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At least 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
NASA NTRSDate not supplied

Human placenta-derived stromal cells mitigate select immune responses to simulated weightlessness

Space flight presents unique risks to human health. Microgravity and social isolation are important space flight stressors which have vast impact on multiple systems such as the musculoskeletal, immune and central nervous system (CNS). To explore candidate countermeasures against tissue decrements caused by spaceflight, we performed a pilot study with PLacental-eXpanded stromal (PLX) cells. PLX cells secrete factors that modulate the immune system, but do not trigger host immune responses, enabling treatment in subjects that have intact immune systems. These cells had previous success in treating critical limb ischemia and acute radiation syndrome in murine models. In this study, 4-month-old female mice underwent 30 days of hindlimb unloading (HU) in single housing conditions to simulate long-term weightlessness and isolation. HU and normally ambulating controls were administered with PLX cells or sham-injected with Plasmalyte. We hypothesized that administration of PLX cells will mitigate some of the effects caused by prolonged HU. We found that treatment with PLX cells was well tolerated as indicated by body weights, circulating corticosterone levels and immune organ response to injection of the cells. HU led to the expected decreases in soleus muscle weights and bone loss. We did not observe any protective properties of the PLX cells in the musculoskeletal system but found that the cell treatment partially protected from a subset of HU-induced immune and CNS changes. In the hippocampus, protein levels of 9 of 44 cytokines were downregulated by HU. PLX administration mitigated changes in expression of 8 of these cytokines, including IL-2, IL-6 and MCP-1. To our knowledge, this is the first report on the protective effects of PLX-PAD against HU-induced changes in the cytokine milieu of the CNS. Our findings warrant further studies, which includes testing in actual spaceflight.

Microgravity↗
NASA NTRSDate not supplied

Beyond Low-Earth Orbit: Characterizing Immune and microRNA Differentials Following Simulated Deep Spaceflight Conditions in Mice

Spaceflight missions can cause immune system dysfunction in astronauts with little understanding of immune outcomes in deep space. This study assessed immune responses in mice following ground-based, simulated deep spaceflight conditions, compared to data from astronauts on ISS missions. For ground studies, we simulated microgravity using the hindlimb unloaded mouse model alone or in combination with acute simulated galactic cosmic rays or solar particle events irradiation. Immune profiling results revealed unique immune diversity following each experimental condition, suggesting each stressor results in distinct circulating immune responses, with clear consequences for deep spaceflight. Circulating plasma microRNA sequence analysis revealed involvement in immune system dysregulation. Furthermore, a large astronaut cohort showed elevated inflammation during LEO missions, thereby supporting our simulated ground experiments in mice. Herein, circulating immune biomarkers are defined by distinct deep space irradiation types coupled to simulated microgravity and could be targets for future space health initiatives.

deep spaceflight stressors↗
NASA NTRSDate not supplied

Spaceflight Biospecimen Sharing in Support of Science Discovery and Exploration

For decades, NASA and international partners have flown non-human biological experiments in space to understand the effects of spaceflight and address potential biological hazards. Sending organisms into space is a costly endeavor which makes space-flown biological specimens a valuable resource. To enable maximum scientific return, samples not required by the Principal Investigators are harvested and collected mostly by NASA’s Space Biology Biospecimen Sharing Program. These specimens are collected according to well-established SOPs that maintain quality and integrity. The specimens are then preserved, archived, and made available to the international scientific community through NASA’s Institutional Scientific Collection (ISC) at Ames Research Center (ARC). The ISC-ARC biospecimens and descriptive metadata are findable and accessible for request through the Life Sciences Data Archive (LSDA). The NASA ISC-ARC currently stores over 32,000 specimens from Shuttle, International Space Station, and ground-based investigations (spaceflight analog experiments involving either hindlimb unloading, centrifugation, or partial weight-bearing study designs). Tissues are predominantly from mice and rats, though samples are also available from bacteria and quail. The specimens include tissues from many physiological systems including musculoskeletal, neurosensory, reproductive, respiratory, circulatory, and digestive. Tissues are stored at -80°C, -20°C, +4°C, or ambient and preserved in various fixatives. Descriptive metadata is available for all samples. Historically, these tissues have been used for a wide range of analyses, including histology, genomics, and transcriptomics. Plans are underway to expand the ISC-ARC beyond the mostly-rodent contents, to include a space-relevant microbial culture collection including bacteria, fungi, and yeast. This expansion of the ISC-ARC will now involve identifying and standardizing best practices for microbial curations. To ensure safe long-term storage of microbial isolates, a microbiology laboratory will be dedicated for identification, cell culture, and lyophilization. Awarding of tissue to public science investigators has resulted in 33 publications since 2011, with 48 requests being submitted since 2016. Of note, NASA GeneLab has been awarded ISC-ARC biospecimens in the past few years. GeneLab processes the biospecimens to generate various levels of ‘omics’ data, which are published on GeneLab’s open access online platform for bioinformatics analysis and visualization. This has helped a systems biology community grow around the processed-biospecimens’ datasets, resulting in many new publications and insights. Websites: https://www.nasa.gov/ames/research/space-biosciences/isc-bsp ; https://lsda.jsc.nasa.gov/Biospecimen

Ryan T. Scott↗
NASA NTRSDate not supplied

Sex differences and deep space stressors: effects of 5-ion gcrsim, simulated microgravityand social isolation on immune function, brain, and behavior in mice

This project is testing the hypothesis that Ionizing Radiation (IR), microgravity and social isolation combine synergistically to trigger an oxidative stress response that alters immune homeostasis, brain structure/function, and neurobehavioral/cognitive performance. Specific Aims for this project are to: (1) Determine dose-response curves for acute ‘Five-Ion GCR Simulation’ exposure for immune, brain and performance responses in crew age-matched adult male and female mice; (2) Determine effects of acute ‘Five-Ion GCR Simulation’ exposure singly and in combination with simulated microgravity and social isolation, on immune, brain and performance responses in crew age-matched male and female mice mimicking deep space missions; and (3) Determine efficacy of the dietary antioxidant, Nicotinamide Mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis. Here we report findings from our studies of mature (24-week-old) male and female mice exposed to simulated 5-Ion GCRsim (0, 5, 15, or 50cGy) at the NASA Space Radiation Laboratory (NSRL) followed by combinatorial exposures to 15cGy, simulated microgravity via head-down tilt (hindlimb unloading) and social isolation. Immune, brain and behavioral (sensorimotor, risk-taking & 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 Mars. This project addresses NASA’s efforts to characterize risks and identify appropriate countermeasures in both women and men in anticipation of future deep space missions. Ensuring crew health and performance during extended transits necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes. Supported by the NASA Human Research Program (HRP) Human Factors Behavioral Performance Element Grant 18 18FLAG 2 0028.

behavioral sciences↗
NASA NTRS2021

Overexpression of Catalase in Mitochondria Mitigates Changes in Hippocampal Cytokine Expression Following Simulated Microgravity and Isolation

Isolation on Earth can alter physiology and signaling of organs systems, including the central nervous system. Although not in complete solitude, astronauts operate in an isolated environment during spaceflight. In this study, we determined the effects of isolation and simulated microgravity solely or combined, on the inflammatory cytokine milieu of the hippocampus. Adult female wild-type mice underwent simulated microgravity by hindlimb unloading for 30 days in single or social (paired) housing. In hippocampus, simulated microgravity and isolation each regulate a discrete repertoire of cytokines associated with inflammation. Their combined effects are not additive. A model for mitochondrial reactive oxygen species (ROS) quenching via targeted overexpression of the human catalase gene to the mitochondria (MCAT mice), are protected from isolation- and/or simulated microgravity-induced changes in cytokine expression. These findings suggest a key role for mitochondrial ROS signaling in neuroinflammatory responses to spaceflight and prolonged bedrest, isolation, and confinement on Earth.

simulated microgravity↗
NASA NTRS2023

T-Cell Shenanigans: The Impact of MHC Pathway & Lipid Metabolism Genes on T-Cell Differentiation in the Thymus

Astronaut health and proper immune function are key to the success and sustainability of long term missions in space. While previous studies have observed adaptive immune dysfunction such as diminished WBC counts and cytokine production during spaceflight, the underlying mechanisms behind why immune function worsens are poorly understood. Using transcriptomic data analyzed from mouse thymus tissues available from the GLDS-421 experiment on the Rodent Research-9 mission, we used the GeneLab standardized RNA-Seq pipeline and identified four genes that were largely dysregulated (p<0.05): lipid metabolic genes Hpgd and Pgr and cell cycle regulator genes Cenpe and Kif11. We analyzed how these genes regulate the MHC-TCR interaction, and used this understanding to propose a novel mechanism for alterations to T-cell differentiation. In our experimental methodology, we propose to use 36 transgenic CD4-CD8 mice and 12 wild-type mice from the Jackson Lab to create a microgravity-simulating hindlimb unloading model and test our hypothesis. By silencing the aforementioned genes using custom siRNA based primers, we will use flow cytometry and RNA-Seq to quantify Treg counts in comparison to naive CD4+ cells, Alamar Blue assay for observing the metabolic activity in T-cells, and Enzyme-Linked Immunosorbent Assay (ELISA) to observe the general immune response in terms of T-cell differentiation. We hope this methodology will improve our knowledge of MHC-TCR interaction, contribute to a better understanding of the mechanisms of autoimmune diseases such as lupus, and improve the success rate of newer cancer treatments such as CAR-T cell therapy.

GL4HS↗
NASA NTRS1997

Apoptosis: a mechanism contributing to remodeling of skeletal muscle in response to hindlimb unweighting

The role of apoptosis in the elimination of myonuclei during hindlimb unloading-induced atrophy and the inhibition of apoptosis in the prevention of muscle atrophy were examined. The number of nuclei demonstrating double-stranded DNA fragmentation seen by terminal deoxynucleotidyl transferase (TDT) histochemical staining, an indicator of apoptosis, was significantly increased after 14 days of suspension. Double staining with TDT and antilaminin immunohistochemistry revealed that some TDT-positive nuclei were within the fiber lamina and were most likely myonuclei. The number of fibers containing morphologically abnormal nuclei was also significantly greater in suspended compared with control rats. Combined treatment with growth hormone and insulin-like growth factor I (GH/ IGF-I) and resistance exercise attenuated the increase in TDT-positive nuclei (approximately 26%, P > 0.05) and significantly decreased the number of fibers with morphologically abnormal nuclei. The data suggest that 1) "programmed nuclear death" contributes to the elimination of myonuclei and/or satellite cells from atrophying fibers, and 2) GH/IGF-I administration plus muscle loading ameliorates the apoptosis associated with hindlimb unloading.

Non-NASA Center↗
NASA NTRS1999

The Effect of Skeletal Unloading on Bone Formation: Role of IGF-I

The best documented change in bone during space flight is the near cessation of bone formation. Space flight leads to a decrease in osteoblast number and activity, likely the result of altered differentiation of osteoblast precursors. The net result of these space flight induced changes is weaker bone. To understand the mechanism for these changes poses a challenge. Space flight studies must overcome enormous technical problems, and are necessarily limited in size and frequency. Therefore, ground based models have been developed to evaluate the effects of skeletal unloading. The hindlimb elevation (tail suspension) model simulates space flight better than other models because it reproduces the fluid shifts seen in space travel, is reversible, and is well tolerated by the animals with minimal evidence of stress as indicated by continued weight gain and normal levels and circadian rhythms of corticosterone. This is the model we have used for our experiments. Skeletal unloading by the hindlimb elevation method simulates a number of features of space flight in that bone formation, mineralization, and maturation are inhibited, osteoblast number is decreased, serum and skeletal osteocalcin levels fall, the ash content of bone decreases, and bone strength diminishes. We and others have shown that when osteoblasts or osteoprogenitor cells from the bones of the unloaded limbs are cultured in vitro they proliferate and differentiate more slowly, suggesting that skeletal unloading causes a persistent change in cell function which can be assessed in vitro. In contrast to the unweighted bones of the hindlimbs, no significant change in bone mass or bone formation is observed in the humeri, mandible, and cervical vertebrae during hindlimb elevation. The lack of effect of hindlimb elevation on bones like the humeri, mandible, and cervical vertebrae which are not unloaded by this procedure suggests that local factors rather than systemic effects dominate the response of bone to skeletal unloading. We have focussed on the role of IGF- 1 as the local factor mediating the effects of skeletal unloading on bone formation. IGF-I is produced by bone cells and chondrocytes; these cells have receptors for IGF-I, and respond to IGF-I with an increase in proliferation and function (e.g. collagen, and glycosaminoglycan production, respectively). IGF-I production by bone is under hormonal control, principally by GH and PTH, and IGF-I is thought to mediate some if not all of the effects of GH and PTH on bone growth. Thus, systemic changes in hormones such as GH and PTH may still have effects which vary from bone to bone depending on the loading history.

Bikle, D. D.↗
NASA NTRS2005

The effect of purified compared with nonpurified diet on bone changes induced by hindlimb suspension of female rats

The purpose of this study was to compare the bone changes induced by unloading in rats fed different diets, because space flight studies use a semipurified diet, whereas space flight simulation studies typically use nonpurified diets. Female Sprague-Dawley rats were fed a purified American Institute of Nutrition (AIN) 93G diet or a standard nonpurified diet and kept ambulatory or subjected to unloading by hindlimb suspension (HLS) for 38 days. Bone mineral content (BMC), mechanical strength, and factors related to the diet that affect bone (i.e., urinary calcium excretion, estradiol, and corticosterone) were measured. Average food intakes (grams per day) differed for diets, but caloric intake (kilocalories per day) and the final body masses of treatment groups were similar. The HLS-induced decrease in femoral BMC was not statistically different for rats fed a nonpurified diet (-8.6%) compared with a purified AIN-93G diet (-11.4%). The HLS-induced decrease in femoral mechanical strength was not statistically different for rats fed a nonpurified diet (-24%) compared with a purified AIN-93G diet (-31%). However, bone lengths were decreased (P < 0.05) in rats fed a nonpurified diet compared with a purified diet. Plasma estradiol levels were lower (P < 0.05) in the HLS/AIN-93G group but similar in the HLS and ambulatory rats fed a nonpurified diet. Plasma estradiol was related to femoral BMC (r = 0.85, P < 0.01). Urinary calcium excretion was higher (P < 0.05) in rats fed a nonpurified diet than those fed a purified AIN-93G diet, which is consistent with the higher level of calcium in the nonpurified diet. Urinary corticosterone levels were higher (P < 0.05) in rats fed a nonpurified diet than rats fed the AIN-93G diet. Although the osteopenia induced by unloading was similar in both diet groups, there were differences in longitudinal bone growth, calcium excretion, plasma estradiol levels, and urinary corticosterone levels. Results indicate that the type of standard diet used is an important factor to consider when measuring bone end points.

Bone and Bones/pathology↗
NASA NTRS1999

Five myofibrillar lesion types in eccentrically challenged, unloaded rat adductor longus muscle--a test model

Sarcomere disruptions are observed in the adductor longus (AL) muscles following voluntary reloading of spaceflown and hindlimb suspension unloaded (HSU) rat, which resemble lesions in eccentrically challenged muscle. We devised and tested an eccentric contraction (ECCON) test system for the 14-day HSU rat AL. Six to 7 hours following ECCON, ALs were fixed to allow immunostaining and electron microscopy (EM). Toluidine blue-stained histology semithin sections were screened for lesion density (#/mm2). Serial semithin sections from the ECCON group were characterized for myosin immunointensity of lesions. Five myofibrillar lesion types were identified in histological semithin sections: focal contractions; wide A-bands; opaque areas; missing A-bands; and hyperstretched sarcomeres. Lesion density by type was greater for ECCON than NonECCON ALs (P< or =0.05; focal contractions and opaque regions). Lesion density (#-of-all-five-types/mm2) was significantly different (ECCON: 23.91+/-10.58 vs. NonECCON: 5.48+/-1.28, P< or =0.05; ECCON vs. SHAM: 0.00+/-0.00; P< or = 0.025). PostECCON optimal tension decreased (Poi-drop, 17.84+/-4.22%) and was correlated to lesion density (R2=0.596), but prestretch tension demonstrated the highest correlation with lesion density (R2=0.994). In lesions, the darkly staining A-band lost the normally organized thick filament alignment to differing degrees across the different lesion types. Ranking the five lesion types by a measure of lesion length deformation (hypercontracted to hyperstretched) at the light microscopy level, related to the severity of thick filament registry loss across the lesion types at the electron microscopic level. This ranking suggested that the five lesion types seen in semithin sections at the light level represented a lesion progression sequence and paralleled myosin immunostaining loss as the distorted A-band filaments spread across the hyperlengthening lesion types. Lesion ultrastructure indicated damage involved calcium homeostasis loss (focal contraction lesions) and "thick-filament-centering" failure of titin (wide A-band lesions) in the early stages of lesion development.

NASA Discipline Musculoskeletal↗
NASA NTRS1994

A metabolic cage for the hindlimb suspended rat

Hindlimb suspension has been successfully used to simulate the effects of microgravity in rats. The cage and suspension system developed by E. R. Holton is designed to produce a headward shift of fluid and unload the hindlimbs in rodents, causing changes in bone and muscle similar to those in animals and humans exposed to spaceflight. While the Holton suspension system simulates many of the conditions observed in the spaceflight animal, it does not provide for the collection of urine and feces needed to monitor some metabolic activities. As a result, only limited information has been gathered on the nutritional status, and the gastrointestinal and renal function of animals using that model. Although commercial metabolic cages are available, they are usually cylindrical and require a centrally located suspension system and thus, do not readily permit movement of the rats. The limited floor space of commercial cages may affect comparisons with studies using the Holton model which has more than twice the living space of most commercially available cages. To take advantage of the extra living space and extensive data base that has been developed with the Holton model, Holton's cage was modified to make urine and fecal collections possible.

Evans, J.↗
NASA NTRS1994

Development of a Metabolic Cage for Simulation of Weightlessness in a Laboratory Environment

Astronauts experience many physiological changes during spaceflight and exposure to microgravity. There is a headwardshift of fluids, muscles atrophy, and changes occur in the body's bone structure and hormone levels. This paper describes a unique metabolic cage that was developed to evaluate ground simulation of these effects. Hindlimb or tail suspension in rats has been studied as a model to create the effects of microgravity in order to study how to counteract them. This suspension model, developed by Holton, accurately simulates the effects of weightlessness during spaceflight by unloading the hindlimbs and producing a head-ward shift of fluids. However, obtaining quantitative data on the nutritional state, the gastrointestinal and renal function of these animals has not been possible, until now. Using Holton's tail suspension model, the new metabolic suspension cage effectively separates urine and feces samples for analysis allowing investigators to examine the effects of microgravity in many complex body systems. A description of the cage system, its design, and results of its use is provided along with pictures and details for replication of the cages.

Mulenburg, Gerald M.↗
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 NTRS1999

Macrophage invasion does not contribute to muscle membrane injury during inflammation

Previous observations have shown that neutrophil invasion precedes macrophage invasion during muscle inflammation and that peak muscle injury is observed at the peak of ED1+ macrophage invasion. We tested the hypothesis that neutrophil invasion causes subsequent invasion by ED1+ macrophages and that ED1+ macrophages then contribute significantly to muscle membrane injury during modified muscle use. Rat hindlimbs were unloaded for 10 days followed by reloading by normal ambulation to induce inflammation. Membrane injury was measured by assaying Evans blue-bound serum protein influx through membrane lesions. Muscle neutrophil populations increased significantly during the first 2 h of reloading but ED1+ macrophages did not increase until 24 h. Neutrophil invasion was uncoupled from subsequent macrophage invasion by reloading rat hindlimbs for 2 h to cause neutrophil invasion, followed by resuspension for hours 2-24. This produced similar increases in neutrophil concentration as measured in muscles continuously reloaded for 24 h without causing an increase in macrophages. However, resuspension did not reduce the extent of muscle damage compared with that occurring in muscles that were reloaded continuously for 24 h. Thus, muscle invasion by neutrophils is not sufficient to cause invasion by ED1+ macrophages. In addition, muscle membrane injury that occurs during reloading is independent of invasion by ED1+ macrophages.

NASA Discipline Musculoskeletal↗
NASA NTRS1995

Effect of excess dietary salt on calcium metabolism and bone mineral in a spaceflight rat model

High levels of salt promote urinary calcium (UCa) loss and have the potential to cause bone mineral deficits if intestinal Ca absorption does not compensate for these losses. To determine the effect of excess dietary salt on the osteopenia that follows skeletal unloading, we used a spaceflight model that unloads the hindlimbs of 200-g rats by tail suspension (S). Rats were studied for 2 wk on diets containing high salt (4 and 8%) and normal calcium (0.45%) and for 4 wk on diets containing 8% salt (HiNa) and 0.2% Ca (LoCa). Final body weights were 9-11% lower in S than in control rats (C) in both experiments, reflecting lower growth rates in S than in C during pair feeding. UCa represented 12% of dietary Ca on HiNA diets and was twofold higher in S than in C transiently during unloading. Net intestinal Ca absorption was consistently 11-18% lower in S than in C. Serum 1,25-dihydroxyvitamin D was unaffected by either LoCa or HiNa diets in S but was increased by LoCa and HiNa diets in C. Despite depressed intestinal Ca absoption in S and a sluggish response of the Ca endocrine system to HiNa diets, UCa loss did not appear to affect the osteopenia induced by unloading. Although any deficit in bone mineral content from HiNa diets may have been too small to detect or the duration of the study too short to manifest, there were clear differences in Ca metabolism from control levels in the response of the spaceflight model to HiNa diets, indicated by depression of intestinal Ca absorption and its regulatory hormone.

Navidi, Meena↗
NASA NTRS1999

Gravity and Skeletal Growth

Two simultaneous experiments were performed using 5-week-old male Sprague Dawley rats; in one study, the rats were flown in low earth orbit; in the other study, the hindlimbs of the growing rats were elevated to prevent weight bearing. Following 9 d of unloading, weight bearing was restored for 4, 28, and 76 hrs. Afterwards, additional hindlimb unloading experiments were performed to evaluate the skeletal response to 0, 2, 4, 6, 8, 10, 12, 16, and 24 hrs of restored weight bearing following 7 d of unloading. Cancellous and cortical bone histomorphometry were evaluated in the left tibia at the proximal metaphysis and in the left femur at mid-diaphysis, respectively. Steady-state mRNA levels for bone matrix proteins and skeletal signaling peptides were determined in total cellular RNA extracted from trabeculae from the right proximal tibiametaphysis and periosteum from the right femur. Spaceflight and hindlimb unloading each resulted in cancellous osteopenia, as well as a tendency towards decreased periosteal bone formation. Both models for skeletal unloading resulted in site specific reductions in mRNA levels for transforming growth factor-beta (sub 1) (TGF-beta) osteocalcin (OC), and prepro-alpha (I) subunit of type 1 collagen (collagen) and little or no changes in mRNA levels for glyceraldehyde-3-phosphate dehydrogenase (GAP) and insulin-like growth factor I (IGF-I). Restoration of normal weight bearing resulted in transient increases in mRNA levels for the bone matrix proteins and TGF-beta in the proximal metaphysis and periosteum and no changes in either GAP or IGF-I mRNA levels. The timecourse for the response differed between the two skeletal compartments; the tibial metaphysis responded much more quickly to reloading. These results suggest that the skeletal adaptation to acute physiological changes in mechanical usage are mediated, in part, by changes in mRNA levels for bone matrix proteins and TGF-beta.

Morey-Holton, Emily↗
NASA NTRS2004

Load-dependent regulation of neuromuscular system

Roles of gravitational loading, sarcomere length, and/or tension development on the electromyogram (EMG) of soleus and afferent neurogram recorded at the L5 segmental level of spinal cord were investigated during parabolic flight of a jet airplane or hindlimb suspension in conscious rats. Both EMG and neurogram levels were increased when the gravity levels were elevated from 1-G to 2-G during the parabolic flight. They were decreased when the hindlimbs were unloaded by exposure to actual microgravity or by suspension. These phenomena were related to passive shortening of muscle fibers and/or sarcomeres. Unloading-related decrease in sarcomere length was greater at the central rather than the proximal and distal regions of fibers. These activities and tension development were not detected when the mean sarcomere length was less than 2.03 micrometers. It is suggested that load-dependent regulation of neuromuscular system is related to the tension development which is influenced by sarcomere length.

short duration↗
NASA NTRSDate not supplied

Plasma and Brain Cytokine Responses to Single and Combinatorial Spaceflight Stressors in Male and Female Mice

Spaceflight involves exposure to multiple environmental stressors, including Ionizing Radiation (IR), microgravity, and social isolation. We hypothesize that spaceflight stressors combine synergistically to trigger an oxidative stress response that, in turn, alters immune homeostasis, brain structure/function, and neurobehavioral/cognitive performance. Here, we report plasma and brain cytokine findings from two studies of crew age-matched (24-week-old) male and female mice exposed to simulated 5-Ion GCRsim at the NASA Space Radiation Laboratory (NSRL). In Study 1, mice were exposed to 0, 5, 15, or 50cGy 5-ion GCRsim. Immune and brain measures were acquired either at ‘Acute’ (within 3 days post-irradiation; IR), ‘Intermediate’ (IR+14 days) or ‘Delayed’ (IR+125 days) timepoints. In Study 2, mice were exposed singly and in combination to 15cGy 5-ion GCRsim, simulated microgravity via continuous head-down tilt/hindlimb unloading (HU), and social isolation. Plasma and brain cytokine cytokine profiling revealed sex-specific as well as sex-common responses. Notably, plasma granulocyte colony stimulating factor (GCSF) levels showed significant regulation compared to a single stressor alone, suggesting a potential biomarker responder. Increased GCSF was correlated with corresponding increased blood neutrophil populations. Futhermore, our study provides evidence for robust effects of HU relative to IR alone. This project addresses NASA’s efforts to characterize risks in both women and men in anticipation of future space missions beyond low earth orbit (BLEO). Ensuring crew health and performance during extended transits to the moon and beyond necessitates that sensorimotor and cognitive abilities remain strong to avoid potentially catastrophic health and safety outcomes.

mouse radiation hindlimb unloading spaceflight↗