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At least 181 records · Page 10

The NASA Space Radiation Health Program

The NASA Space Radiation Health Program is a part of the Life Sciences Division in the Office of Space Science and Applications (OSSA). The goal of the Space Radiation Health Program is development of scientific bases for assuring adequate radiation protection in space. A proposed research program will determine long-term health risks from exposure to cosmic rays and other radiation. Ground-based animal models will be used to predict risk of exposures at varying levels from various sources and the safe levels for manned space flight.

Schimmerling, W.↗

Self Motion Perception and Motion Sickness

The studies conducted in this research project examined several aspects of motion sickness in animal models. A principle objective of these studies was to investigate the neuroanatomy that is important in motion sickness with the objectives of examining both the utility of putative models and defining neural mechanisms that are important in motion sickness.

Fox, Robert A.↗

Neural Connectivity and Immunocytochemical Studies of Anatomical Sites Related to Nauseogenic and Emetic Reflexes

The studies conducted in this research project examined several aspects of neuroanatomical structures and neurochemical processes related to motion sickness in animal models. A principle objective of these studies was to investigate neurochemical changes in the central nervous system that are related to motion sickness with the objective of defining neural mechanisms important to this malady. For purposes of exposition, the studies and research finding have been classified into five categories. These are: immunoreactivity in the brainstem, vasopressin effects, lesion studies of area postrema, role of the vagus nerve, and central nervous system structure related to adaptation to microgravity.

Fox, Robert A.↗

Role of Dendritic Cells in Immune Dysfunction

Specific aims include: (1) Application of the bioreactor to enhance cytokine-regulated proliferation and maturation of dendritic cells (DC); (2) Based on clues from spaceflight: compare the frequency and function of DC in normal donors and immunocompromised cancer patients; and (3) Initiate studies on the efficiency of cytokine therapy and DC-assisted immunotherapy (using bioreactor-expanded DC) in animal models of experimental fungal infections.

Savary, Cherylyn A.↗

Baroreflex Function in Rats after Simulated Microgravity

Prolonged exposure of humans to decreased gravitational forces during spaceflight results in a number of adverse cardiovascular consequences, often referred to as cardiovascular deconditioning. Prominent among these negative cardiovascular effects are orthostatic intolerance and decreased exercise capacity. Rat hindlimb unweighting is an animal model which simulates weightlessness, and results in similar cardiovascular consequences. Cardiovascular reflexes, including arterial and cardiopulmonary baroreflexes, are required for normal adjustment to both orthostatic challenges and exercise. Therefore, the orthostatic intolerance and decreased exercise capacity associated with exposure to microgravity may be due to cardiovascular reflex dysfunction. The proposed studies will test the general hypothesis that hindlimb unweighting in rats results in impaired autonomic reflex control of the sympathetic nervous system. Specifically, we hypothesize that the ability to reflexly increase sympathetic nerve activity in response to decreases in arterial pressure or blood volume will be blunted due to hindlimb unweighting. There are 3 specific aims: (1) To evaluate arterial and cardiopulmonary baroreflex control of renal and lumbar sympathetic nerve activity in conscious rats subjected to 14 days of hindlimb unweighting; (2) To examine the interaction between arterial and cardiopulmonary baroreflex control of sympathetic nerve activity in conscious hindlimb unweighted rats; (3) to evaluate changes in afferent and/or central nervous system mechanisms in baroreflex regulation of the sympathetic nervous system. These experiments will provide information related to potential mechanisms for orthostatic and exercise intolerance due to microgravity.

Hasser, Eileen M.↗

Cardiovascular Session Summary

It was apparent that the bed-rest and spaceflight data indicated that decreases in plasma volume and cardiac atrophy along with cardiac remodeling were fundamental changes which predisposed many astronauts to post flight orthostatic intolerance. Despite the recently acquired in-flight and post-flight muscle sympathetic nerve activity findings suggesting that the sympathetic nerve responses were appropriate there remains significant contrary data from bed-rest studies, post- flight stand tests and hind-limb unweighted rat studies that suggest that the vasoconstrictive responses were compromised at least insufficient in susceptible individuals. The key issues raised is whether a diminished increase in sympathetic activity from baseline without changes in 254 First Biennial Space Biomedical Investigators'Workshop Cardiovascular peak response or receptor adaptations is an abnormal response or is an individual variance of response to the accentuated decrease in stroke volume. Data relating autonomic neural control of heart rate were presented to suggest that the vagal and sympathetic control of heart rate was attenuated. Also, bed-rest and space flight induced attenuated baroreflex control of heart rate was shown to be restored to pre-bedrest function by one bout of maximal dynamic exercise. However, these data were confounded by relying on the use of R-R interval as a measure of efferent responses of the baroreflex during a condition in which the baseline heart rate was changed. Clearly the idea that the autonomic control of heart rate may be changed by microgravity needs further investigation. This direction is suggested despite the fact that in the triple product (HR x SV x TPR = MAP) assessment of the regulation of arterial blood pressure during orthostasis the role of the HR reflex may be less influential than that associated. with cardiac atrophy (SV changes) and aberrant sympathetic vasoconstriction (resistance) changes. Although sympathetic nerve activity responses in-flight and post-flight on neurolab appeared appropriate, enough bed-rest and post-flight stand test data, along with animal model data suggest that vasoconstriction was compromised. The mechanism of this compromised vasoconstriction needs to be delineated. Other major findings concerning microgravity and physiological regulatory systems are that: I . Thermoregulatory adaptation appear to suggest some decrements in the control of cutaneous vasodilation and sweating; 2. Calcium resorption and dietary calcium need to be defined for differing durations of spaceflight, especially as the effects of excess calcium on vasomotor function appears to be detrimental; 3. Neurohumoral mechanisms of microgravity induced changes in neural function and the regulation of plasma volume and total body water, bone resorption and autonomic neural control of the circulation need further delineation; 4. As performance of work tasks become prolonged, the mechanisms of blood pressure regulation in microgravity needs to be used in the recovery period from prolonged work tasks.

Raven, Peter↗

Chemoprevention of Radiation Induced Rat Mammary Neoplasms

Radiations encountered in space include protons and heavy ions such as iron as well as their secondaries. The relative biological effect (RBE) of these ions is not known, particularly at the doses and dose-rates expected for planetary missions. Neutrons, are not particularly relevant to space travel, but have been found experimentally to have an increase in their RBE with decreasing dose. If a similar trend of increasing RBE with decreasing dose is present for heavy ions and protons during irradiation in space, the small doses received during space travel could potentially have substantial carcinogenic risk. Clearly more investigation of the effects of heavy ions and protons is needed before accurate risk assessment for prolonged travel in space can be done. One means to mitigate the increased risk of cancer due to radiation exposure in space is by developing effective countermeasures that can reduce the incidence of tumor development. Tamoxifen has recently been shown to be an effective chemopreventive agent in both animal models and humans for the prevention of mammary tumors. Tamoxifen is a unique drug, with a highly specific mechanism of action affecting a specific radiation-sensitive population of epithelial cells in the mammary gland. In human studies, the annual incidence of a primary tumor in the contralateral breast of women with previous breast cancer is about 8 per 1000, making them an exceedingly high-risk group for the development of breast cancer. In this high risk group, treated with tamoxifen, daily, for 2 years, the incidence of a new primary tumor in the contralateral breast was approximately one third of that noted in the non-tamoxifen treatment group. Tamoxifen antagonizes the action of estrogen by competing for the nuclear receptor complex thereby altering the association of the receptor complex and nuclear binding sites. Its effects in reducing the development of breast cancer could be accomplished by controlling clinically undetectable microcancers, arresting preneoplastic lesions, or correcting abnormal environments which predispose to high risk of malignant transformation.

Huso, David L.↗

Effects of Spaceflight and Hindlimb Suspension on the Posture and Gait of Rats

Instability of posture and gait in astronauts following spaceflight (SF) is thought to result from muscle atrophy and from changes in sensory-motor integration in the CNS (central nervous system) that occur during adaptation to microgravity (micro-G). Individuals are thought to have developed, during SF, adaptive changes for the processing of proprioceptive, vestibular and visual sensory inputs with reduced weighting of gravity-based signals and increased weighting of visual and tactile cues. This sensory-motor rearrangement in the CNS apparently occurs to optimize neuromuscular system function for effective movement and postural control in micro-G. However, these adaptive changes are inappropriate for the 1 g environment and lead to disruptions in posture and gait on return to Earth. Few reports are available on the effects of SF on the motor behavior of animals. Rats studied following 18.5 - 19.5 days of SF in the COSMOS program were described as being ..'inert, apathetic, slow'.. and generally unstable. The hindlimbs of these rats were ..'thrust out from the body with fingers pulled apart and the shin unnaturally pronated'. On the 6th postflight day motor behavior was described as similar to that observed in preflight observations. Improved understanding of the mechanisms leading to these changes can be obtained in animal models through detailed analysis of neural and molecular mechanisms related to gait. To begin this process the posture and gait of rats were examined following exposure to either SF or hindlimb suspension (HLS), and during recovery from these conditions.

Fox, R. A.↗

Case Descriptions and Observations About Cutis Marmorata From Hypobaric Decompressions

There is disagreement about the pathophysiology, classification, and treatment of cutis marmorata (CM), so there is disagreement about the disposition and medical status of a person that had CM. CM is rare, associated with stressful decompressions, and may be associated with serious signs and symptoms of decompression sickness (DCS). CM presents as purple or bluish-red skin mottling, often in the pectoral region, shoulders, chest, or upper abdomen. It is unethical to induce CM in humans so all information comes from retrospective analysis of case reports, or from animal models. A literature search, seven recent case reports from the Johnson Space Center and Brooks Air Force Base Hypobaric DCS Databases, interviews with DCS treatment experts, and responses to surveys provided the factual information used to arrive at our conclusions and recommendations. The "weight of evidence" indicates that CM is a local, not centrally mediated or systemic response to bubbles. It is unclear whether obstruction of arterial or venous blood flow is the primary insult since the lesion is reported under either condition. Any neurological or cardiovascular involvements are coincidental, developing along the same time course. The skin could be the source of the bubbles due to its mass, the associated layer of fat, and the variable nature of skin blood flow. CM should not be categorized as Type II DCS, should be included with other skin manifestations in a category called cutaneous DCS, and hyperbaric treatment is only needed if ground level oxygen is ineffective in the case of altitude-induced CM.

Conkin, Johnny↗

Space Biosensor Systems: Implications for Technology Transfer

To meet the need for continuous, automated monitoring of animal subjects, including; humans, during space flight, NASA is developing advanced physiologic sensor and biotelemetry system technologies. The ability to continuously track basic physiological parameters, such as heart rate, blood pH, and body temperature, in untethered subjects in space is a challenging task. At NASA's Ames Research Center, where a key focus is gravitational biology research, engineers have teamed with life scientists to develop wireless sensor systems for automated physiologic monitoring of animal models as small as the rat. This technology is also being adapted, in collaboration with medical professionals, to meet human clinical monitoring needs both in space and on the ground. Thus, these advanced monitoring technologies have important dual-use functions; they meet space flight data collection requirements and constraints, while concurrently addressing a number of monitoring and data acquisition challenges on the ground in areas of clinical monitoring and biomedical research. Additional applications for these and related technologies are being sought and additional partnerships established that enhance development efforts, reduce costs and facilitate technology infusion between the public and private sectors. This paper describes technology transfer and co-development projects that have evolved out of NASA's miniaturized, implantable chemical sensor development efforts.

Hines, J. W.↗

Regulatory Mechanism of Muscle Disuse Atrophy in Adult Rats

During the last phase of NAG 2-386 we completed three studies. The effects of 14 days of weightlessness; the vastus medialis (VM) from flight rats in COSMOS 2044 was compared with the VM from tail suspended rats and other controls. The type I and II fibers in the mixed fiber portion of the VM were significantly reduced in flight rats and capillary densities paralleled the fiber density changes. The results of this project compared favorably with those in the extensor digitorum longus following seven days of flight in SL 3. The cardiovascular projects focused on the blood pressure changes in head down tilted rats (HDT) and non-head down tilted (N-HDT) rats. Blood pressures (MAP, SP and DP) were significantly elevated through seven days of HDT and rapidly returned to control levels within one day after removal from the HDT position. The N-HDT showed some slight rise in blood pressure but these were not as great and they were not as rapid. The HDT rats were characterized as exhibiting transient hypertension. These results led to some of the microvascular and vascular graduate student projects of Dr. Bernhard Stepke. Also our results refute or, at least, do not agree with previous reports from other laboratories. Each animal, in our blood pressure projects, served as its own control thereby providing more accurate results. Also, our experiments focused on recovery studies which can, in and of themselves, provide guidelines for flight experiments concerned with blood pressure changes. Another experiment was conducted to examine the role of testicular atrophy in whole body suspended (WBS) and tail suspended (TS) rats. We worked in conjunction with Dr. D.R. Deaver's laboratory at Pennsylvania State University and Dr. R. P. Amann at Colorado State University. In the TS rats the testes are retracted into the abdominal cavity, unless a ligature is placed to maintain them in the external scrotal sac. The cryptorchid condition in TS rats results in atrophy of the testes and lowered levels of spermatid formation. Hormonal changes due to testes atrophy must be considered in future experiments where related effects may modify muscle, bone or other tissue changes. Also, some new assessments of past results (published by many researchers) may warrant revised interpretations. The blood pressure studies and the testicular function results were presented and reviewed during an invited lecture at the University of Bordeaux II during the Animals in Space Symposium in March 1993. In summary, each of these three projects complied with the objectives of the proposal and serve to demonstrate the utility of animal models in preparations and interpretations of space flight results. All funding has been expended in accordance with the approved budget.

Source record↗

Skeletal Phenotype of Transgenic Mice Expressing the Beta1 Integrin Cytoplasmic Tail In Osteoblasts

To define the physiologic role of beta1 integrin in bone formation and mechanical loading, transgenic mice were generated by expressing the cytoplasmic tall and transmembrane domain of Beta1 integrin under the control of the osteocalcin promoter. In cultured cells, this truncated fragment of Beta1 can act as a dominant negative. Previously, the matrix of calvariae was shown to be abnormal in transgenic (TG) compared to wildtype (WT) mice. In this study, we analyzed appendicular bone in TG and WT, male and female mice at 14, 35, 63, 90 and 365 days old (n=8-12/gp). To assess beta1 integrin function in mechanical loading, a pilot study using hindlimb unloading by tail suspension was performed. 35d old TG and WT females were hindlimb unloaded for 4 wks (n=3-5). Body mass, bone mineral content, histomorphometric (distal femur) and biomechanical parameters were analyzed. Statistical significance (P less than.05) was defined by ANOVA using the Tukey-Kramer post-hoc test. We confirmed transgene expression by immunoprecipitating then immunoblotting bone lysates using an antibody against the beta1 tail. Body masses of TG mice at 63, 90 and 365d old were greater (16-25%) than WT. Some TG female mice at 365d appeared obese; mean abdominal fat mass was 415% greater in TG than WT mice. Tibiae were longer (5-7%) in TG than WT mice at 63 and 90d. Tibial mineral mass of 35d males was 7% lower in TG than WT mice, but at 63d was 21% higher. The % osteoblast surface in 35d TG mice was 20% higher than WT, and at 63d was 17% lower, while % osteoclast surface did not differ. In 365d mice, cancellous bone volume (125%) and endocortical mineral apposition rate (40%) were greater in TG than WT males but not females. In WT mice, hindlimb unloading caused a reduction in mineral mass of tibiae (-20%) and lumbar vertebrae (-22%) relative to normally loaded controls. Surprisingly, hindlimb unloading also caused a relative reduction (-13%) in humerus mass. The effects of hindlimb unloading on tibia and humerus mass were less obvious in TG than in WT mice. Since hindlimb unloading caused skeletal changes in both loaded and unloaded bones, systemic changes may contribute to bone responses observed using this animal model. In conclusion, transgene expression resulted in marked metabolic changes during growth and in the aged female. Our results demonstrate that expression of the Beta1 integrin cytoplasmic tail in vivo causes gender- and age-specific changes in select morphometric parameters, bone length, and bone mass.

Globus, R. K.↗

Understanding How Space Travel Affects Blood Vessels: Arterial Remodeling and Functional Adaptations Induced by Microgravity

Ever rise quickly from the couch to get something from the kitchen and suddenly feel dizzy? With a low heart rate and relaxed muscles, the cardiovascular system does not immediately provide the resistance necessary to keep enough blood going to your head. Gravity wins, at least for a short time, before your heart and blood vessels can respond to the sudden change in position and correct the situation. Actually, the human cardiovascular system is quite well adapted to the constant gravitational force of the Earth. When standing, vessels in the legs constrict to prevent blood from collecting in the lower extremities. In the space environment, the usual head-to-foot blood pressure and tissue fluid gradients that exist during the upright posture on Earth are removed. The subsequent shift in fluids from the lower to the upper portions of the body triggers adaptations within the cardiovascular system to accommodate the new pressure and fluid gradients. In animal models that simulate microgravity, the vessels in the head become more robust while those in the lower limbs become thin and lax. Similar changes may also occur in humans during spaceflight and while these adaptations are appropriate for a microgravity environment, they can cause problems when the astronauts return to Earth or perhaps another planet. Astronauts often develop orthostatic intolerance which means they become dizzy or faint when standing upright. This dizziness can persist for a number of days making routine activities difficult. In an effort to understand the physiological details of these cardiovascular adaptations, Dr. Michael Delp at Texas A&M University, uses the rat as a model for his studies. For the experiment flown on STS-107, he will test the hypothesis that blood vessels in the rats' hindlimbs become thinner, weaker, and constrict less in response to pressure changes and to chemical signals when exposed to microgravity. In addition, he will test the hypothesis that arteries in the brain become thicker as a result of microgravity-induced fluid shifts toward the head.

Delp, Michael↗

The Hematopoietic Stem Cell Therapy for Exploration of Deep Space

It is hypothesized that the hematopoietic stem cell therapy (HSCT) might countermeasure various space-caused disorders so as to maintain astronauts' homeostasis. If this were achievable, the HSCT could promote human exploration of deep space. Using animal models of disorders (hindlimb suspension unloading system and beta-thalassemia), the HSCT was tested for muscle loss, immunodeficiency and space anemia. The results indicate feasibility of HSCT for these disorders. To facilitate the HSCT in space, growth of HSCs were optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

Ohi, Seigo↗

Space Radiation Hazards and Countermeasures: 1990-2004

Contents include the folowing: radiation environments, tools and techniques for measuring radiation dosage, effects of radiation on humans and animal models, methods for strengthening biological resistance to radiation, and radiation shielding.

Source record↗

Space flight nutrition research: platforms and analogs

Conducting research during actual or simulated weightlessness is a challenging endeavor, where even the simplest activities may present significant challenges. This article reviews some of the potential obstacles associated with performing research during space flight and offers brief descriptions of current and previous space research platforms and ground-based analogs, including those for human, animal, and cell-based research. This review is intended to highlight the main issues of space flight research analogs and leave the specifics for each physiologic system for the other papers in this section.

NASA Discipline Regulatory Physiology↗