The effect of prolonged spaceflight on cerebrospinal fluid and perivascular spaces of astronauts and cosmonauts.

Long-duration spaceflight induces changes to the brain and cerebrospinal fluid compartments and visual acuity problems known as spaceflight-associated neuro-ocular syndrome (SANS). The clinical relevance of these changes and whether they equally affect crews of different space agencies remain unknown. We used MRI to analyze the alterations occurring in the perivascular spaces (PVS) in NASA and European Space Agency astronauts and Roscosmos cosmonauts after a 6-mo spaceflight on the International Space Station (ISS). We found increased volume of basal ganglia PVS and white matter PVS (WM-PVS) after spaceflight, which was more prominent in the NASA crew than the Roscosmos crew. Moreover, both crews demonstrated a similar degree of lateral ventricle enlargement and decreased subarachnoid space at the vertex, which was correlated with WM-PVS enlargement. As all crews experienced the same environment aboard the ISS, the differences in WM-PVS enlargement may have been due to, among other factors, differences in the use of countermeasures and high-resistive exercise regimes, which can influence brain fluid redistribution. Moreover, NASA astronauts who developed SANS had greater pre- and postflight WM-PVS volumes than those unaffected. These results provide evidence for a potential link between WM-PVS fluid and SANS.

Six-day dry immersion leads to downregulation of slow-fiber type and mitochondria-related genes expression.

The soleus muscle in humans is responsible for maintaining an upright posture and participating in walking and running. Under muscle disuse, it undergoes molecular signaling changes that result in altered force and work capacity. The triggering mechanisms and pathways of these changes are not yet fully understood. In this article, we aimed to detect the molecular pathways that are involved in the unloading-induced alterations in the human soleus muscle under 6-days of dry immersion. A 6-day dry immersion led to the downregulation of mitochondrial biogenesis and dynamics markers, upregulation of calcium-dependent CaMK II phosphorylation, enhanced PGC1α promoter region methylation, and altered muscle micro-RNA expression, without affecting p-AMPK content or fiber-type transformation.NEW & NOTEWORTHY Dry immersion dysregulates mitochondrial genes expression, affects mi-RNA expression and PGC1 promoter methylation.

Brain ventricular volume changes induced by long-duration spaceflight.

Long-duration spaceflight induces detrimental changes in human physiology. Its residual effects and mechanisms remain unclear. We prospectively investigated the changes in cerebrospinal fluid (CSF) volume of the brain ventricular regions in space crew by means of a region of interest analysis on structural brain scans. Cosmonaut MRI data were investigated preflight (n = 11), postflight (n = 11), and at long-term follow-up 7 mo after landing (n = 7). Post hoc analyses revealed a significant difference between preflight and postflight values for all supratentorial ventricular structures, i.e., lateral ventricle (mean % change ± SE = 13.3 ± 1.9), third ventricle (mean % change ± SE = 10.4 ± 1.1), and the total ventricular volume (mean % change ± SE = 11.6 ± 1.5) (all P < 0.0001), with higher volumes at postflight. At follow-up, these structures did not quite reach baseline levels, with still residual increases in volume for the lateral ventricle (mean % change ± SE = 7.7 ± 1.6; P = 0.0009), the third ventricle (mean % change ± SE = 4.7 ± 1.3; P = 0.0063), and the total ventricular volume (mean % change ± SE = 6.4 ± 1.3; P = 0.0008). This spatiotemporal pattern of CSF compartment enlargement and recovery points to a reduced CSF resorption in microgravity as the underlying cause. Our results warrant more detailed and longer longitudinal follow-up. The clinical impact of our findings on the long-term cosmonauts' health and their relation to ocular changes reported in space travelers requires further prospective studies.

Corrigendum: Impact of different ground-based microgravity models on human sensorimotor system.

[This corrects the article DOI: 10.3389/fphys.2023.1085545.].

Impact of different ground-based microgravity models on human sensorimotor system.

This review includes current and updated information about various ground-based microgravity models and their impact on the human sensorimotor system. All known models of microgravity are imperfect in a simulation of the physiological effects of microgravity but have their advantages and disadvantages. This review points out that understanding the role of gravity in motion control requires consideration of data from different environments and in various contexts. The compiled information can be helpful to researchers to effectively plan experiments using ground-based models of the effects of space flight, depending on the problem posed.

Prolonged microgravity induces reversible and persistent changes on human cerebral connectivity.

The prospect of continued manned space missions warrants an in-depth understanding of how prolonged microgravity affects the human brain. Functional magnetic resonance imaging (fMRI) can pinpoint changes reflecting adaptive neuroplasticity across time. We acquired resting-state fMRI data of cosmonauts before, shortly after, and eight months after spaceflight as a follow-up to assess global connectivity changes over time. Our results show persisting connectivity decreases in posterior cingulate cortex and thalamus and persisting increases in the right angular gyrus. Connectivity in the bilateral insular cortex decreased after spaceflight, which reversed at follow-up. No significant connectivity changes across eight months were found in a matched control group. Overall, we show that altered gravitational environments influence functional connectivity longitudinally in multimodal brain hubs, reflecting adaptations to unfamiliar and conflicting sensory input in microgravity. These results provide insights into brain functional modifications occurring during spaceflight, and their further development when back on Earth.

Application of Space Technologies Aimed at Proprioceptive Correction in Terrestrial Medicine in Russia.

Space technologies greatly contributed not only to space medicine but also to terrestrial medicine, which actively involves these technologies in everyday practice. Based on the existing countermeasures, and due to similarities of sensorimotor alterations provoked by the weightlessness with various neurological disorders, a lot of work has been dedicated to adaptation and introduction of these countermeasures for rehabilitation of patients. Axial loading suit and mechanical stimulation of the soles' support zones are used in mitigation of stroke and traumatic brain injury consequences. They are also applied for rehabilitation of children with cerebral palsy. Complex application of these proprioceptive correction methods in neurorehabilitation programs makes it possible to effectively treat neurological patients with severe motor disturbances and significant brain damage.

Dry immersion induced acute low back pain and its relationship with trunk myofascial viscoelastic changes.

Microgravity induces spinal elongation and Low Back Pain (LBP) but the pathophysiology is unknown. Changes in paraspinal muscle viscoelastic properties may play a role. Dry Immersion (DI) is a ground-based microgravity analogue that induces changes in m. erector spinae superficial myofascial tissue tone within 2 h. This study sought to determine whether bilateral m. erector spinae tone, creep, and stiffness persist beyond 2 h; and if such changes correlate with DI-induced spinal elongation and/or LBP. Ten healthy males lay in the DI bath at the Institute of Biomedical Problems (Moscow, Russia) for 6 h. Bilateral lumbar (L1, L4) and thoracic (T11, T9) trunk myofascial tone, stiffness and creep (MyotonPRO), and subjective LBP (0-10 NRS) were recorded before DI, after 1h, 6 h of DI, and 30min post. The non-standing spinal length was evaluated on the bath lifting platform using a bespoke stadiometer before and following DI. DI significantly modulated m. erector spinae viscoelastic properties at L4, L1, T11, and T9 with no effect of laterality. Bilateral tissue tone was significantly reduced after 1 and 6 h DI at L4, L1, T11, and T9 to a similar extent. Stiffness was also reduced by DI at 1 h but partially recovered at 6 h for L4, L1, and T11. Creep was increased by DI at 1 h, with partial recovery at 6 h, although only T11 was significant. All properties returned to baseline 30 min following DI. Significant spinal elongation (1.17 ± 0.20 cm) with mild (at 1 h) to moderate (at 6 h) LBP was induced, mainly in the upper lumbar and lower thoracic regions. Spinal length increases positively correlated (Rho = 0.847, p = 0.024) with middle thoracic (T9) tone reduction, but with no other stiffness or creep changes. Spinal length positively correlated (Rho = 0.557, p = 0.039) with Max LBP; LBP failed to correlate with any m. erector spinae measured parameters. The DI-induced bilateral m. erector spinae tone, creep, and stiffness changes persist beyond 2 h. Evidence of spinal elongation and LBP allows suggesting that the trunk myofascial tissue changes could play a role in LBP pathogenesis observed in real and simulated microgravity. Further study is warranted with longer duration DI, assessment of IVD geometry, and vertebral column stability.

Brain Connectometry Changes in Space Travelers After Long-Duration Spaceflight.

Humans undergo extreme physiological changes when subjected to long periods of weightlessness, and as we continue to become a space-faring species, it is imperative that we fully understand the physiological changes that occur in the human body, including the brain. In this study, we present findings of brain structural changes associated with long-duration spaceflight based on diffusion magnetic resonance imaging (dMRI) data. Twelve cosmonauts who spent an average of six months aboard the International Space Station (ISS) were scanned in an MRI scanner pre-flight, ten days after flight, and at a follow-up time point seven months after flight. We performed differential tractography, a technique that confines white matter fiber tracking to voxels showing microstructural changes. We found significant microstructural changes in several large white matter tracts, such as the corpus callosum, arcuate fasciculus, corticospinal, corticostriatal, and cerebellar tracts. This is the first paper to use fiber tractography to investigate which specific tracts exhibit structural changes after long-duration spaceflight and may direct future research to investigate brain functional and behavioral changes associated with these white matter pathways.

Sharp Changes in Muscle Tone in Humans Under Simulated Microgravity.

A decrease in muscle tone induced by space flight requires a standardized assessment of changes to control the state of the neuromuscular system. This study is a step toward the development of a unified protocol, aimed at determining the initial effect of the presence or withdrawal of support on muscle tone, the effects of a 2-h supportlessness in Dry Immersion (DI) experiments, and the changes in muscle tone depending on the site of measurement. To perform measurements of changes in muscle tone, we used a MyotonPRO device. The list of muscles that we assessed includes: trunk - mm. deltoideus posterior, trapezius, erector spinae; leg - mm. biceps femoris, rectus femoris, tibialis anterior, soleus, gastrocnemius; foot - m. flexor digitorum brevis, tendo Achillis, aponeurosis plantaris. The study involved 12 healthy volunteers (6 men, 6 women) without musculoskeletal disorders and aged 32.8 ± 1.6 years. At the start of DI, there was a significant decrease in muscle tone of the following muscles: mm. tibialis anterior (-10.9%), soleus (-9.6%), erector spinae (-14.4%), and the tendo Achillis (-15.3%). The decrease continued to intensify over the next 2 h. In contrast, the gastrocnemius muscle demonstrated an increase in muscle tone (+7.5%) 2 h after the start of DI compared to the immediate in-bath baseline. Muscle tone values were found to be site-dependent and varied in different projections of mm. erector spinae and soleus. In previous experiments, we observed a high sensitivity of the myotonometry technique, which was confirmed in this study. To make it possible to compare data from different studies, a standardized protocol for measuring muscle tone for general use in gravitational physiology needs to be developed.

Sleep in 21-Day Dry Immersion. Are Cardiovascular Adjustments Rapid Eye Movement Sleep-Dependent?

Introduction: A decrease in sleep quality and duration during space missions has repeatedly been reported. However, the exact causes that underlie this effect remain unclear. In space, sleep might be impacted by weightlessness and its influence on cardiovascular function. In this study, we aimed at exploring the changes of night sleep architecture during prolonged, 21-day Dry Immersion (DI) as one of the ground-based models for microgravity studies and comparing them with adaptive changes in the cardiovascular system. Methods: Ten healthy young men were exposed to DI for 21 days. The day before (baseline, B-1), on the 3rd (DI3), 10th (DI10), and 19th (DI19) day of DI, as well as in the recovery period, 1 day after the end of DI (R + 1), they were subjected to overnight polysomnography (PSG) and ambulatory blood pressure monitoring. Results: On DI3, when the most severe back pain occurred due to the effects of DI on the spine and back muscles, the PSG data showed dramatically disorganized sleep architecture. Sleep latency, the number of awakenings, and the duration of wake after sleep onset (WASO) were significantly increased compared with the B-1. Furthermore, the sleep efficiency, duration of rapid eye movement sleep (REM), and duration of non-rapid eye movement stage 2 decreased. On DI10, subjective pain ratings declined to 0 and sleep architecture returned to the baseline values. On DI19, the REM duration increased and continued to rise on R + 1. An increase in REM was accompanied by rising in a nighttime heart rate (HR), which also shows the most significant changes after the end of DI. On DI19 and R + 1, the REM duration showed opposite correlations with the BP parameters: on DI19 it was negatively associated with the systolic BP (SBP), and on R + 1 it was positively correlated with the diastolic BP (DBP). Conclusion: An increase in REM at the end of DI and in recovery might be associated with regulatory changes in the cardiovascular system, in particular, with the reorganization of the peripheral and central blood flow in response to environmental changes.

The First Female Dry Immersion (NAIAD-2020): Design and Specifics of a 3-Day Study.

This article describes procedures and some results of the first study of females undergoing 3-day Dry Immersion. The experiment "NAIAD-2020" was carried out at the Institute of Biomedical Problems (Moscow, Russia) with the participation of six healthy women volunteers (age 30.17 ± 5.5 years, height 1.66 ± 0.1 m, weight 62.05 ± 8.4 kg, BMI 22.39 ± 2.2 kg/m2) with a natural menstrual cycle. During the study, a standard protocol was used, the same as for men, with a minimum period of time spent outside the immersion bath. Before, during and after Immersion, 22 experiments were carried out aimed at studying the neurophysiological, functional, metabolic and psychophysiological functions of the body, the results of which will be presented in future publications. The total time outside the bath for women did not exceed that for men. Systolic and diastolic pressure did not significantly change during the immersion. In the first 24 h after the end of the immersion, heart rate was significantly higher than the background values [F(4,20) = 14.67; P < 0.0001]. Changes in body temperature and water balance were consistent with the patterns found in men. No significant changes in height and weight were found during immersion. All women reported general discomfort and pain in the abdomen and back. The results of this study did not find significant risks to women's health and showed the feasibility of using this model of the effects of space flight in women of reproductive age.

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.

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.

Dry Immersion as a Ground-Based Model of Microgravity Physiological Effects.

Dry immersion (DI) is one of the most widely used ground models of microgravity. DI accurately and rapidly reproduces most of physiological effects of short-term space flights. The model simulates such factors of space flight as lack of support, mechanical and axial unloading as well as physical inactivity. The current manuscript gathers the results of physiological studies performed from the time of the model's development. This review describes the changes induced by DI of different duration (from few hours to 56 days) in the neuromuscular, sensory-motor, cardiorespiratory, digestive and excretory, and immune systems, as well as in the metabolism and hemodynamics. DI reproduces practically the full spectrum of changes in the body systems during the exposure to microgravity. The numerous publications from Russian researchers, which until present were mostly inaccessible for scientists from other countries are summarized in this work. These data demonstrated and validated DI as a ground-based model for simulation of physiological effects of weightlessness. The magnitude and rate of physiological changes during DI makes this method advantageous as compared with other ground-based microgravity models. The actual and potential uses of the model are discussed in the context of fundamental studies and applications for Earth medicine.

Alterations of Functional Brain Connectivity After Long-Duration Spaceflight as Revealed by fMRI.

The present study reports alterations of task-based functional brain connectivity in a group of 11 cosmonauts after a long-duration spaceflight, compared to a healthy control group not involved in the space program. To elicit the postural and locomotor sensorimotor mechanisms that are usually most significantly impaired when space travelers return to Earth, a plantar stimulation paradigm was used in a block design fMRI study. The motor control system activated by the plantar stimulation involved the pre-central and post-central gyri, SMA, SII/operculum, and, to a lesser degree, the insular cortex and cerebellum. While no post-flight alterations were observed in terms of activation, the network-based statistics approach revealed task-specific functional connectivity modifications within a broader set of regions involving the activation sites along with other parts of the sensorimotor neural network and the visual, proprioceptive, and vestibular systems. The most notable findings included a post-flight increase in the stimulation-specific connectivity of the right posterior supramarginal gyrus with the rest of the brain; a strengthening of connections between the left and right insulae; decreased connectivity of the vestibular nuclei, right inferior parietal cortex (BA40) and cerebellum with areas associated with motor, visual, vestibular, and proprioception functions; and decreased coupling of the cerebellum with the visual cortex and the right inferior parietal cortex. The severity of space motion sickness symptoms was found to correlate with a post- to pre-flight difference in connectivity between the right supramarginal gyrus and the left anterior insula. Due to the complex nature and rapid dynamics of adaptation to gravity alterations, the post-flight findings might be attributed to both the long-term microgravity exposure and to the readaptation to Earth's gravity that took place between the landing and post-flight MRI session. Nevertheless, the results have implications for the multisensory reweighting and gravitational motor system theories, generating hypotheses to be tested in future research.

Cortical reorganization in an astronaut's brain after long-duration spaceflight.

To date, hampered physiological function after exposure to microgravity has been primarily attributed to deprived peripheral neuro-sensory systems. For the first time, this study elucidates alterations in human brain function after long-duration spaceflight. More specifically, we found significant differences in resting-state functional connectivity between motor cortex and cerebellum, as well as changes within the default mode network. In addition, the cosmonaut showed changes in the supplementary motor areas during a motor imagery task. These results highlight the underlying neural basis for the observed physiological deconditioning due to spaceflight and are relevant for future interplanetary missions and vestibular patients.