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| Two-dimensional ocular ultrasonography. Optic nerve sheath diameter (ONSD) was measured 3 mm behind the posterior globe.
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Neuro-ophthalmological changes named spaceflight associated neuro-ocular syndrome (SANS) reported after spaceflights are important medical issues. Dry immersion (DI), an analog to microgravity, rapidly induces a centralization of body fluids, immobilization, and hypokinesia similar to that observed during spaceflight. The main objectives of the pre...
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... probe was placed on the eyelid and adjusted to obtain an appropriate display of the optic nerve into the globe. The assessment was realized in a two-dimensional mode and ONSD was measured 3 mm behind the ocular globe ( Figure 5). The right and left optic nerves were assessed, and one measure was performed for each eye in the sagittal plane. ...
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After exposure to microgravity, astronauts undergo microgravity-induced thoraco-cephalic fluid shift, which may lead to ocular changes called “spaceflight associated neuro-ocular syndrome” (SANS). The onset of SANS may be multifactorial, including a potential elevation in intracranial pressure. Moreover, little is known about the impact of spacefli...
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... Few studies have determined the impact of DI on eye structure. However, our group observed an enlargement in optic nerve sheath diameter, an indirect surrogate marker of ICP, during short-term DI 15,16 . Ocular changes were also reported after head-down bed rest (HDBR) 17 , along with some isolated cases of optic disc oedema 3 . ...
... Choroidal folds and optic disc oedema persisted over 1 year 25 . Consistently with our previous study performed in similar conditions in DI in men 16 , we observed an increase in pRNFLT. In a previous study, spectralis OCT revealed an average increase in peripapillary retinal thickness (~5%) after a 30-day HDBR in a 25-year-old Caucasian male without noticeable presence of optic disc oedema 26 . ...
... In our study, we did not observe any significant changes in IOP. These results are consistent with our previous study, where IOP was preserved in healthy male volunteers who underwent 5 days of DI 16 . In a 7-day HDBR, a decrease in IOP was observed during the 5 th and 7 th day in 8 female volunteers. ...
After exposure to microgravity, astronauts undergo microgravity-induced thoraco-cephalic fluid shift, which may lead to ocular changes called “spaceflight associated neuro-ocular syndrome” (SANS). The onset of SANS may be multifactorial, including a potential elevation in intracranial pressure. Moreover, little is known about the impact of spaceflight on SANS in women due to the fact that fewer female astronauts have spent time in long-term missions. The objective is to determine whether similar ophthalmological changes occur in healthy women after short-term exposure to microgravity. The auto-refractometer was used to determine objective refraction. The best corrected distance visual acuity was assessed with a Monoyer chart. The ocular axial length was assessed using optical biometry. The applanation tonometry was used to determine intraocular pressure. Peripapillary retinal nerve fibre layer thickness (pRNFLT), macular total retinal thickness, and ganglion cell complex (GCC) were measured using optical coherence tomography. Ocular axial length is reduced after DI. pRNFL is thickest after DI specifically in the temporal, temporal-inferior, and nasal-inferior quadrants. Macular total retinal at the inferior quadrant of the 6-mm ring is thickest after DI. Global GCC is thinnest after DI. In this study, 5 days of DI induces slight but significant ophthalmological changes in women. However, these subtle changes do not correspond to criteria defined in SANS.
... In this experiment DI provoked a slight but significant increase in retinal nerve fiber layer thickness (RNFLT) in the temporal quadrant and an enlargement in ONSD. Thigh cuffs tended to limit the ONSD enlargement but failed to prevent the increase in RNFLT 38,39 . ...
Long-duration human spaceflight can lead to changes in both the eye and the brain, which have been referred to as Spaceflight Associated Neuro-ocular Syndrome (SANS). These changes may manifest as a constellation of symptoms, which can include optic disc edema, optic nerve sheath distension, choroidal folds, globe flattening, hyperopic shift, and cotton wool spots. Although the underpinning mechanisms for SANS are not yet known, contributors may include intracranial interstitial fluid accumulation following microgravity induced headward fluid shift. Development and validation of SANS countermeasures contribute to our understanding of etiology and accelerate new technology including exercise modalities, Lower Body Negative Pressure suits, venous thigh cuffs, and Impedance Threshold Devices. However, significant knowledge gaps remain including biomarkers, a full set of countermeasures and/or treatment regimes, and finally reliable ground based analogs to accelerate the research. This review from the European Space Agency SANS expert group summarizes past research and current knowledge on SANS, potential countermeasures, and key knowledge gaps, to further our understanding, prevention, and treatment of SANS both during human spaceflight and future extraterrestrial surface exploration.
... The study (DI-5-CUFFS) was conducted at the MEDES space clinic, Toulouse, France, from November 19, 2018 to March 23, 2019. Ten scientific teams took part in the study, for which some results were previously published (18,21,22). The general study protocol is detailed by Robin et al. (21). ...
... Our hypothesis was that thoraco-cephalic fluid shift, which is potentially related to spaceflight-associated neuro-ocular syndrome (i.e., SANS), would influence the morphology of the spinal canal and the position of the spinal cord. A previous study reports changes in optic nerve sheath diameter after 5 days of DI and a slight effect of thigh cuffs (22). However, we did not observe changes at any investigated vertebral level, indicating that this fluid shift may not be detectable by MRI morphological analysis of the spinal canal. ...
... An increase in ADC occurs along with inflammation and may be regarded as a sensitive marker of tissue damage or degenerative changes (28). A change in ADC during DI could be explained by a fluid shift from the lumbar to the thoraco-cephalic area, which is involved in the pathogenesis of SANS (22), but this possibility may be unlikely because we observed no increase in ADC at the L 3 to S 1 levels. Instead, we postulate that the increase in ADC observed at the L 1 and L 2 levels, as well as initial back pain, could be explained by local inflammation due to spinal flattening or nerve stretching subsequent to an increase in IVD height. ...
Astronauts frequently report microgravity-induced back pain, which is generally more pronounced in the beginning of a spaceflight. The dry immersion (DI) model reproduces the early effects of microgravity in terms of global support unloading and fluidshift, both of which are involved in back pain pathogenesis. Here, we assessed spinal changes induced by exposure to 5 days of strict DI in 18 healthy men (25-43 years old) with (n = 9) or without (n = 9) thigh cuffs countermeasure. Intervertebral disc (IVD) height, spinal cord position, and apparent diffusion coefficient (ADC; reflecting global water motion) were measured using magnetic resonance imaging before and after DI. After DI, IVD height increased in thoracic (+3.3 ± 0.8 mm; C7-T12) and lumbar (+4.5 ± 0.4 mm; T12-L5) regions but not in the cervical region (C2-C7) of the spine. An increase in ADC after DI was observed at the L1 (~6% increase, from 3.2 to 3.4 × 10-3 mm2/s; p < 0.001) and L2 (~3% increase, from 3.4 to 3.5 × 10-3 mm2/s; p = 0.005) levels. There was no effect of thigh cuffs on spinal parameters. This change in IVD after DI follows the same "gradient" pattern of height increase from the cervical to the lumbar region as observed after bedrest and spaceflight. The increase in ADC at L1 level positively correlated with reported back pain. These findings emphasize the utility of the DI model for studying early spinal changes observed in microgravity.
... This integrative study was primarily designed to test the efficacy of venoconstrictive thigh cuffs, as countermeasure to limit cephalad fluidshift, on DI-induced deconditioning, in particular for body fluids and related ophthalmological disorders (for results cf. Robin et al., 2020;Kermorgant et al., 2021). However, several physiological systems interact, including the cardiovascular and musculoskeletal systems. ...
... The main limitation of this study is the low number of subjects in each group (n = 9). The number of subjects was not specifically powered for bone metabolism criteria, but for change in optic nerve sheath diameter, a primary outcome measure for this protocol (ck Kermorgant et al., 2021). This might have been responsible for the lack of significant changes, as seen for example in Glu-OC since statistical difference was achieved with the unique group of 12 subjects in the 1st experiment . ...
Background: The dry immersion (DI) model closely reproduces factors of spaceflight environment such as supportlessness, mechanical and axial unloading, physical inactivity, and induces early increased bone resorption activity and metabolic responses as well as fluid centralization. The main goal of this experiment was to assess the efficacity of venoconstrictive thigh cuffs, as countermeasure to limit cephalad fluidshift, on DI-induced deconditioning, in particular for body fluids and related ophthalmological disorders. Our specific goal was to deepen our knowledge on the DI effects on the musculoskeletal events and to test whether intermittent counteracting fluid transfer would affect DI-induced bone modifications.
Methods: Eighteen males divided into Control (DI) or Cuffs (DI-TC) group underwent an unloading condition for 5 days. DI-TC group wore thigh cuffs 8–10 h/day during DI period. Key markers of bone turnover, phospho-calcic metabolism and associated metabolic factors were measured.
Results: In the DI group, bone resorption increased as shown by higher level in Tartrate-resistant acid phosphatase isoform 5b at DI 24h . C-terminal telopeptide levels were unchanged. Bone formation and mineralization were also affected at DI 24h with a decreased in collagen type I synthesis and an increased bone-specific alkaline phosphatase. In addition, osteocalcin and periostin levels decreased at DI 120h . Calcemia increased up to a peak at DI 48h , inducing a trend to decrease in parathyroid hormone levels at DI 120h . Phosphatemia remained unchanged. Insulin-like growth factor 1 and visfatin were very sensitive to DI conditions as evidenced by higher levels by 120% vs. baseline for visfatin at DI 48h . Lipocalin-2, a potential regulator of bone homeostasis, and irisin were unchanged. The changes in bone turnover markers were similar in the two groups. Only periostin and visfatin changes were, at least partially, prevented by thigh cuffs.
Conclusion: This study confirmed the rapid dissociation between bone formation and resorption under DI conditions. It revealed an adaptation peak at DI 48h , then the maintenance of this new metabolic state during all DI. Notably, collagen synthesis and mineralisation markers evolved asynchronously. Thigh cuffs did not prevent significantly the DI-induced deleterious effects on bone cellular activities and/or energy metabolism.
... DI studies focused on the interactions between the visual, vestibular, and motor systems . However, Kermorgant and colleagues successfully employed ocular ultrasound and Spectral domain OCT to document optic nerve sheath diameter and retinal nerve fiber layer thickness changes, respectively, in healthy human subjects exposed to short-duration (3e5 days) DI (Kermorgant et al., 2017, Kermorgant et al., 2021. This indicates the potential value of DI for the study of SANS. ...
The optic nerve and retinal abnormalities seen in Spaceflight Associated Neuro-Ocular Syndrome (SANS) are likely to involve imbalances of intraocular pressure (IOP) and intracranial pressure (ICP). In this chapter, we briefly summarize the changes in IOP and ICP, which occur during spaceflight. Next, we describe IOP–ICP relationships at the optic nerve head in health and disease, highlighting the importance of the translaminar pressure difference (TLPD), which is defined as the difference between IOP and ICP (IOP − ICP). Finally, we review the theoretical and experimental basis for SANS countermeasures that are based on the manipulation of IOP or ICP to correct an abnormal TLPD. In this last section, we discuss recent literature in both animals and humans to address the validity of this approach, as well as potential pitfalls.
... During 3-day DI, Kermorgant et al. (2017) showed an increase in ONSD of about 30%, as measured with ultrasound (Pre-DI: 4.64 ± 0.40 mm; DI3: 6.01 ± 0.49 mm; p < 0.001; Kermorgant et al., 2017). In DI5-CUFFS, Kermorgant et al. (2021) have found a significant increase of ONSD after 5 days of DI by 20% in the control group and 14% in the cuffs group (Kermorgant et al., 2021). These ONSD values are equivalent to an elevation of ICP around 20 mmHg, the normal range being between 7 and 15 mmHg (Geeraerts et al., 2008). ...
... During 3-day DI, Kermorgant et al. (2017) showed an increase in ONSD of about 30%, as measured with ultrasound (Pre-DI: 4.64 ± 0.40 mm; DI3: 6.01 ± 0.49 mm; p < 0.001; Kermorgant et al., 2017). In DI5-CUFFS, Kermorgant et al. (2021) have found a significant increase of ONSD after 5 days of DI by 20% in the control group and 14% in the cuffs group (Kermorgant et al., 2021). These ONSD values are equivalent to an elevation of ICP around 20 mmHg, the normal range being between 7 and 15 mmHg (Geeraerts et al., 2008). ...
Microgravity induces a cephalad fluid shift that is responsible for cephalic venous stasis that may increase intracranial pressure (ICP) in astronauts. However, the effects of microgravity on regional cerebral blood flow (rCBF) are not known. We therefore investigated changes in rCBF in a 5-day dry immersion (DI) model. Moreover, we tested thigh cuffs as a countermeasure to prevent potential microgravity-induced modifications in rCBF. Around 18 healthy male participants underwent 5-day DI with or without a thigh cuffs countermeasure. They were randomly allocated to a control (n=9) or cuffs (n=9) group. rCBF was measured 4days before DI and at the end of the fifth day of DI (DI5), using single-photon emission computed tomography (SPECT) with radiopharmaceutical 99mTc-hexamethyl propylene amine oxime (99mTc-HMPAO). SPECT images were processed using statistical parametric mapping (SPM12) software. At DI5, we observed a significant decrease in rCBF in 32 cortical and subcortical regions, with greater hypoperfusion in basal ganglia (right putamen peak level: z=4.71, puncorr<0.001), bilateral occipital regions (left superior occipital peak level: z=4.51, puncorr<0.001), bilateral insula (right insula peak level: 4.10, puncorr<0.001), and bilateral inferior temporal (right inferior temporal peak level: 4.07, puncorr<0.001). No significant difference was found between the control and cuffs groups on change in rCBF after 5days of DI. After a 5-day DI, we found a decrease in rCBF in cortical and subcortical regions. However, thigh cuffs countermeasure failed to prevent hypoperfusion. To date, this is the first study measuring rCBF in DI. Further investigations are needed in order to better understand the underlying mechanisms in cerebral blood flow (CBF) changes after exposure to microgravity.
... After five days of DI, participants were found to have a loss in muscle strength, muscle fiber atrophy, impaired protein balance, and decreased oxidative capacity, regardless of the use of a thigh cuff. In contrast, measurements on cardiovascular and ophthalmological function carried out by our collaborators have shown a beneficial effect of the thigh cuff to prevent the adverse effects of body fluid redistribution induced by 5 days of DI [30][31][32]. ...
Muscle deconditioning is a major consequence of a wide range of conditions from spaceflight to a sedentary lifestyle, and occurs as a result of muscle inactivity, leading to a rapid decrease in muscle strength, mass, and oxidative capacity. The early changes that appear in the first days of inactivity must be studied to determine effective methods for the prevention of muscle deconditioning. To evaluate the mechanisms of muscle early changes and the vascular effect of a thigh cuff, a five-day dry immersion (DI) experiment was conducted by the French Space Agency at the MEDES Space Clinic (Rangueil, Toulouse). Eighteen healthy males were recruited and divided into a control group and a thigh cuff group, who wore a thigh cuff at 30 mmHg. All participants underwent five days of DI. Prior to and at the end of the DI, the lower limb maximal strength was measured and muscle biopsies were collected from the vastus lateralis muscle. Five days of DI resulted in muscle deconditioning in both groups. The maximal voluntary isometric contraction of knee extension decreased significantly. The muscle fiber cross-sectional area decreased significantly by 21.8%, and the protein balance seems to be impaired, as shown by the reduced activation of the mTOR pathway. Measurements of skinned muscle fibers supported these results and potential changes in oxidative capacity were highlighted by a decrease in PGC1-α levels. The use of the thigh cuff did not prevent muscle deconditioning or impact muscle function. These results suggest that the major effects of muscle deconditioning occur during the first few days of inactivity, and countermeasures against muscle deconditioning should target this time period. These results are also relevant for the understanding of muscle weakness induced by muscle diseases, aging, and patients in intensive care.
Long-duration spaceflight (LDSF) is associated with unique hazards and linked with numerous human health risks including Spaceflight Associated Neuro-ocular Syndrome (SANS). The proposed mechanisms for SANS include microgravity induced cephalad fluid shift and increased Intracranial Pressure (ICP). SANS is a disorder seen only after LDSF and has no direct terrestrial pathologic counterpart as the zero G environment cannot be completely replicated on Earth. Head-down tilt, bed rest studies however have been used as a terrestrial analog and produce the cephalad fluid shift. Some proposed countermeasures for SANS include vasoconstrictive thigh cuffs and lower body negative pressure. Another potential researched countermeasure is the impedance threshold device (ITD) which can reduce ICP. We review the mechanisms of the ITD and its potential use as a countermeasure for SANS.
Astronauts in microgravity experience multi-system deconditioning, impacting their inflight efficiency and inducing dysfunctions upon return to Earth gravity. To fill the sex gap of knowledge in the health impact of spaceflights, we simulate microgravity with a 5-day dry immersion in 18 healthy women (ClinicalTrials.gov Identifier: NCT05043974). Here we show that dry immersion rapidly induces a sedentarily-like metabolism shift mimicking the beginning of a metabolic syndrome with a drop in glucose tolerance, an increase in the atherogenic index of plasma, and an impaired lipid profile. Bone remodeling markers suggest a decreased bone formation coupled with an increased bone resorption. Fluid shifts and muscular unloading participate to a marked cardiovascular and sensorimotor deconditioning with decreased orthostatic tolerance, aerobic capacity, and postural balance. Collected datasets provide a comprehensive multi-systemic assessment of dry immersion effects in women and pave the way for future sex-based evaluations of countermeasures.
Long-duration spaceflight is associated with neurologic and ophthalmic clinical and imaging findings in astronauts termed spaceflight associated neuro-ocular syndrome (SANS). These microgravity-induced findings have been well documented by the National Aeronautics and Space Administration (NASA) and are clearly a potential risk for future human space exploration. The underlying pathogenesis of SANS is not well understood, although multiple hypotheses have emerged. Terrestrial analogues and potential countermeasures have also been studied to further understand and potentially mitigate SANS. In this manuscript, we review the current understanding of SANS, discuss the prevailing hypotheses for pathogenesis, and describe current developments in terrestrial analogues and potential countermeasures for SANS.
