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

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At least 181 records · Page 10
All sourcesNASA NTRSDOE OSTI
NASA NTRS1987

Growth factor involvement in tension-induced skeletal muscle growth

New muscle tissue culture techniques were developed to grow embryonic skeletal myofibers which are able to differentiate into more adultlike myofibers. Studies on mechanical simulation of cultured muscle cell growth will now be more directly applicable to mechanically-induced growth in adult muscle, and lead to better models for understanding muscle tissue atrophy caused by disuse in the microgravity of space.

Vandenburgh, Herman W.↗
NASA NTRS2017

So You Want to Go to Mars: Bones and Matters of the Heart

There is evidence that weightlessness and radiation, two elements of the spaceflight environment, can lead to detrimental changes in human musculoskeletal tissue, including bone loss and muscle atrophy. This bone loss is thought to be brought about by the increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. Collectively, our research team aims to understand the molecular mechanisms underlying the responses of mammalian tissue to the spaceflight environment using earth-based animal and cellular models. The overarching goal is to identify molecular targets to prevent tissue decrements induced by spaceflight and earth-based scenarios of radiotherapy, accidental radiation exposure and reduced mobility. In this talk, I will provide an overview of skeletal and cardiovascular responses to spaceflight and will highlight our research progress on understanding the role of reactive oxygen species (ROS) signaling in skeletal responses to radiation and simulated weightlessness.

heart↗
NASA NTRS2004

Exo-Skeletal Engine: Novel Engine Concept

The exo-skeletal engine concept represents a new radical engine technology with the potential to substantially revolutionize engine design. It is an all-composite drum-rotor engine in which conventionally heavy shafts and discs are eliminated and are replaced by rotating casings that support the blades in spanwise compression. Thus the rotating blades are in compression rather than tension. The resulting open channel at the engine centerline has immense potential for jet noise reduction and can also accommodate an inner combined-cycle thruster such as a ramjet. The exo-skeletal engine is described in some detail with respect to geometry, components, and potential benefits. Initial evaluations and results for drum rotors, bearings, and weights are summarized. Component configuration, assembly plan, and potential fabrication processes are also identified. A finite element model of the assembled engine and its major components is described. Preliminary results obtained thus far show at least a 30-percent reduction of engine weight and about a 10-dB noise reduction, compared with a baseline conventional high-bypass-ratio engine. Potential benefits in all aspects of this engine technology are identified and tabulated. Quantitative assessments of potential benefits are in progress.

Chamis, Cristos C.↗
NASA NTRS1999

Is skeletal muscle ready for long-term spaceflight and return to gravity?

It is now clear that prevention of muscle debilitation during spaceflight will require a broader approach than simple exercise aimed at strengthening of the muscle fibers. The levels of several hormones and receptors are altered by unloading and must be returned to homeostasis. Pharmacotherapy and gene transfer strategies to raise the relative level of structural proteins may minimize the problems faced by astronauts in readapting to Earth-gravity. Up to now, we have only minimally exploited microgravity for advancing our understanding of muscle biology. A research laboratory in the space station with a centrifuge facility (gravity control) is essential for conducting basic research in this field. Microgravity has proven an excellent tool for noninvasively perturbing the synthesis of muscle proteins in the search for molecular signals and gene regulatory factors influencing differentiation, growth, maintenance and atrophy of muscle. Understanding the relation between blood flow and interstitial edema and between workload and subsequent structural failure are but two important problems that require serious attention. The roles of hormones and growth factors in regulating gene expression and their microgravity-induced altered production are other urgent issues to pursue. These types of studies will yield information that advances basic knowledge of muscle biology and offers insights into countermeasure design. This knowledge is likely to assist rehabilitation of diseased or injured muscles in humans on Earth, especially individuals in the more vulnerable aging population and persons participating in strenuous sports. Will the skeletal muscle system be prepared for the increased exposure to microgravity and the return to gravity loading without injury when space station is operational? The answer depends in large part on continued access to space and funding of ground-based models and flight experiments. The previous two decades of spaceflight research have described the effects of microgravity on multiple systems. The next generation of experiments promises to be even more exciting as we are challenged to define the cellular and molecular mechanisms of microgravity-induced changes.

manned↗
NASA NTRS1996

Response of the neuromuscular unit to spaceflight: what has been learned from the rat model

Despite the inherent limitations placed on spaceflight investigations, much has been learned about the adaptations of the neuromuscular system to weightlessness from studies of rats flown for relatively short periods (approximately 4-22 days). Below is a summary of the major effects of spaceflight observed in muscles of rats that are not in their rapid growth stage: 1. Skeletal muscles atrophy rapidly during spaceflight; significant atrophy is observed as early as after 4 days of flight. 2. The atrophic response appears to be related to the primary function of the muscle. In the hindlimb, the relative amount of atrophy can be characterized as slow extensors > fast extensors > fast flexors. This pattern of relative atrophy does not appear to be occurring in the forelimb; however, not enough data are available to draw any definitive conclusions at this time. 3. Both slow and fast fibers atrophy during spaceflight, with the largest fibers within an individual muscle generally showing the greatest atrophic response. Interestingly, the amount of fiber atrophy appears to reach a plateau after about 14 days of flight. 4. Adaptations have been observed in the concentration and content of all muscle proteins pools, with the protein pools in slow muscles the most affected. 5. Some slow and fast fibers in predominantly slow and fast muscles show shifts in their histochemical and biochemical properties, toward those observed in a "faster" phenotype. 6. Some fibers, presumably expressing slow MHC isoforms before flight, begin to express fast MHC isoforms during flight. 7. The oxidative capacity of the muscles or fibers is relatively unaffected by spaceflight, particularly in the slow muscles. Any change in whole-body fatigability associated with spaceflight most likely reflects the loss in muscle and fiber mass. 8. The glycolytic capacity of the muscles and muscle fibers is enhanced after spaceflight. This metabolic adaptation seems to be related to the shift in the contractile proteins towards "faster" isoforms. 9. The vascularity of muscles appears to be maintained after flight, based, at least, on histological observations of capillarity. 10. The force capabilities of the muscles and fibers appear to decrease in parallel with the decreases in size, i.e., the specific tension is not significantly affected after flight. 11. Changes in the speed-related properties of the slow muscles are consistent with the adaptations in the myosin molecule, i.e., the slow muscles and some fibers in the slow muscles become "faster." 12. Some muscle fiber and neuromuscular junction damage has been observed after flight, particularly in the slow muscles. The extent of damage may be related to the amount of time that the muscles are allowed to reload before removal, i.e., in general, shorter intervals result in less fiber damage. 13. Adaptations in the motor (ventral horn) and sensory (spinal ganglia) neurons have been quite variable, but this may be related to the amount of time that the muscles are allowed to reload before removal. Morphological adaptations after relatively short periods of reloading may reflect a decrease in the activation of the neural elements during flight.

manned↗
NASA NTRS2018

Redox Signaling and Its Impact on Skeletal and Vascular Responses to Spaceflight

Spaceflight entails exposure to numerous environmental challenges with the potential to contribute to both musculoskeletal and vascular dysfunction. The purpose of this review is to describe current understanding of microgravity and radiation impacts on the mammalian skeleton and associated vasculature at the level of the whole organism. Recent experiments from spaceflight and groundbased models have provided fresh insights into how these environmental stresses influence mechanisms that are related to redox signaling, oxidative stress, and tissue dysfunction. Emerging mechanistic knowledge on cellular defenses to radiation and other environmental stressors, including microgravity, are useful for both screening and developing interventions against spaceflight-induced deficits in bone and vascular function.

redox siggnalin↗
NASA NTRS1984

Morphological and histochemical studies of bone and cartilage during periods of stimulated weightlessness

Rats which were subjected to spaceflight for 2-4 weeks showed considerable loss in ability to form new bone. Animals which are placed into nonweight bearing positions, as a model to simulate the absence of gravity here on the Earth's surface. Show a similar decline in new bone formation. It is suggested that the mechanisms underlying these changes may be the result of reduced transmission of gravitational force to the skeletal cells.

Doty, S. B.↗
NASA NTRS2006

An Optimization of Pulsed ElectroMagnetic Fields Study

To date, in our research we have focused on the use of normal human neuronal progenitor (NHNP) cells because of their importance in human nervous system regeneration, development and maintenance, but we have developed 2-D and 3-D bioreactors that can accommodate any cell line. In this Project, we will include the use of tissues important for physiological regeneration: Human osteoblasts or chondrocytes, and vascular cells. Our initial results with the NHNP cells were quite startling using extremely low-level electromagnetic fields (5 microtesla at 10Hz; 6mA). The low-amplitude, rapidly time-varying electromagnetic fields exert a very potent effect on the proliferation, morphology, and gene expression of the cells in culture, both in standard 2-dimensional culture plates as well as cells organized into 3-dimensional tissue-like assemblies (TLAs) in a 3D bioreactor. We have replicated our preliminary results many, many times, have analyzed the gene expression using gene arrays (followed by Luminex analysis for protein production), and have monitored cell proliferation, orientation, morphology, and glucose metabolism, and we are confident that we have a stable and reliable model to study the control of high-level cellular processes by application of low-amplitude, time varying electromagnetic fields (TVEMF) (1, 2). In additional studies at the University of Michigan, we have been able to generate functional in vitro engineered mammalian skeletal muscle, and have employed nerve-muscle co-culture techniques to promote axonal sprouting. We believe that nearly all tissues, in particular, neural, are susceptible to the influences of low-level TVEMF.

Goodwin, Thomas J.↗
NASA NTRS1999

Novel Receptor-Based Countermeasures to Microgravity-Induced Bone Loss

The biological actions mediated by the estrogen receptor (ER), vitamin D receptor (VDR) and Ca(sup 2+) (sub o) -sensing receptor (CaR) play key roles in the normal control of bone growth and skeletal turnover that is necessary for skeletal health. These receptors act by controlling the differentiation and/or function of osteoblasts and osteoclasts, and other cell types within the bone and bone marrow microenvironment. The appropriate use of selective ER modulators (SERMS) which target bone, vitamin D analogs that favor bone formation relative to resorption, and CaR agonists may both stimulate osteoblastogenesis and inhibit osteoclastogenesis and the function of mature osteoclasts, should make it possible to prevent the reduction in bone formation and increase in bone resorption that normally contribute to the bone loss induced by weightlessness. Indeed, there may be synergistic interactions among these receptors that enhance the actions of any one used alone. Therefore, we proposed to: 1) assess the in vitro ability of novel ER, VDR and CaR agonists, alone or in combination, to modulate osteoblastogenesis and mature osteoblast function under conditions of 1g and simulated microgravity; 2) assess the in vitro ability of novel ER, VDR and CaR agonists, alone or in combination, to modulate osteoclastogenesis and bone resorption under conditions of lg and simulated microgravity; and 3) carry out baseline studies on the skeletal localization of the CaR in normal rat bone as well as the in vivo actions of our novel ER- and VDR-based therapeutics in the rat in preparation for their use, alone or in combination, in well-established ground-based models of microgravity and eventually in space flight.

OMalley, Bert W.↗
NASA NTRS2016

Effects of Zoledronate and Mechanical Loading during Simulated Weightlessness on Bone Structure and Mechanical Properties

Space flight modulates bone remodeling to favor bone resorption. Current countermeasures include an anti-resorptive drug class, bisphosphonates (BP), and high-force loading regimens. Does the combination of anti-resorptives and high-force exercise during weightlessness have negative effects on the mechanical and structural properties of bone? In this study, we implemented an integrated model to mimic mechanical strain of exercise via cyclical loading (CL) in mice treated with the BP Zoledronate (ZOL) combined with hindlimb unloading (HU). Our working hypothesis is that CL combined with ZOL in the HU model induces additive structural and mechanical changes. Thirty-two C57BL6 mice (male,16 weeks old, n8group) were exposed to 3 weeks of either HU or normal ambulation (NA). Cohorts of mice received one subcutaneous injection of ZOL (45gkg), or saline vehicle, prior to experiment. The right tibia was axially loaded in vivo, 60xday to 9N in compression, repeated 3xweek during HU. During the application of compression, secant stiffness (SEC), a linear estimate of slope of the force displacement curve from rest (0.5N) to max load (9.0N), was calculated for each cycle once per week. Ex vivo CT was conducted on all subjects. For ex vivo mechanical properties, non-CL left femurs underwent 3-point bending. In the proximal tibial metaphysis, HU decreased, CL increased, and ZOL increased the cancellous bone volume to total volume ratio by -26, +21, and +33, respectively. Similar trends held for trabecular thickness and number. Ex vivo left femur mechanical properties revealed HU decreased stiffness (-37),and ZOL mitigated the HU stiffness losses (+78). Data on the ex vivo Ultimate Force followed similar trends. After 3 weeks, HU decreased in vivo SEC (-16). The combination of CL+HU appeared additive in bone structure and mechanical properties. However, when HU + CL + ZOL were combined, ZOL had no additional effect (p0.05) on in vivo SEC. Structural data followed this trend with ZOL not modulating trabecular thickness in CL + NAHU mice. In summary, our integrated model simulates the combination of weightlessness, exercise-induced mechanical strain, and anti-resorptive treatment that astronauts experience during space missions. Based on these results, we conclude that, at the structural and stiffness level, zoledronate treatment during simulated spaceflight does not impede the skeletal response to axial compression. In contrast to our hypothesis, our data show that zoledronate confers no additional mechanical or structural benefit beyond those gained from cyclical loading.

Mechanical Loading↗
NASA NTRS1998

Perspective on the impact of weightlessness on calcium and bone metabolism

As humans venture into space to colonize the moon and travel to distant planets in the 21st century, they will be confronted with a bone disease that could potentially limit their space exploration activities or put them at risk for fracture when they return to earth. It is now recognized that an unloading of the skeleton, either due to strict bed rest or in zero gravity, leads on average to a 1%-2% reduction in bone mineral density at selected skeletal sites each month. The mechanism by which unloading of the skeleton results in rapid mobilization of calcium stores from the skeleton is not fully understood, but it is thought to be related to down regulation in PTH and 1,25-dihydroxyvitamin D3 production. Bone modeling and mineralization in chick embryos is not affected by microgravity, suggesting that bone cells adapt and ultimately become addicted to gravity in order to maintain a structurally sound skeleton. Strategies need to be developed to decrease microgravity-induced bone resorption by either mimicking gravity's effect on bone metabolism, or enhancing physically or pharmacologically bone formation in order to preserve astronauts' bone health.

short duration↗
NASA NTRS2001

The Spacelab 3 simulation: basis for a model of growth plate response in microgravity in the rat

Data from Spacelab 3 (SL3) suggested that spaceflight significantly reduces the activity of the rat tibial growth plate. Animal processing after SL3 began twelve hours post-landing, so data reflect post-flight re-adaptation in addition to spaceflight effects. To determine if a twelve-hour period of weight bearing after seven days of unloading could affect the physes of spaceflown rats, the present study assessed the growth plate response to unloading with or without a reloading period. Rats were subjected to hind-limb suspension for seven days and then euthanized, with or without twelve hours of reloading. Activity of the growth plate was assessed by morphometric analysis. Rats suspended without reloading had reserve zone (RZ) height greater than controls, and shorter hypertrophy/calcification zone (HCZ) with fewer cells. The greater RZ was associated with a larger cell area, indicating a possible mitotic delay or secretion defect. Twelve hours of reloading decreased RZ height and cell number, and restored the number of cells in HCZ to control values, but the number of cells in the proliferative zone and height in HCZ were reduced. These results suggest the rebound response to preserve/restore skeletal function after a period of unloading involves an acceleration of growth associated with a decreased cell cycle time in PZ. Changes during the reloading period in this simulation support our hypothesis that the effects of spaceflight on SL3 growth plates were altered by changes that occurred post-landing. The similarities in response to unloading by suspension or during spaceflight are used to propose a model of growth plate response during spaceflight.

manned↗
NASA NTRS2018

Effects of Mitochondrial-Targeted Human Catalase in Skeletal Tissue of Mice Exposed to Simulated Spaceflight

During prolonged spaceflight, astronauts are exposed to both microgravity and space radiation and are at risk forincreased skeletal fragility due to bone loss, Evidence from rodent experiments has established that bothmicrogravity and ionizing radiation can cause bone loss due to increasd of bone-resorbing osteoclasts and decreasedin bone-forming osteoblasts, although the underlying molecular mechanisms for these changes are not fullyunderstood. We hypothesized that excess reactive oxidative species (ROS) produced by conditions that simulatedspaceflight alters the tight balance between osteoclast and osteoblast activities, leading to accelerated skeletalremodeling and culminating in loss of mineralized tissue. To begin to explore this hypothesis, we used the mCATmouse model [1]; these transgenic mice over-express the human catalase gene targeted to mitochondria, which arethe major organelle responsible for cellular production of free radicals. Catalase is an anti-oxidant that catalyzes theconversion of the reactive species, hydrogen peroxide (H202), into water and oxygen. This animal model wasselected as it displays extended lifespan, reduced cardiovascular disease and reduced central nervous systemradiosensitivity, consistent with elevated anti-oxidant activity conferred by the transgene. We reasoned that miceoverexpressing catalase the mitochondria of osteoblast and osteoclast lineage cells would be protected from the boneloss caused by simulated spaceflight.

CATALASE IN SKELETAL TISSUE↗
NASA NTRS1984

Atrophy and growth failure of rat hindlimb muscles in tail-cast suspension

The primary objective of the present study is related to an evaluation of a modified tail-cast suspension model as a means of identifying metabolic factors which control or are associated with muscle atrophy and growth failure. Two different control conditions (normal and tail-casted weight bearing) were studied to determine the appropriate control for tail-cast suspension. A description is presented of a model which is most useful for studying atrophy of hindlimb muscles under certain conditions. Female Sprague-Dawley rats were employed in the experiments. Attention is given to growth rate and urinary excretion of urea and ammonia in different types of rats, the relationship between body weight and skeletal muscle weight, and the relationship between animal body weight and rates of protein synthesis and protein degradation.

Jaspers, S. R.↗
NASA NTRS1994

Comparison of the Physiology of the Spaceflight and Hindlimb Suspended Rat

The suspended rat has been used extensively as a simulation of the spaceflight animal. In suspension, hindlimbs are unloaded from the acceleration of gravity, much as they are in spaceflight. Comparisons of data from spaceflight (microgravity) and suspended (1G) rats have suggested that suspension my be an appropriate model, but no direct comparisons had been made between the spaceflight and suspended rat. Cosmos 2044 afforded the first opportunity to directly compare the effects of hindlimb suspension (HS) and spaceflight (SF) on a broad range of physiological and histological parameters. This paper reports on the comparison of skelton, skeletal muscle, heart, neural, pulmonary, kidney, liver, intestine, blood plasma, immune function, red blood cells, and endocrine and reproductive functions and systems.

Grindeland, R. E.↗
NASA NTRS2001

The molecular responses of skeletal muscle satellite cells to continuous expression of IGF-1: implications for the rescue of induced muscular atrophy in aged rats

Approximately 50% of humans older than 85 years have physical frailty due to weak skeletal muscles. This indicates a need for determining mechanisms to combat this problem. A critical cellular factor for postnatal muscle growth is a population of myogenic precursor cells called satellite cells. Given the complex process of sarcopenia, it has been postulated that, at some point in this process, a limited satellite cell proliferation potential could become rate-limiting to the regrowth of old muscles. It is conceivable that if satellite cell proliferative capacity can be maintained or enhanced with advanced age, sarcopenia could potentially be delayed or prevented. Therefore, the purposes of this paper are to describe whether IGF-I can prevent muscular atrophy induced by repeated cycles of hindlimb immobilization, increase the in vitro proliferation in satellite cells from these muscles and, if so, the molecular mechanisms by which IGF-I mediates this increased proliferation. Our results provide evidence that IGF-I can enhance aged muscle regrowth possibly through increased satellite cell proliferation. The results also suggest that IGF-I enhances satellite cell proliferation by decreasing the cell cycle inhibitor, p27Kip1, through the PI3'-K/Akt pathway. These data provide molecular evidence for IGF-I's rescue effect upon aging-associated skeletal muscle atrophy.

NASA Discipline Musculoskeletal↗
NASA NTRS1996

The Role of Musculoskeletal Dynamics and Neuromuscular Control in Stress Development in Bone

The role of forces produced by the musculotendon units in the stress development of the long bones during gait has not been fully analyzed. It is well known that the musculotendons act as actuators producing the joint torques which drive the body. Although the joint torques required to perform certain motor tasks can be recovered through a kinematic analysis, it remains a difficult problem to determine the actual forces produced by each muscle that resulted in these torques. As a consequence, few studies have focused on the role of individual muscles in the development of stress in the bone. This study takes a control theoretic approach to the problem. A seven-link, eight degrees of freedom model of the body is controlled by various muscle groups on each leg to simulate gait. The simulations incorporate Hill-type models of muscles with activation and contraction dynamics controlled through neural inputs. This direct approach allows one to know the exact muscle forces exerted by each musculotendon throughout the gait cycle as well the joint torques and reaction forces at the ankle and knee. Stress and strain computed by finite element analysis on skeletal members will be related to these derived loading conditions. Thus the role of musculoskeletal dynamics and neuromuscular control in the stress development of the tibia during gait can be analyzed.

DeWoody, Yssa↗