**3.9 Spaceflight-associated neuro-ocular syndrome (SANS)**

Several physiological and pathological neuro-ocular findings in astronauts/ cosmonauts during and after long-term spaceflight, including hyperoptic shifts up to +1.75 diopters, optic disc edema (swelling), globe (eyeball) flattening, choroidal folds, and "cotton wool" spots in the fundus oculi, have been reported [29]. These findings have been documented as spaceflight-associated neuro-ocular syndrome. NASA has investigated the clinical, ultrasound, optical coherence tomography imaging, and fundus oculi findings of the above symptoms. In 2016, out of 47 or 64 astronauts examined, approximately 10 developed SANS (disc edema in 10/64, cotton wool spot in 7/64, choroidal folds in 11/47, globe flattening in 12/47, and refractive error in 9/47). It is unlikely that the duration of spaceflight is unrelated [30].

The exact cause of SANS has not been clarified, but its development is likely related to the increase in intracranial pressure due to the cephalad fluid shift. The increase in intracranial pressure is not necessarily due to microgravity exposure, but some percentage of astronauts had intracranial pressure change and developed SANS [29, 30].

**19**

*Effects of Microgravity on Human Physiology DOI: http://dx.doi.org/10.5772/intechopen.90700*

**3.11 Effects of artificial gravity**

**4. Musculoskeletal system**

the Moon or Moon base, or a Martian expedition.

**3.10 Brain structural plasticity during spaceflight**

Several countermeasures, e.g., lower body negative pressure, thigh cuffs, an impedance threshold device (ITD), vitamin B group administration, and artificial gravity, have been considered and are under trial. NASA and collaborating researchers continue to investigate SANS in preparation for future manned missions to space, including continued trips to the ISS, deep space gateway missions, a return to

In 2016, structural changes in the brain during spaceflight were reported. Koppelmans et al. [31] evaluated retrospective longitudinal T2-weighted MRI scans and balance data from 27 astronauts (13, ~2-week Shuttle crew members, and 14, ~6-month ISS crew members) to assess spaceflight effects on brain structure. They observed extensive volumetric gray matter decreases, including large areas covering the temporal and frontal poles and around the orbits, and the effects were larger in ISS members than in Shuttle crew members. There were also bilateral focal gray matter increases within the medial primary somatosensory and motor cortex. In 2017, a review on these MRI changes associated with spaceflight (actual or simulated) was reported. Van Ombergen et al. [32] discussed neuroplastic changes in the central nervous system and concluded that the cerebellum, cortical motor areas, and vestibular-related pathways are highly involved, demonstrating that these brain regions are indeed affected by actual and simulated spaceflight. Structural studies are now in progress, and functional relationships are under investigation. Long-term studies will be necessary to clarify the mechanism.

We tested an intermittent short-arm centrifuge of 1.4 G with 60-W ergometric exercise with a step-up increase of 0.2 G and 15 W, respectively, for 30 min every day for 21 days during −6° head-down bedrest [33]. The circulatory blood volume was reduced by 20% in the control subjects, but no reduction was observed in the countermeasure subjects. Cardiac output and stroke volume were not changed in the countermeasure subjects, but they decreased in the control subjects. The baseline level of muscle sympathetic nerve activity (MSNA) was not changed in the

Therefore, everyday ergometric exercise under artificial gravity maintains the

The first muscular measurements were performed in Skylab and Space Shuttle missions by the United States and in Salyut and Mir by the Soviet Union [34–37]. The most prominent muscle loss was observed in the calf muscle (the soleus and gastrocnemius) after a few weeks in space. The muscle loss exhibited interindividual variation, but the maximum loss reached as high as 10%. This volume loss in the lower extremities accounts for most of the muscle atrophy and the blood and interstitial fluid shift. Although fluid shift away from the legs influences the size of these muscles, this phenomenon alone cannot explain the changes in leg volume on MRI. Muscle atrophy appears rapidly, usually between 8 and 11 days of flight,

countermeasure subjects, but it increased in the control subjects.

preflight cardiovascular state without adapting to microgravity.

**4.1 Mechanism of muscle loss under microgravity**

### *Effects of Microgravity on Human Physiology DOI: http://dx.doi.org/10.5772/intechopen.90700*

*Beyond LEO - Human Health Issues for Deep Space Exploration*

the orthostatic tolerance, albeit not completely.

**3.8 Cardiovascular deconditioning**

have also been explored.

and multiple factors act in concert.

**3.9 Spaceflight-associated neuro-ocular syndrome (SANS)**

intolerance.

Reduction of the circulatory blood volume is the most important factor for postflight orthostatic intolerance. The decrease in stroke volume after spaceflight reflects this circulatory blood volume loss. Although this is the main cause, the recovery of circulatory blood volume to the normal state is not complete. The crew members are recommended to take 8 g of salt and 1 L of water, which ameliorates

Another factor is the limitation by vasoconstriction. The postflight blood pressure of non-finishers cannot be increased by the total peripheral resistance compared with the preflight state. During the postflight upright standing 70° tilt test, the total peripheral resistance cannot increase despite activation of muscle sympathetic nerve activity, probably due to the alterations in venoarterial reflex and smooth muscle atrophy of the resistant vessels. Overall, circulatory blood volume reduction and attenuated vasoconstriction are the main factors for orthostatic

What is the cause of this cardiovascular deconditioning? NASA's criteria of orthostatic intolerance are (1) presyncopal symptoms (pallor, cold sweat, nausea, blackout, and fainting), (2) gradual systolic blood pressure decrease <80 mmHg, (3) sudden systolic blood pressure decrease >15 mmHg, or (4) sudden heart rate decrease >15 bpm while on the 70° tilt bed for 15 min. A recent report stated that 65% of astronauts satisfied these criteria. Previously, this cardiovascular deconditioning was considered to be solely due to circulatory fluid loss, but other causes

In addition to the decrease in circulatory blood volume, other causes, i.e., altered arterial baroreflex gain, altered leg venous volume, easy fluid pooling in the space of atrophied skeletal muscles, attenuated muscle pump effects due to skeletal muscle atrophy, hypersensitivity of β-adrenergic receptors, and altered influence of vestibular (especially otolith) input, have been considered. Moreover, increased venous permeability of lower leg vessels and attenuated cardiopulmonary volume receptor reflex after −6° head-down tilt for 14 days were observed in our bedrest experiment. These changes are not the only cause of cardiovascular deconditioning,

Several physiological and pathological neuro-ocular findings in astronauts/ cosmonauts during and after long-term spaceflight, including hyperoptic shifts up to +1.75 diopters, optic disc edema (swelling), globe (eyeball) flattening, choroidal folds, and "cotton wool" spots in the fundus oculi, have been reported [29]. These findings have been documented as spaceflight-associated neuro-ocular syndrome. NASA has investigated the clinical, ultrasound, optical coherence tomography imaging, and fundus oculi findings of the above symptoms. In 2016, out of 47 or 64 astronauts examined, approximately 10 developed SANS (disc edema in 10/64, cotton wool spot in 7/64, choroidal folds in 11/47, globe flattening in 12/47, and refractive error in 9/47). It is unlikely that the duration of spaceflight is unrelated [30]. The exact cause of SANS has not been clarified, but its development is likely related to the increase in intracranial pressure due to the cephalad fluid shift. The increase in intracranial pressure is not necessarily due to microgravity exposure, but some percentage of astronauts had intracranial pressure change and developed

**18**

SANS [29, 30].

Several countermeasures, e.g., lower body negative pressure, thigh cuffs, an impedance threshold device (ITD), vitamin B group administration, and artificial gravity, have been considered and are under trial. NASA and collaborating researchers continue to investigate SANS in preparation for future manned missions to space, including continued trips to the ISS, deep space gateway missions, a return to the Moon or Moon base, or a Martian expedition.
