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At least 91 records · Page 5

Slow Wave Sleep and Long Duration Spaceflight

While ground research has clearly shown that preserving adequate quantities of sleep is essential for optimal health and performance, changes in the progression, order and /or duration of specific stages of sleep is also associated with deleterious outcomes. As seen in Figure 1, in healthy individuals, REM and Non-REM sleep alternate cyclically, with stages of Non-REM sleep structured chronologically. In the early parts of the night, for instance, Non-REM stages 3 and 4 (Slow Wave Sleep, or SWS) last longer while REM sleep spans shorter; as night progresses, the length of SWS is reduced as REM sleep lengthens. This process allows for SWS to establish precedence , with increases in SWS seen when recovering from sleep deprivation. SWS is indeed regarded as the most restorative portion of sleep. During SWS, physiological activities such as hormone secretion, muscle recovery, and immune responses are underway, while neurological processes required for long term learning and memory consolidation, also occur. The structure and duration of specific sleep stages may vary independent of total sleep duration, and changes in the structure and duration have been shown to be associated with deleterious outcomes. Individuals with narcolepsy enter sleep through REM as opposed to stage 1 of NREM. Disrupting slow wave sleep for several consecutive nights without reducing total sleep duration or sleep efficiency is associated with decreased pain threshold, increased discomfort, fatigue, and the inflammatory flare response in skin. Depression has been shown to be associated with a reduction of slow wave sleep and increased REM sleep. Given research that shows deleterious outcomes are associated with changes in sleep structure, it is essential to characterize and mitigate not only total sleep duration, but also changes in sleep stages.

Whitmire, Alexandra↗

The Effects of CDKN1a/p21 on Oxidative Stress and Mitochondrial Function During Long Duration Spaceflight

Broad tissue degeneration and the failure of normal tissue regenerative processes in microgravity because of mechanical unloading are increasing concerns for sustaining life in space as the duration of future flight missions increases. Work in our laboratory has identified normal adult stem cell-based tissue regenerative processes, such as the formation of new bone, cartilage, and immune cells, as being particularly sensitive to the stresses of mechanical unloading in microgravity. Our studies have also identified the inhibition of differentiation of marrow mesenchymal stem cells and activation of CDKN1ap21-mediated cell cycle arrest in proliferative osteoprecursor cells on the bone surface as potential mechanisms for spaceflight-induced skeletal changes. This finding, in combination with the role of CDKN1ap21 as a suppressor of mammalian tissue regeneration, suggests that this gene could be responsible for suppressing stem cell-based tissue regeneration in response to disuse. In this work, we hypothesized that CDKN1ap21 regulates regenerative bone formation in response to alterations in mechanical load and tested this hypothesis by studying the skeletal phenotype and stem cell regenerative ability of juvenile (4-11 weeks old) and adult (18 weeks-12 months old) p21 (--) knockout (KO) mice. Additionally, we analyzed bone micro-architectural properties, bone formation rates and differentiation capacity of bone marrow stem cells (BMSCs) from male and female KO mice exposed to hindlimb unloading (HU) for 15-30 days. We found that juvenile KO mice exhibited increased femoral trabecular and cortical bone formation, whilst three-point bending of the tibias from KO mice showed decreased bone stiffness. Conversely, adult KO mice exhibited no significant differences in micro-architectural properties compared to WT (wild-type) but woven bone structure was indicative of rapid bone remodeling. Furthermore, cortical bone properties showed similar characteristics to aged bone, including increased cross-sectional area and perimeter, whilst three-point bending showed increased stiffness and toughness. Interestingly, in-vitro, KO mice exhibited increased differentiation and mineralized nodule formation in osteoblastogenesis assays compared to WT. Preliminary results from CDKN1ap21 KO mice subjected to HU suggest altered sensitivity to mechanical unloading resulting in decreased cortical thickness compared to WT mice. However, KO mice subjected to short and long-duration HU show increased in-vitro differentiation potential of BMSCs to from form mature, mineral-forming osteoblasts, indicating maintenance of regenerative potential. Analysis of bone formation rates, cell proliferation rates and key genes of interest are currently underway. These results indicate a novel role for CDKN1ap21 in load-dependent osteoprogenitor proliferation and differentiation and that deletion of CDKN1ap21 results in an age-dependent release of osteoblast proliferation inhibition and increased bone formation and turnover.

Stem Cells↗

Development of Countermeasures to Aid Functional Egress from the Crew Exploration Vehicle Following Long Duration Spaceflight

Astronauts experience disturbances in sensorimotor function following their return to Earth due to adaptive responses that occur during exposure to the microgravity conditions of space flight. As part of the Crew Exploration Vehicle design requirements, the crewmember adapted to the microgravity state may need to egress the vehicle within a few minutes for safety and operational reasons in various sea state conditions following a water landing. The act of emergency egress includes and is not limited to rapid motor control tasks (including both fine motor such as object manipulation and gross motor such as opening a hatch) and visual acuity tasks while maintaining spatial orientation and postural stability in time to escape safely. Exposure to even low frequency motions (0.2-2.0 Hz) induced by sea conditions surrounding a vessel can cause significant fine and gross motor control problems affecting critical functions. These motion frequencies coupled with the varying sea state conditions (frequencies ranging from 0.125-0.5 Hz) cause performance deficits by affecting the efficacy of motor and visual acuity dependent skills in tasks critical to emergency egress activities such as visual monitoring of displays, actuating discrete controls, operating auxiliary equipment and communicating with Mission Control and recovery teams. Thus, during exploration class missions the sensorimotor disturbances due to the crewmember's adaptation to microgravity may lead to disruption in the ability to maintain postural stability and perform functional egress tasks during the initial introduction to the Earth's gravitational environment. At present, the functional implication of the interactions between a debilitated crewmember during readaptation to Earth s gravity and the environmental constraints imposed by a water landing scenario is not defined and no operational countermeasure has been implemented to mitigate this risk. Stochastic resonance (SR) is a mechanism whereby noise can assist and hence enhance the response of neural systems to relevant, subthreshold sensory signals. Application of subthreshold stochastic resonance noise coupled to sensory input either through the proprioceptive, visual or vestibular sensory systems, has been shown to improve motor function. Crew members who have adapted to microgravity have acquired new sensorimotor strategies that take time to discard. We hypothesize that detection of time-critical subthreshold sensory signals will play a crucial role in improving strategic responses and thus the rate of skill re-acquisition will be faster, leading to faster recovery of function during their re-adaptation to Earth G. Therefore, we expect the use of stochastic resonance mechanisms will enhance the acquisition of new strategic abilities. This process should ensure rapid restoration of functional egress capabilities during the initial return to Earth G after prolonged space flight. Therefore, the overall goals of this project are to investigate performance of motor and visual tasks during varying sea state conditions and develop a countermeasure based on stochastic resonance that could be implemented to enhance sensorimotor capabilities with the aim of facilitating rapid adaptation to Earth s gravity, allowing rapid CEV egress on water in varying sea states following long-duration space flight.

Mulavara, Ajitkumar↗

Neurovestibular Effects of Long-Duration Spaceflight: A Summary of Mir-Phase 1 Experiences

Space motion sickness and associated neurovestibular dysfunction though not completely understood - have been relatively well clinically and operationally characterized on short-duration (1-2 week) Space Shuttle missions (Oman, et al, 1984, 1986; Thornton, et al, 1987; Reschke, et al, 1994). Between March 1995 and June 1998, seven NASA astronauts flew on the Russian Mir space station, as "Phase 1" of the joint effort to build the International Space Station, and provided NASA with invaluable experience on the operational and biomedical problems associated with flights of up to six months in duration. The goal of this paper is to provide a summary of the available information on neurovestibular dysfunction, space motion sickness, and readaptation to Earth's gravity on the NASA Mir flights, based on a set of medical questionnaire data, transcripts, and interviews which are available from the NASA-Mir Phase I program. Records were incomplete and anecdotal. All references to specific crewmembers have been removed, to respect their individual privacy. Material was excerpted from multiple sources of information relating to neurologic function, sensory illusions and motion sickness of NASA-Mir Phase I Program crewmembers. Data were compiled by epoch (in-flight vs landing/postflight) and grouped by neurovestibular topic. The information was recorded either contemporaneously during or within days after landing, or retrospectively weeks to months later. Space motion sickness symptoms are more intense and longer in duration. Sense of spatial orientation takes at least a month to become "natural and instinctive" in space station structures, but mental survey knowledge is apparently not completely developed even after 3 months in some cases. Visual reorientation illusions (VRI) are more easily induced after long exposure to weightlessness. Head movements can cause illusory spinning sensations for up to 7 days postflight. Postural and balance control does not fully recover for at least a month postflight.

Richards, Jason T.↗

Physiological adaptations and countermeasures associated with long-duration spaceflights

Since 1961, there have been more than 165 flights involving several hundred individuals who have remained in a space environment from 15 min to more than a year. In addition, plans exist for humans to explore, colonize, and remain in microgravity for 1000 d or more. This symposium will address the current state of knowledge in select aspects associated with the cardiovascular, fluid and electrolytes, musculoskeletal, and the neuroendocrine and immune systems. The authors will focus on responses, mechanisms, and the appropriate countermeasures to minimize or prevent the physiological and biochemical consequences of a microgravity environment. Since exercise is frequently cited as a generic countermeasure, this topic will be covered in greater detail. Models for simulated microgravity conditions will be discussed in subsequent manuscripts, as will future directions for ground-based research.

NASA Center ARC↗

Reliability and Validity of Ultrasound Cross Sectional Area Measurements for Long-Duration Spaceflight

Limb muscle atrophy and the accompanying decline in function can adversely affect the performance of astronauts during mission-related activities and upon re-ambulation in a gravitational environment. Previous characterization of space flight-induced muscle atrophy has been performed using pre and post flight magnetic resonance imaging (MRI). In addition to being costly and time consuming, MRI is an impractical methodology for assessing in-flight changes in muscle size. Given the mobility of ultrasound (US) equipment, it may be more feasible to evaluate changes in muscle size using this technique. PURPOSE: To examine the reliability and validity of using a customized template to acquire panoramic ultrasound (US) images for determining quadriceps and gastrocnemius anatomical cross sectional area (CSA). METHODS: Vastus lateralis (VL), rectus femoris (RF), medial gastrocnemius (MG), and lateral gastrocnemius (LG) CSA were assessed in 10 healthy individuals (36+/-2 yrs) using US and MRI. Panoramic US images were acquired by 2 sonographers using a customized template placed on the thigh and calf and analyzed by the same 2 sonographers (CX50 Philips). MRI images of the leg were acquired while subjects were supine in a 1.5T scanner (Signa Horizon LX, General Electric) and were analyzed by 3 trained investigators. The average of the 2 US and 3 MRI values were used for validity analysis. RESULTS: High inter-experimenter reliability was found for both the US template and MRI analysis as coefficients of variation across muscles ranged from 2.4 to 4.1% and 2.8 to 3.8%, respectively. Significant correlations were found between US and MRI CSA measures (VL, r = 0.85; RF, r = 0.60; MG, r = 0.86; LG, r = 0.73; p < 0.05). Furthermore, the standard error of measurement between US and MRI ranged from 0.91 to 2.09 sq cm with high limits of agreement analyzed by Bland-Altman plots. However, there were significant differences between absolute values of MRI and US for all muscles. CONCLUSION: The present results indicate that utilizing a customized US template provides reliable measures of leg muscle CSA, and thus could be used to characterize changes in muscle CSA both in flight and on the ground.

Scott, Jessica M.↗

Immune System Dysregulation and Herpesvirus Reactivation Persist During Long-Duration Spaceflight

Background: Immunity, latent herpesvirus reactivation, physiological stress and circadian rhythms were assessed during six month spaceflight onboard ISS. Blood and saliva samples were collected early, mid and late in-flight and returned for immediate analysis. Mid-point study data (10 of 17 planned subjects) will be presented. Results: Some shifts in leukocyte distribution occurred during flight, including alterations in CD8+ T cell maturation. General T cell function was consistently reduced early in-flight. Levels CD8+/IFNg+ producing T cells were depressed early in-flight, and immediately upon landing. Persistent mitogen-dependant reductions were observed in IFNg, IL-17a, IL-10, TNFa and IL-6 production. Monocyte production of IL-10 was reduced, whereas IL-8 levels were increased. Levels of mRNA for the TNFa, IL-6 and IFNg were transiently elevated early in-flight, and the dynamics of TNF and IL-6 gene expression were somewhat antagonistic to their corresponding receptors during flight. The number of virus-specific CD8+ T-cells was measured using MHC tetramers, while their function was measured using intracellular cytokine analysis following peptide stimulation. Both the number and function of EBV-specific cells decreased during flight as compared to preflight levels. The number of CMV-specific T-cells generally increased as the mission progressed while their function was variable. Viral (EBV) load in blood was elevated postflight. Anti-EBV VCA antibodies were significantly elevated by R+0; anti-EA antibodies were not significantly elevated at landing; and anti-CMV antibodies were somewhat elevated during flight. Higher levels of salivary EBV DNA were found during flight. VZV DNA reactivation occurred in ~50 % of astronauts during flight, continuing for up to 30 days post-flight. CMV was shed in 35 % the in-flight and 30% of postflight urine samples of the crewmembers. There was generally a higher level of cortisol as measured in urine and saliva in the astronauts during flight, but plasma cortisol was relatively unchanged during flight. Circadian rhythm of salivary cortisol was altered during flight. Conclusion. Some alterations in immunity do not resolve during six month spaceflight, consequentially resulting in persistent herpesvirus reactivation. Ongoing immune dysregulation may represent specific clinical risks for exploration-class space missions.

Crucian, B. E.↗

Plasma Cytokine Levels During Long-Duration Spaceflight

Determine the in-flight status of immunity, physiological stress, viral immunity/reactivation. Specific measurements include leukocyte distribution, T cell function, cytokine production profiles (mRNA, intracellular, secreted, plasma), virus-specific T cell number/function, latent herpesvirus reactivation, stress hormone levels. Determine the clinical risk related to immune dysregulation for exploration class spaceflight, as well as an appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures. Specific Study Objectives: Determine the nutritional status of astronauts before, during, and after spaceflight ensure adequate intake of energy, protein, and vitamins during missions. The Clinical Nutritional Status Assessment measures dietary intake, body composition, protein, bone, iron, mineral, vitamin, and antioxidant status (60 total analytes). Currently, it is a medical requirement for U.S. crewmembers on-board the ISS. The results of data analysis are used both to understand the connections between nutrition and human health during space flight, and to develop effective dietary strategies to reduce adverse health impacts (including bone loss, loss of important vitamins and minerals, and increased genetic damage from radiation).

Crucian, Brian E.↗

Fibroblast Growth Factor 23 in Long-Duration Spaceflight

Many nutritional factors influence bone, from the basics of calcium and vitamin D, to factors which influence bone through acid/base balance, including protein, sodium, and more. Fibroblast growth factor 23 (FGF23) is a recently identified factor, secreted from osteocytes, which is involved in classic (albeit complex) feedback loops controlling phosphorus homeostasis through both vitamin D and parathyroid hormone (PTH) (1, 2). As osteocytes are gravity sensing cells, it is important to determine if there are changes in FGF23 during spaceflight. In extreme cases, such as chronic kidney disease, FGF23 levels are highly elevated. FGF23 imbalances, secondary to dietary influences, may contribute to skeletal demineralization and kidney stone risk during spaceflight.

Bokhari, R.↗

Effects of Long Duration Spaceflight on Venous and Arterial Compliance: Bed Rest

The primary objective was to determine whether a high sodium diet during bed rest induced alterations in vascular compliance and was related to the incidence of VIIP. Ocular structural and functional measures and vascular ultrasound of the head and neck were acquired in bed rest subjects completing 10-14 days in 6deg head-down tilt.

Ribeiro, L. Christine↗