasis. In this study, we used biochemical and immunocytochemical approaches to analyze the expression of calbindin-D28k and calbindin-D9k in kidneys, small intestine, and pancreas of rats flown for 9 d aboard the space shuttle. The effects of microgravity on calbindins in rats from space were compared with synchronous Animal Enclosure Module controls, modeled weightlessness animals (tail suspension), and their controls. Exposure to microgravity resulted in a significant and sustained decrease in calbindin-D28k content in the kidney and calbindin-D9k in the small intestine of flight animals, as measured by enzyme-linked immunosorbent assay (ELISA). Modeled weightlessness animals exhibited a similar decrease in calbindins by ELISA. Immunocytochemistry (ICC) in combination with quantitative computer image analysis was used to measure in situ the expression of calbindins in the kidney and the small intestine, and the expression of insulin in pancreas. There was a large decrease of immunoreactivity in renal distal tubular cell-associated calbindin-D28k and in intestinal absorptive cell-associated calbindin-D9k of space flight and modeled weightlessness animals compared with matched controls. No consistent difference in pancreatic insulin immunoreactivity between space flight, modeled weightlessness, and controls was observed. Regression analysis of results obtained by quantitative ICC and ELISA for space flight, modeled weightlessness animals, and their controls demonstrated a significant correlation. These findings after a short-term exposure to microgravity or modeled weightlessness suggest that a decreased expression of calbindins may contribute to the disorders of Ca2+ metabolism induced by space flight.

Non-NASA Center↗
NASA NTRS1987

Comparative aspects of hematological responses in animal and human models in simulations of weightlessness and space flight

This paper reviews some human and animal responses to space flight as well as in control models in simulations of weightlessness. Astronauts after space flight have been found to have a decreased red blood cell mass and plasma volume. The reason for these changes is unknown but appears to be caused primarily by a decrease in the need of red blood cells in the weightless condition. Similar though more moderate changes have been found in human subjects subjected to prolonged bed rest or water immersion. What happens to the red cell mass of laboratory rats flown in microgravity is not known but rats have shown an increase in the rate of random red cell loss in flight suggesting a probable decrease. Rat models subjected to either head-down suspension or restraint alone have shown a decrease in red blood cell masses and a decrease in their plasma volume.

Lange, R. D.↗
NASA NTRS1989

Human task animation from performance models and natural language input

Graphical manipulation of human figures is essential for certain types of human factors analyses such as reach, clearance, fit, and view. In many situations, however, the animation of simulated people performing various tasks may be based on more complicated functions involving multiple simultaneous reaches, critical timing, resource availability, and human performance capabilities. One rather effective means for creating such a simulation is through a natural language description of the tasks to be carried out. Given an anthropometrically-sized figure and a geometric workplace environment, various simple actions such as reach, turn, and view can be effectively controlled from language commands or standard NASA checklist procedures. The commands may also be generated by external simulation tools. Task timing is determined from actual performance models, if available, such as strength models or Fitts' Law. The resulting action specification are animated on a Silicon Graphics Iris workstation in real-time.

Esakov, Jeffrey↗
NASA NTRS1979

Part-body and multibody effects on absorption of radio-frequency electromagnetic energy by animals and by models of man

Fine structure in the whole-body resonant curve for radio-frequency energy deposition in man can be attributed to part-body resonances. As for head resonance, which occurs near 350 MHz in man, the absorptive cross section is nearly three times the physical cross section of the head. The arm has a prominent resonance at 150 MHz. Numerical solutions, antenna theory, and experimental results on animals have shown that whole-body energy deposition may be increased by 50 percent or more because of multiple bodies that are strategically located in the field. Empirical equations for SARs are also presented along with test data for several species of laboratory animals. Barbiturate anesthesia is sufficiently disruptive of thermoregulation that delta Ts of colonic temperature yield energy dose values in several mammals that compare quite favorably with those based on whole-body calorimetry.

Gandhi, O. P.↗
NASA NTRS1987

Animated computer graphics models of space and earth sciences data generated via the massively parallel processor

The capability was developed of rapidly producing visual representations of large, complex, multi-dimensional space and earth sciences data sets via the implementation of computer graphics modeling techniques on the Massively Parallel Processor (MPP) by employing techniques recently developed for typically non-scientific applications. Such capabilities can provide a new and valuable tool for the understanding of complex scientific data, and a new application of parallel computing via the MPP. A prototype system with such capabilities was developed and integrated into the National Space Science Data Center's (NSSDC) Pilot Climate Data System (PCDS) data-independent environment for computer graphics data display to provide easy access to users. While developing these capabilities, several problems had to be solved independently of the actual use of the MPP, all of which are outlined.

Treinish, Lloyd A.↗
NASA NTRS2004

Lessons from Immune 1-3: what did we learn and what do we need to do in the future?

Sprague-Dawley rats were subjected to three 8-to-10 day space flights on the Space Shuttle. Housed in NASA's Animal Enclosure Modules, rats were flown to test the hypotheses that therapy with pegylated interleukin-2 or insulin-like growth factor-1 would ameliorate some of the effects of space flight on the immune system. As part of these experiments, we measured body and organ weights, blood cell differentials, plasma corticosterone, macrophage colony forming units, lymphocyte mitogenic, super-antigenic and interferon-gamma responses, bone marrow cell and peritoneal macrophage cytokine secretion and bone strength and mass. This paper compares some of the immunophysiological parameters of the control animals used in the Immune1-3 flight series and presents data from an animal infection model for use during space flight.

short duration↗
NASA NTRS2014

Oxidative Stress Responses to Simulated Spaceflight in Mineralized and Marrow Compartments of Bone and Associated Vasculature

Long-term spaceflight causes profound changes to the musculoskeletal system attributable to unloading and fluid shifts in microgravity. Future space explorations beyond the earth’s magnetosphere will expose astronauts to space radiation, which may cause additional skeletal deficits that are not yet fully understood. Our long-term goals are twofold: to define the mechanisms and risk of bone loss in the spaceflight environment and to facilitate the development of effective countermeasures if necessary. Our central hypothesis is that oxidative stress plays a key role in progressive bone loss and vascular dysfunction caused by spaceflight. In animal’s models, overproduction of free radicals is associated with increased bone resorption, lower bone formation, and decrements in bone mineral density and structure which can ultimately lead to skeletal fragility. Evidence in support of a possible causative role for oxidative stress in spaceflight-induced bone loss derive from knockout and transgenic mouse studies and the use of pharmacological interventions with known anti-oxidant properties. In our studies to simulate spaceflight, 16-wk old, male C56Bl/6J mice were assigned to one of four groups: hind limb unloading to simulate weightlessness (HU), normally loaded Controls (‘NL’) (sham irradiated, no hind limb unloading), irradiated at NASA Space Radiation Laboratory ‘IR’ with 1-2Gy of (600MeV/n) alone, or in combination with protons (0.5Gy Protons/0.5Gy 56Fe), (IR) or both hind limb unloaded and irradiated, ‘HU+IR’. Mice were exposed to radiation 3 days after initiating HU and tissues harvested were 1-14 days after initiating treatments for analyses. Results from our laboratories, which employ various biochemical, gene expression, functional, and transgenic animal model methods, implicate dynamic regulation of redox-related pathways by spaceflight-related environmental factors. As one example, we found that combined HU and radiation exposure caused oxidative damage in skeletal tissues (lipid peroxidation) of wildtype mice, whereas bone from transgenic mice that overexpress human catalase in mitochondria were protected. Interestingly, marrow cells grown under culture conditions that select for endothelial progenitor cells (EPC), showed that HU but not IR reduced EPC cell migration; in contrast HU and IR each inhibited growth of marrow-derived osteoblast progenitors. Taken together, these results indicate that unloading and ionizing elicit distinct effects on progenitor and mature cells of vascular and skeletal tissue, and that oxidative damage may contribute to skeletal and vascular deficits that may emerge during extended space travel.

Globus, R. K.↗
NASA NTRS1992

Animation of finite element models and results

This is not intended as a complete review of computer hardware and software that can be used for animation of finite element models and results, but is instead a demonstration of the benefits of visualization using selected hardware and software. The role of raw computational power, graphics speed, and the use of videotape are discussed.

Lipman, Robert R.↗
NASA NTRS1986

Different reactivity to angiotensin II of peripheral and renal arteries in spontaneously hypertensive rats: effect of acute and chronic angiotensin converting enzyme inhibition

We assessed renal blood flow and pressor responses to graded angiotensin II doses in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats ingesting a diet containing 1.6% sodium basally and after acute and chronic angiotensin converting enzyme (ACE) inhibition with captopril. In the basal state the pressor response to angiotensin II was enhanced (P<0.0005) and the renal vascular response was blunted (P<0.005) in SHR compared with WKY rats. After acute captopril administration the pressor response was enhanced in both strains, and the difference between them was maintained, while the renal vascular response was enhanced in both, but more in SHR, so that the renal vascular response in the SHR became larger than in WKY (P<0.0001). Chronic captopril treatment blunted both pressor and renal responses in WKY rats, but only the pressor response in SHR. The renal vessels of SHR seem to be different from those of WKY rats in reaction to exogenous angiotensin II, and in response to both acute administration of captopril (probably acting through blockade of angiotensin II production) and chronic administration of captopril (probably acting mainly through accumulation of kinin or production of prostaglandins).

NASA Discipline Number 21-50↗