Long-duration Spaceflight Research Articles

Macro- and microstructural changes in cosmonauts' brains after long-duration spaceflight.

Long-duration spaceflight causes widespread physiological changes, although its effect on brain structure remains poorly understood. In this work, we acquired diffusion magnetic resonance imaging to investigate alterations of white matter (WM), gray matter (GM), and cerebrospinal fluid (CSF) compositions in each voxel, before, shortly after, and 7 months after long-duration spaceflight. We found increased WM in the cerebellum after spaceflight, providing the first clear evidence of sensorimotor neuroplasticity. At the region of interest level, this increase persisted 7 months after return to Earth. We also observe a widespread redistribution of CSF, with concomitant changes in the voxel fractions of adjacent GM. We show that these GM changes are the result of morphological changes rather than net tissue loss, which remained unclear from previous studies. Our study provides evidence of spaceflight-induced neuroplasticity to adapt motor strategies in space and evidence of fluid shift-induced mechanical changes in the brain.

Persistent Globe Flattening in Astronauts following Long-Duration Spaceflight

ABSTRACT Posterior globe flattening has been well-documented in astronauts both during and after long-duration space flight (LDSF) and has been observed as early as 10 days into a mission on the International Space Station. Globe flattening (GF) is thought to be caused by the disc centred anterior forces created by elevated volume and/or pressure within the optic nerve sheath (ONS). This might be the result of increased intracranial pressure, increased intraorbital ONS pressure from compartmentalisation or a combination of these mechanisms. We report posterior GF in three astronauts that has persisted for 7 years or more following their return from LDSFs suggesting that permanent scleral remodelling may have occurred.

High intensity training during spaceflight: results from the NASA Sprint Study

Historically, International Space Station (ISS) exercise countermeasures have not fully protected astronauts’ musculoskeletal and cardiorespiratory fitness. Although these losses have been reduced on more recent missions, decreasing the time required to perform in-flight exercise would permit reallocation of that time to other tasks. To evaluate the effectiveness of a new training prescription, ISS crewmembers performed either the high intensity/lower volume integrated Sprint resistance (3 d wk−1) and aerobic (interval and continuous workouts, each 3 d wk−1 in alternating fashion) exercise program (n = 9: 8M/1F, 48 ± 7 y, 178 ± 5 cm, 77.7 ± 12.0 kg) or the standard ISS countermeasure consisting of daily resistance and aerobic exercise (n = 17: 14M/3F, 46 ± 6 y, 176 ± 6 cm, 80.6 ± 10.5 kg) during long-duration spaceflight. Bone mineral density (dual energy X-ray absorptiometry (DXA)), muscle strength (isokinetic dynamometry), muscle function (cone agility test), and cardiorespiratory fitness (VO2peak) were assessed pre- and postflight. Mixed-effects modeling was used to analyze dependent measures with alpha set at P < 0.05. After spaceflight, femoral neck bone mineral density (−1.7%), knee extensor peak torque (−5.8%), cone agility test time (+7.4%), and VO2peak (−6.1%) were decreased in both groups (simple main effects of time, all P < 0.05) with a few group × time interaction effects detected for which Sprint experienced either attenuated or no loss compared to control. Although physiologic outcomes were not appreciably different between the two exercise programs, to conserve time and optimally prepare crewmembers for the performance of physically demanding mission tasks, high intensity/lower volume training should be an indispensable component of spaceflight exercise countermeasure prescriptions.

Promoting Tech Transfer Between Space and Global Mental Health.

INTRODUCTION: Numerous issues in mental health benefit from technological innovation. An example involves the mental health challenges of long-duration spaceflight (such as a Mars mission), including prolonged confinement, microgravity, and different sunlight exposure lengths. Persisting on Earth are global mental health challenges stemming from disease burdens, limited interview-based diagnostic systems, trial-and-error treatment approaches, and suboptimal access. There is potential for cross-pollinating solutions between these seemingly disparate challenges using a range of emerging technologies such as sensors, omics, and big data. In this review, we highlight the bidirectional value of mental health technology transfer aimed to address issues both on Earth and in space.METHODS: We prepared a systematic review of studies pertaining to mental health technological innovation and space medicine.RESULTS: For Earth mental health technologies translatable to long-duration space missions, we cite several example technologies, including device-based psychotherapy and social support, conversational agents aka chatbots, and nutritional and physical activity focused mental health. Space technologies translatable to Earth mental health include remote sensing devices, global navigation satellite systems, satellite communications, chronotherapies, and nutritional advances.DISCUSSION: There is a rich history of space technologies informing Earth technological trends, including general health care on Earth, and vice versa. To avoid the traditional happenstance approach that results in delays, missed opportunities, and increased cost, and to improve outcomes for both Earth and space utilization of these technologies, we propose increased dialogue and training opportunities to enhance innovation and outcomes.Chang DD, Storch EA, Black L, Berk M, Pellis N, Lavretsky H, Sutton J, Ternes K, Shepanek M, Smith E, Abbott R, Eyre HA. Promoting tech transfer between space and global mental health. Aerosp Med Hum Perform. 2020; 91(9):737745.

The Mobile Lower Body Negative Pressure Gravity Suit for Long-Duration Spaceflight.

Spaceflight Associated Neuro-ocular Syndrome, bone decalcification, and muscle atrophy are among the most prevalent risks associated with long-duration spaceflight. Implementing the lower body negative pressure (LBNP) method is a potential countermeasure for these risks. LBNP counteracts head-ward fluid shifts and generates ground-reaction forces (GRFs). GRFs are beneficial for maintaining bones and muscles by producing gravity-like loads experienced on Earth. Currently, LBNP devices are large/bulky, and usually require the subject to maintain a stationary position. However, our new mobile gravity suit is relatively small, untethered, and flexible in order to improve mobility in space. We hypothesized that this novel mobile gravity suit generates greater GRFs than a standard LBNP chamber. While lying supine, GRF data were recorded in both devices using foot sole sensors and a weight scale. At -40 mmHg, the gravity suit generated a mean maximum bodyweight of 125 ± 22% (P < 0.02) whereas the standard LBNP chamber generated 91 ± 24%. The standard LBNP chamber generated a single force on the stationary subject, which was expressed as AW(LBNP) = GRF, where Aw = cross-sectional area (CSA) of subject’s waist. However, the mobile gravity suit generated an additional force based on the following equation, (AF + AW)LBNP = GRF, where AF = CSA of subject’s feet. The additional force was further expressed as F1 + F2 = AF × LBNP, where F1 = spinal loading force, F2 = waist shear force, and AF × LBNP = the total downward foot force. Thus, the mobile gravity suit produces higher percentages of bodyweight due to the suit’s novel design.

Vestibular and Cardiovascular Responses After Long-Duration Spaceflight.

BACKGROUND: The vestibulo-sympathetic reflex operates during orthostatically challenging movements to initiate cardiovascular responses in advance of a baroreceptor-mediated response. The objective of this study was to determine whether there was an association between changes in vestibular function and cardiovascular responses during a prone-to-stand movement in astronauts after return from long-duration spaceflight.METHODS: Thirteen crewmembers who participated in International Space Station missions were tested before spaceflight and 1 d after landing. Vestibular function was evaluated by computerized dynamic posturography while their head was erect and while they performed dynamic head tilts. Heart rate and mean arterial blood pressure were measured while the subjects were in prone and standing positions.RESULTS: The 21.4% increase in the astronauts' heart rate during the prone to stand maneuver after spaceflight correlated significantly with their spaceflight-induced 48.7% decrease in postural stability during dynamic head tilts. The larger mean arterial pressure in the prone position after spaceflight compared to preflight (+7%) also correlated with the postflight decrease in postural stability during dynamic head tilts.CONCLUSION: These results indicate that an appropriate vestibular function is important to evoke optimum vestibulo-sympathetic response during orthostatically challenging voluntary movements performed after spaceflight. They also suggest that there may be a greater need to generate an anticipatory cardiovascular response after spaceflight.Deshpande N, Laurie SS, Lee SMC, Miller CA, Mulavara AP, Peters BT,Reschke MF, Stenger MB, Taylor LC, Wood SJ, Clément GR, Bloomberg JJ. Vestibular and cardiovascular responses after long-duration spaceflight. Aerosp Med Hum Perform. 2020; 91(8):621-627.

Efficacy of Gradient Compression Garments in the Hours After Long-Duration Spaceflight.

The incidence of presyncopal events is high soon after a long-duration spaceflight;>60% of returning astronauts could not complete a 10-min 80° head-up tilt test on landing day (R+0) after ~6 months of spaceflight. The objective of this study was to demonstrate the ability of a lower body gradient compression garment (GCG) to protect against an excessive increase in heart rate and a decrease in blood pressure during standing after long-duration spaceflight. Methods: Eleven astronauts (9 M, 2 F) volunteered to participate. The stand test protocol consisted of 2 min of prone rest followed by 3.5 min of standing. Subjects completed one familiarization session, two preflight data collection sessions in standard clothing, and three tests on landing day while wearing GCG. Postflight tests were conducted 1–4 h (R+0A), ~12 h (R+0B), and ~28 h after landing (R+0C). Results: All astronauts completed the stand test preflight. Three astronauts were unable to attempt the stand test at R+0A, and one of these was unable to start the test at R+0B. One astronaut was unable to complete 3.5 min of standing at R+0B (test ended at 3.3 min). Review of the individual’s blood pressure data revealed no hypotension but the astronaut reported significant motion sickness. Of the astronauts who participated in testing on landing day, the heart rate and mean arterial pressure responses to standing (stand-prone) were not different than preflight at any of the postflight sessions. Conclusion: Wearing the GCG after spaceflight prevented the tachycardia that normally occurs while standing after spaceflight without compression garments and protected against a decrease in blood pressure during a short stand test.

Bioinspired Scaffold Action Under the Extreme Physiological Conditions of Simulated Space Flights: Osteogenesis Enhancing Under Microgravity.

Prolonged exposure to microgravity (MG) during long-duration space flights is known to induce severe dysregulation of osteoblast functions connected to a significant bone loss, similar to the condition induced by osteoporosis. Hence, we here present MG as a promising model to challenge the effectiveness of new scaffolds designed for bone regeneration in counteracting bone loss. To this end, we carried out an integrative study aimed to evaluate, in the extreme condition of Random Positioning Machine-simulated MG, the osteoinductive potential of nanocrystalline magnesium-doped hydroxyapatite/type I collagen composite scaffold (MHA/Coll), that we previously demonstrated to be an excellent tool for bone tissue engineering. Initially, to test the osteoinductive properties of our bioinspired-scaffold, MHA/Coll structure was fully characterized under MG condition and compared to its static counterpart. Human bone marrow-derived mesenchymal stem cells were used to investigate the scaffold biocompatibility and ability to promote osteogenic differentiation after long-duration exposure to MG (up to 21 days). The results demonstrate that the nanostructure of MHA/Coll scaffold can alleviate MG-induced osteoblast dysfunction, promoting cell differentiation along the osteogenic lineage, with a consequent reduction in the expression of the surface markers CD29, CD44, and CD90. Moreover, these findings were corroborated by the ability of MHA/Coll to induce the expression of genes linked to osteogenesis, including alkaline phosphatase and osteocalcin. This study confirmed MHA/Coll capabilities in promoting osteogenesis even in extreme long-term condition of MG, suggesting MG as an effective challenging model to apply in future studies to validate the ability of advanced scaffolds to counteract bone loss, facilitating their application in translational Regenerative Medicine and Tissue Engineering.

Biofilms-Impacts on Human Health and Its Relevance to Space Travel.

As the world looks towards the stars, the impacts of endogenous and exogenous microorganisms on human health during long-duration space flight are subjects of increased interest within the space community. The presence and continued growth of bacterial biofilms about spacecraft has been documented for decades; however, the impact on crew health is in its infancy. The impacts of biofilms are well known in the medical, agricultural, commercial, and industrial spaces. It less known that biofilms are undermining many facets of space travel and that their effects need to be understood and addressed for future space missions. Biofilms can damage space crew health and spoil limited food supply. Yet, at the same time, they can benefit plant systems for food growth, nutrient development, and other biological systems that are being explored for use in space travel. Various biofilm removal techniques have been studied to mitigate the hazards posed by biofilm persistence during space travel. Because the presence of biofilms can advance or hinder humanity’s space exploration efforts, an understanding of their impacts over the duration of space flights is of paramount importance.

Gynecologic Risk Mitigation Considerations for Long-Duration Spaceflight.

INTRODUCTION: As NASA and its international partners, as well as the commercial spaceflight industry, prepare for missions of increasing duration and venturing outside of low-Earth orbit, mitigation of medical risk is of high priority. Gynecologic considerations constitute one facet of medical risk for female astronauts. This manuscript will review the preflight, in-flight, and postflight clinical evaluation, management, and prevention considerations for reducing gynecologic and reproductive risks in female astronauts.METHODS: Relevant gynecological articles from databases including Ovid, Medline, Web of Science, various medical libraries, and NASA archives were evaluated for this review. In particular, articles addressing preventive measures or management of conditions in resource-limited environments were evaluated for applicability to future long-duration exploration spaceflight.RESULTS: Topics including abnormal uterine bleeding, anemia, bone mineral density, ovarian cysts, venous thromboembolism, contraception, fertility, and health maintenance were reviewed. Prevention and treatment strategies are discussed with a focus on management options that consider limitations of onboard medical capabilities.DISCUSSION: Long-duration exploration spaceflight will introduce new challenges for maintenance of gynecological and reproductive health. The impact of the space environment outside of low-Earth orbit on gynecological concerns remains unknown, with factors such as increased particle radiation exposure adding complexity and potential risk. While the most effective means of minimizing the impact of gynecologic or reproductive pathology for female astronauts is screening and prevention, gynecological concerns can arise unpredictably as they do on Earth. Careful consideration of gynecological risks and potential adverse events during spaceflight is a critical component to risk analysis and preventive medicine for future exploration missions.Steller JG, Blue RS, Burns R, Bayuse TM, Antonsen EL, Jain V, Blackwell MM, Jennings RT. Gynecologic risk mitigation considerations for long-duration spaceflight. Aerosp Med Hum Perform. 2020; 91(7):543-564.

Gravitational Transitions Increase Blood-brain Barrier Permeability In Humans

Scientific Abstract While spaceflight-associated neuro-ocular syndrome (SANS) related to intracranial hypertension (IH) is considered NASA’s top health risk for long-duration spaceflight, the underlying mechanisms remain unclear. PURPOSE: To examine if repeated bouts of micro- and hypergravity during parabolic flight (PF) would increase blood-brain barrier (BBB) permeability subsequent to the combined effects of cerebral hyper-perfusion (hemodynamic) and systemic oxidative-nitrosative (molecular) stress. METHODS: Six participants (5♂, 1♀) aged 29 ± 11 years were examined before, during and after PF. Six gender and age- matched (27 ± 6 years) controls were subject to the same procedures/experimental timeline with the exception of PF. Duplex ultrasound was employed to measure blood flow in the anterior (internal carotid artery, ICA) and posterior (vertebral artery, VA) circulation, with venous blood assayed for biomarkers specific to oxidative-nitrosative stress (electron paramagnetic resonance spectroscopy/ozone-based chemiluminescence) and structural integrity of the neurovascular unit (NVU, chemiluminescence/ELISA). RESULTS: PF was associated with a selective increase in VA flow during the most marked gravitational transition from micro- to hypergravity (P < 0.05). Increases in oxidative-nitrosative stress, glio-vascular GFAP and S100ß were observed after PF (P > 0.05), the latter proportional to the increase in VA flow, whereas biomarkers of neuronal-axonal damage (neuron-specific enolase, neurofilament light-chain, ubiquitin carboxy-terminal hydrolase L1 and tau) remained stable (P > 0.05). CONCLUSION: Collectively, these data are the first to demonstrate that acute gravitational transitions result in minor BBB disruption due to the combined effects of hemodynamic-molecular stress thereby proposing an alternative candidate mechanism and biomarkers for the reported neurological sequelae underlying SANS.

The Impact of 6 and 12 Months in Space on Human Brain Structure and Intracranial Fluid Shifts.

As plans develop for Mars missions, it is important to understand how long-duration spaceflight impacts brain health. Here we report how 12-month (n = 2 astronauts) versus 6-month (n = 10 astronauts) missions impact brain structure and fluid shifts. We collected MRI scans once before flight and four times after flight. Astronauts served as their own controls; we evaluated pre- to postflight changes and return toward preflight levels across the 4 postflight points. We also provide data to illustrate typical brain changes over 7 years in a reference dataset. Twelve months in space generally resulted in larger changes across multiple brain areas compared with 6-month missions and aging, particularly for fluid shifts. The majority of changes returned to preflight levels by 6 months after flight. Ventricular volume substantially increased for 1 of the 12-month astronauts (left: +25%, right: +23%) and the 6-month astronauts (left: 17 ± 12%, right: 24 ± 6%) and exhibited little recovery at 6 months. Several changes correlated with past flight experience; those with less time between subsequent missions had larger preflight ventricles and smaller ventricular volume increases with flight. This suggests that spaceflight-induced ventricular changes may endure for long periods after flight. These results provide insight into brain changes that occur with long-duration spaceflight and demonstrate the need for closer study of fluid shifts.

Cerebrovascular reactivity: a new frontier for measuring cognitive health in models of accelerated ageing?

Cerebrovascular reactivity: a new frontier for measuring cognitive health in models of accelerated ageing?

Arterial structure and function during and after long-duration spaceflight.

Spaceflight missions expose astronauts to increased risk of oxidative stress and inflammatory damage that might accelerate the development of asymptomatic cardiovascular disease. The purpose of this investigation was to determine whether long-duration spaceflight (>4 mo) results in structural and functional changes in the carotid and brachial arteries. Common carotid artery (CCA) intima-media thickness (cIMT), CCA distensibility and stiffness, and brachial artery endothelium-dependent and -independent vasodilation were measured in 13 astronauts (10 men, 3 women) ~180 and 60 days before launch, during the mission on ~15, 60, and 160 days of spaceflight, and within 1 wk after landing. Biomarkers of oxidative stress and inflammation were measured at corresponding times in fasting blood samples and urine samples from 24- or 48-h pools. Biomarkers of oxidative stress and inflammation increased during spaceflight, but most returned to preflight levels within 1 wk of landing. Mean cIMT, CCA stiffness, and distensibility were not significantly different from preflight at any time. As a group, neither mean endothelium-dependent nor -independent vasodilation changed from preflight to postflight, but changes within individuals in endothelial function related to some biomarkers of oxidative stress. Whereas biomarkers of oxidative stress and inflammation are elevated during spaceflight, CCA and brachial artery structure and function were not changed by spaceflight. It is unclear whether future exploration missions, with an extended duration in altered gravity fields and higher radiation exposure, may be problematic.NEW & NOTEWORTHY Carotid artery structure and stiffness did not change on average in astronauts during long-duration spaceflight (<12 mo), despite increased oxidative stress and inflammation. Most oxidative stress and inflammation biomarkers returned to preflight levels soon after landing. Brachial artery structure and function also were unchanged by spaceflight. In this group of healthy middle-aged male and female astronauts, spaceflight in low Earth orbit does not appear to increase long-term cardiovascular health risk.

Exercise and Testosterone Countermeasures to Mitigate Metabolic Changes during Bed Rest

Background/Objectives: Exercise is a front-line countermeasure used to maintain astronaut health during long-duration spaceflight; however, reductions in metabolic health still occur. Accordingly, we evaluated serial changes in metabolic parameters in a spaceflight analog and evaluated the efficacy of exercise with or without the addition of low-dose testosterone treatment on mitigating adverse metabolic changes. Subjects/Methods: Healthy young (<55 years) men were randomly assigned to one of three groups during 70-days of strict, diet controlled, 6° head-down bed rest: Control (CON, n=9), exercise plus testosterone countermeasure (TEX, n=8), or exercise countermeasure plus placebo (PEX, n=9). Basal metabolic rate (BMR), glucose tolerance, and insulin sensitivity were measured before, during, and after bed rest. Exercise energy expenditure and excess post-exercise oxygen consumption were measured in TEX and PEX subjects during bed rest. Results: Leptin decreased during bed rest (Pre to BR+0 changed from 6.9 ± 5.1, 5.8 ± 4.2, and 4.7 ± 4.1 to 7.9 ±3.6, 6.5 ± 4.6, and 4.1 ±3.0 ug• L−1 for CON, PEX, and TEX respectively). Bed rest induced a decrease in BMR (Pre to BR57 changed from 1655 ± 212, 1629 ± 108, and 1706 ± 146 to 1476 ± 166, 1668 ± 142, and 1603 ± 132 kcal • day−1 ± 95%CI for CON, PEX, and TEX respectively). Similarly, bed rest negatively affected glucose metabolism assessed by 2hr OGTT glucose (Pre to BR66 changed from 6.29 ± 0.72, 5.13 ± 0.72, and 5.87 ± 0.73 to 6.62 ± 0.72, 5.83 ± 0.72, and 7.08 ± 0.72 mmol • L−1 ± 95%CI). Reambulation following bed rest positively affected glucose tolerance in CON (2hr OGTT glucose at BR+12: 5.3 ± 0.72, 6.42 ± 0.73, and 6.04 ± 0.73 mmol • L−1 ± 95%CI). Testosterone protected against bed rest induced insulin resistance (HOMA-IR from Pre to BR+66 changed from 1.74 ± 0.54, 1.18 ± 0.55, and 1.45 ± 0.56 to 2.24 ± 0.56, 1.47 ± 0.54, and 1.07 ± 0.54). Conclusion: This study confirmed that inactivity during 70 days of head-down bed rest adversely affects metabolic health. The daily exercise countermeasures were beneficial but not completely protective of bed rest induced decrements in metabolic health. Supplementary countermeasures such as testosterone may provide additional benefits not provided by exercise alone.

The Nutriss Study: A New Approach to Calibrate Diet and Exercise in Long-Term Space Missions to Maintain Body Fat, Muscle and Fluid Homeostasis

Energy balance maintenance is crucial to preserve astronaut’s wellness and quality of life during long-duration spaceflight and nutritional intervention can effectively counteract the detrimental effect of microgravity on skeletal muscle mass and metabolism. NutrISS (Nutrition monitoring for the International Space Station) is an Italian Space Agency (ASI) biomedical experiment investigating the changes in body composition during long-term spaceflight. The goal of this proof-of-concept study is to monitor the body composition of astronauts and, if needed, to provide nutritional advice during the mission. It has been executed on the ISS, from July 2019 till January 2020 and sponsored by ESA. The payloads selected for the mission “BEYOND” result from a public-call funded and coordinated by ASI, in the frame of its national mission of promoting and fostering the culture of space across the Country and providing access to the ISS as a laboratory in space to the Italian research community. The utilization support services is ensured by Argotec/Telespazio (UTISS Team). An astronaut underwent to baseline data collections, i.e. body composition, anthropometric evaluation and energy and metabolic assessment carried out by the scientific team. Body composition, estimated through resistance/reactance to a low-intensity current has been assessed with a Bio-Impedance Analyser (BIA) device manufactured by Akern and modified by Kayser Italia. To maintain the participant in near-neutral energy balance, the science team monitored monthly the astronaut body mass during the entire space flight period. Advice on energy intake was given to the astronaut when needed.

Isokinetic Force and Work Capacity After Long-Duration Space Station Mir and Short-Term International Space Station Missions.

INTRODUCTION: The effects of long-duration (213.0 ± 30.5 d) stays aboard the orbital station Mir and short-term (∼10 d) spaceflights aboard the International Space Station (ISS) on the joint torques of various muscles and work capacity of knee extensors were studied in male cosmonauts.METHODS: Joint torque and muscle endurance testing was performed 30 d before and 3-5 d after a spaceflight, using a LIDO® Multi-Joint Isokinetic Rehabilitation System (USA).RESULTS: Greater postflight changes in maximal joint torque were observed for back, knee, and ankle extensors compared with flexors, and the difference was especially clearly seen after long-term spaceflights. The decrease in maximal joint torque of hip extensors substantially varied, being the greatest in voluntary concentric movements in a low-velocity high-force mode at angular velocities of 30 and 60° · s-1 (by 16 and 13%, respectively) and the lowest in high-velocity modes at velocities of 120 and 180° · s-1 (by 9 and 11%, respectively). Muscle work capacity was inferred from the gradient of declining muscle force produced in a series of rhythmic voluntary concentric movements and was found to decrease after both short- and long-term spaceflights. The area under the muscle contraction curve decreased to a greater extent and in all regions of the curve after long-term spaceflights. The fatigue index averaged 0.90 ± 0.03 at baseline and remained much the same, 0.90 ± 0.04, after a short-term spaceflight. However, after a long-duration spaceflight, the fatigue index increased 14.1%.DISCUSSION: The finding that the contractile functions and work capacity of muscles decrease more after long-term than after short-term spaceflights in spite of the physical training program of a certain type gave grounds to assume that physical training employed in long-term spaceflights were insufficient to simulate the daily mechanical load that the cosmonauts had before a spaceflight.Koryak YA. Isokinetic force and work capacity after long-duration Space Station Mir and short-term International Space Station missions. Aerosp Med Hum Perform. 2020; 91(5):422-431.

Interactions of natural killer cells and pancreatic cancer cells in simulated microgravity

Abstract One of the major concerns of long-duration spaceflight is the exposure of astronauts to space radiation and the potential for cancer development. Natural killer (NK) cells continuously survey the body for such abnormalities and upon detection are activated to produce pro-inflammatory cytokines as well as cytotoxins which induce apoptosis of the cancer cells. This study employed the rotary cell culture system to generate a simulated microgravity (SMG) environment in order to assess its effect upon the growth of human cancer cells and their susceptibility to lysis by NK cells. We found that SMG diminishes the numbers of both pancreatic cancer cells and NK92MI, a human NK cell line, over a 7 d culture period. Additionally, SMG NK92MI cells had a ~50% decrease in cytotoxicity against PANC-1 pancreatic cancer cells. Surprisingly, a long-term SMG culture of up to 14 d resulted in complete restoration of NK92MI cell cytotoxic function. Interestingly, SMG cultured NK92MI cells produced more IFN-gamma than Static NK cells throughout the time periods assessed. In comparison, 7 d culture of pancreatic cancer cells in SMG led to a ~50% reduction in the ability of either Static or SMG NK92MI cells to induce apoptosis in the SMG cultured cancer cells. Therefore, over a two-week period in SMG culture, NK92MI cells were able to adapt to the environment and recover cytotoxic function, however, pancreatic cancer cells cultured in SMG acquired resistance to lysis by the NK cells. Hence, cancer cells developing in astronauts in microgravity might have a greater potential to resist NK cell control than in patients here on Earth which upon elucidation may aid in the identification of relevant new tumor targets for therapeutics.

Intracranial Effects of Microgravity: A Prospective Longitudinal MRI Study.

Background Astronauts on long-duration spaceflight missions may develop changes in ocular structure and function, which can persist for years after the return to normal gravity. Chronic exposure to elevated intracranial pressure during spaceflight is hypothesized to be a contributing factor, however, the etiologic causes remain unknown. Purpose To investigate the intracranial effects of microgravity by measuring combined changes in intracranial volumetric parameters, pituitary morphologic structure, and aqueductal cerebrospinal fluid (CSF) hydrodynamics relative to spaceflight and to establish a comprehensive model of recovery after return to Earth. Materials and Methods This prospective longitudinal MRI study enrolled astronauts with planned long-duration spaceflight. Measures were conducted before spaceflight followed by 1, 30, 90, 180, and 360 days after landing. Intracranial volumetry and aqueductal CSF hydrodynamics (CSF peak-to-peak velocity amplitude and aqueductal stroke volume) were quantified for each phase. Qualitative and quantitative changes in pre- to postflight (day 1) pituitary morphologic structure were determined. Statistical analysis included separate mixed-effects models per dependent variable with repeated observations over time. Results Eleven astronauts (mean age, 45 years ± 5 [standard deviation]; 10 men) showed increased mean volumes in the brain (28 mL; P < .001), white matter (26 mL; P < .001), mean lateral ventricles (2.2 mL; P < .001), and mean summated brain and CSF (33 mL; P < .001) at postflight day 1 with corresponding increases in mean aqueductal stroke volume (14.6 μL; P = .045) and mean CSF peak-to-peak velocity magnitude (2.2 cm/sec; P = .01). Summated mean brain and CSF volumes remained increased at 360 days after spaceflight (28 mL; P < .001). Qualitatively, six of 11 (55%) astronauts developed or showed exacerbated pituitary dome depression compared with baseline. Average midline pituitary height decreased from 5.9 to 5.3 mm (P < .001). Conclusion Long-duration spaceflight was associated with increased pituitary deformation, augmented aqueductal cerebrospinal fluid (CSF) hydrodynamics, and expansion of summated brain and CSF volumes. Summated brain and CSF volumetric expansion persisted up to 1 year into recovery, suggesting permanent alteration. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Lev in this issue.

Association of Long-Duration Spaceflight With Anterior and Posterior Ocular Structure Changes in Astronauts and Their Recovery

During long-duration spaceflights, nearly all astronauts exhibit some change in ocular structure within the spectrum of spaceflight-associated neuro-ocular syndrome. To quantitatively determine in a prospective study whether changes in ocular structures hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome occur during 6-month missions on board the International Space Station (ISS). The Ocular Health ISS Study of astronauts is a longitudinal prospective cohort study that uses objective quantitative imaging modalities. The present cohort study investigated the ocular structure of 11 astronauts before, during, and after a 6-month mission on board the ISS. Changes in ocular structure (peripapillary edema, axial length, anterior chamber depth, and refraction) hypothesized to be associated with the development of spaceflight-associated neuro-ocular syndrome during 6-month missions on board the ISS were assessed. Statistical analyses were conducted from August 2018 to January 2019. Before launch, the 11 astronauts were a mean (SD) age of 45 (5) years, a mean (SD) height of 1.76 (0.05) m, and a mean (SD) weight of 75.3 (7.1) kg. Six astronauts did not have prior spaceflight experience, 3 had completed short-duration missions on board the Space Shuttle, and 2 had previous long-duration spaceflight missions on board the ISS. Their mean (SD) duration on board the ISS in the present study was 170 (19) days. Optic nerve head rim tissue and peripapillary choroidal thickness increased from preflight values during early spaceflight, with maximal change typically near the end of the mission (mean change in optic nerve head rim tissue thickness on flight day 150: 35.7 μm; 95% CI, 28.5-42.9 μm; P < .001; mean choroidal thickness change on flight day 150: 43 μm; 95% CI, 35-46 μm; P < .001). The mean postflight axial length of the eye decreased by 0.08 mm (95% CI, 0.10-0.07 mm; P < .001) compared with preflight measures, and this change persisted through the last examination (1 year after spaceflight: 0.05 mm; 95% CI, 0.07-0.03 mm; P < .001). This study found that spaceflight-associated peripapillary optic disc edema and choroid thickening were observed bilaterally and occurred in both sexes. In addition, this study documented substantial peripapillary choroid thickening during spaceflight, which has never been reported in a prospective study cohort population and which may be a contributing factor in spaceflight-associated neuro-ocular syndrome. Data collection on spaceflight missions longer than 6 months will help determine whether the duration of the mission is associated with exacerbating these observed changes in ocular structure or visual function.