Spaceflight-associated Neuro-ocular Syndrome Research Articles

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.

Ground-Based Analogs for Human Spaceflight.

This mini-review provides an updated summary of various analogs for adaptations of humans to the microgravity of space. Microgravity analogs discussed in this paper include dry immersion, wet immersion, unilateral lower-extremity limb suspension, head down tilt (HDT), and supine bed rest. All Earth-based analogs are imperfect simulations of microgravity with their own advantages and disadvantages. This paper compares these five frequently used microgravity analogs to offer insights into their usefulness for various physiological systems. New developments for each human microgravity analog are explored and advantages of one analog are evaluated against other analogs. Furthermore, the newly observed risk of Spaceflight Associated Neuro-Ocular Syndrome (SANS) is included in this mini review with a discussion of the advantages and disadvantages of each method of simulation for the relatively new risk of SANS. Overall, the best and most integrated analog for Earth-based studies of the microgravity of space flight appears to be head-down tilt bed rest.

From human terrestrial models to new preventive measures for ocular changes in astronauts : Results of the German Aerospace Center studies

Ocular changes in astronauts, particularly the spaceflight associated neuro-ocular syndrome (SANS), pose amedical challenge for which no suitable preventive measures exist. During long-duration spaceflight missions, e.g. to the Moon and Mars, SANS and radiation-induced cataract could affect the health and performance of crews and jeopardize the success of missions. Mechanistic studies and development of preventive measures require suitable terrestrial models. Overview on the most recent research and future plans in space medicine. Search for relevant publications using PubMed. Bed rest studies at the German Aerospace Center (DLR) demonstrated that strict bed rest in a -6° head down tilt position reproduces changes just like SANS on Earth. This model including creation of optic disc edema is applied in human studies testing influences of artificial gravity through short arm centrifugation as apreventive method. The unique research facility :envihab provides the opportunity to also simulate the ambient conditions of the International Space Station during bed rest studies. Future head down tilt bed rest studies will serve to systematically test preventive measures for SANS. Similar investigations would be difficult to realize under real space conditions. Through close collaboration between space medicine and terrestrial ophthalmology, this research can benefit patients on Earth.

Dependency of intraocular pressure on body posture in glaucoma patients : New approaches to pathogenesis and treatment

Human intraocular pressure (IOP) depends on the position of the head in relation to the body in space. Physiologically, the IOP increases in alying position compared to an upright posture. Microgravity in space also appears to cause an increase in intraocular pressure, accompanied by other ophthalmological changes, which are summarized under the term spaceflight associated neuro-ocular syndrome (SANS). Bed rest studies are being carried out to investigate the effects of weightlessness on the human body. So here there is an intersection between research into SANS and glaucoma. Increased intraocular pressure remains the most important risk factor for glaucoma development and progression that can be influenced by treatment. The influence of position-dependent IOP fluctuations on glaucoma is still not sufficiently understood. A literature search was carried in PubMed on the subject of IOP fluctuations related to posture. Analysis and evaluation of the published study results and a summary of available clinical data. The increase in IOP when changing from aseated to alying body position is greater in glaucoma patients with an increase of up to 8.6 mm Hg compared to healthy subjects with an increase up to 5 mm Hg. In small pilot studies the increase in lying IOP in some glaucoma patients and healthy volunteers could be attenuated by elevation of the head by 30%. Alower compartmental pressure in the subarachnoid space has been associated with glaucoma and may represent arisk factor for glaucoma development. Not only the level of IOP but also IOP fluctuations were associated with an increased risk of disease progression. The clinical significance of IOP peaks during sleep on glaucoma is still not sufficiently understood. New methods for continuous IOP measurement offer promising opportunities for further research into the importance of IOP fluctuations related to changes of body and head posture.

Visual changes after space flight: is it really caused by increased intracranial tension? A systematic review

Spaceflight-Associated Neuro-ocular Syndrome (SANS) was linked to increased intracranial pressure (ICP) attributable to the combined effects of microgravity and environmental conditions encountered during spaceflight. Microgravity countermeasures as lower body negative pressure (LBNP) are potential interventions for SANS. Our aim is to provide a comprehensive qualitative analysis of literature contrasting simulation and spaceflight studies, focusing on the pathophysiology of SANS, and highlighting gaps in current knowledge. We systematically searched PubMed electronic database for English primary research published until February 2019 discussing intracranial changes in spaceflight or simulated microgravity, excluding animal and experimental studies. Two authors screened all the abstracts with a third author resolving disagreements. The full-text manuscripts were analyzed in pilot-tested tables. Nineteen studies were reviewed; 13 simulation, and two out of six spaceflight studies were prospective. ICP changes were investigated in 11 simulation studies, where eight demonstrated a significant increase in ICP after variable periods of head-down tilt. three showed a significant increase in intraocular pressure (IOP) in conjunction with ICP elevation. With increasing ambient CO<inf>2</inf>: one showed an increase in IOP without further increase in ICP, while another showed a slight further decrease in ICP. LBNP demonstrated no significant effect on ICP in one and a decrease thereof in another study. After spaceflight, increased ICP on lumbar puncture was demonstrated in five studies. Exposure to microgravity increases ICP possibly precipitating ocular changes. Whether other factors come into play is the subject of investigation. Further randomized studies and methods of direct ICP measurement during spaceflight are needed.

Eye changes in space : New insights into clinical aspects, pathogenesis and prevention

More than ever research into changes in the eye caused by long-term space flight is becoming the focus of the international and national space agencies National Aeronautics and Space Administration (NASA), European Space Agency (ESA) and German Aerospace Center (DLR). In addition to space radiation-induced cataract formation considerable eye changes, summarized under space flight-associated neuro-ocular syndrome (SANS), can occur. This article gives an overview of the current state of research and future directions in the field of research concerned with ocular alterations in SANS and presents the relevance for terrestrial ophthalmological research. An analysis of existing publications on SANS in PubMed and reports on the risk of SANS published by the NASA of the USA was carried out. The reasons for the development of the eye changes in space have not been clarified. Factors such as the increase in intracranial pressure, fluid shifts, hypercapnia and genetic factors are the subject of intensive research efforts. Aterrestrial model for the induction of papilledema could be established (bed rest studies with -6° head-down tilt as aspace analogue). Countermeasures for the development of eye changes, such as intermittent artificial gravity, are the subject of current research studies. Research into SANS as part of bed rest studies will provide further important insights in the future for space research and also for terrestrial research. Clinical research projects can be derived from space research.

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.

Origins of Cerebral Edema: Implications for Spaceflight-Associated Neuro-Ocular Syndrome.

Spaceflight-associated neuro-ocular syndrome (SANS) was first described in 2011 and is associated with structural ocular changes found to occur in astronauts after long-duration missions. Despite multiple insufficient potential terrestrial models, an understanding of the etiology has yet to be described. A systematic review was conducted on literature published about the pathophysiology of cerebral edema. Databases searched include PubMed, Scopus, and the Texas Medical Center Online Library. This information was then applied to create theories on mechanisms on SANS etiology. Cerebral edema occurs through 2 general mechanisms: redistribution of ions and water intracellularly and displacement of ions and water from the vascular compartment to the brain parenchyma. These processes occur through interconnected endocrine and inflammatory pathways and involve mediators such as cytokines, matrix metalloproteases, nitric oxide, and free radicals. The pathways ultimately lead to a violation of cellular membrane ionic gradients and blood-brain barrier degradation. By applying the principles of cerebral edema pathophysiology to the optic disc edema (ODE) see in SANS, several theories regarding its etiology can be formed. Venous stasis may lead to ODE through venous and capillary distension and leak, as well as relative hypoxia and insufficient ATP substrate delivery causing axoplasmic flow stasis and local oxidative stress. Using the pathophysiology of cerebral edema as a model, hypotheses can be inferred as to the etiology of ODE in SANS. Further studies are needed to determine the presence and contribution of local vascular stasis and resulting inflammation and oxidative stress to the pathophysiology of SANS.

Spaceflight associated neuro-ocular syndrome.

Several decades of long duration space flight missions by the National Aeronautics and Space Administration has revealed an interesting and unique constellation of neuro-ophthalmic findings now called spaceflight associated neuro-ocular syndrome (SANS). The unique space environment of microgravity produces novel physiological changes and derangements that present a challenge to astronauts in current and future long duration space missions. Although the precise mechanism of SANS is not fully understood, in this review, we examine recent developments that may to help explain possible causes and potential countermeasures. The cause of SANS is still largely unknown. A growing body of evidence implicates multiple factors that contribute to the development of SANS including cephalad fluid shifts, increased intracranial pressure, venous/lymphatic stasis, inflammation, metabolism, axoplasmic stasis and radiation exposure. The pathologic mechanism behind SANS may be multifactorial and may be amenable to different countermeasures for prevention and management of SANS.

Assessing lymphatic route of CSF outflow and peripheral lymphatic contractile activity during head-down tilt using near-infrared fluorescence imaging.

Evidence overwhelmingly suggests that the lymphatics play a critical role in the clearance of cerebrospinal fluid (CSF) from the cranial space. Impairment of CSF outflow into the lymphatics is associated with a number of pathological conditions including spaceflight‐associated neuro‐ocular syndrome (SANS), a problem that limits long‐duration spaceflight. We used near‐infrared fluorescence lymphatic imaging (NIRFLI) to dynamically visualize the deep lymphatic drainage pathways shared by CSF outflow and disrupted during head‐down tilt (HDT), a method used to mimic the cephalad fluid shift that occurs in microgravity. After validating CSF clearance into the lymph nodes of the neck in swine, a pilot study was conducted in human volunteers to evaluate the effect of gravity on the flow of lymph through these deep cervical lymphatics. Injected into the palatine tonsils, ICG was imaged draining into deep jugular lymphatic vessels and subsequent cervical lymph nodes. NIRFLI was performed under HDT, sitting, and supine positions. NIRFLI shows that lymphatic drainage through pathways shared by CSF outflow are dependent upon gravity and are impaired under short‐term HDT. In addition, lymphatic contractile rates were evaluated from NIRFLI following intradermal ICG injections of the lower extremities. Lymphatic contractile activity in the legs was slowed in the gravity neutral, supine position, but increased under the influence of gravity regardless of whether its force direction opposed (sitting) or favored (HDT) lymphatic flow toward the heart. These studies evidence the role of a lymphatic contribution in SANS.

Optic Nerve Tortuosity on Earth and in Space.

INTRODUCTION: Spaceflight Associated Neuro-ocular Syndrome (SANS) results from long-duration spaceflight and presents with a constellation of signs (e.g., optic disc edema, choroidal folds, globe flattening, refractive error shifts, etc.). Optic nerve tortuosity (ONT) has been detected in approximately 47% of astronauts after long-duration spaceflight but has not yet been fully analyzed. This review examines terrestrial ONT in order to better understand how the condition is caused and measured.METHODS: References were identified by PubMed and ScienceDirect searches covering 1955 to October 2018 using the terms "optic nerve tortuosity," "optic nerve kinking," "optic disc torsion," "optic kinking," and "ocular torsion." Additional references were identified by searching relevant articles.RESULTS: ONT measurements have evolved and become more objective. One measure consists of meeting two criteria: 1) lack of optic nerve congruity in >1 coronal section; and 2) subarachnoid space dilation. This "criteria measure" is objective, sensitive, and specific for determining the presence of tortuosity. Another measure is the tortuosity index, which offers additional benefits by measuring the degree of ONT, including the potential to track changes over time. There are numerous terrestrial ONT causes, including intracranial hypertension, hydrocephalus, Chiari malformation, neurofibromatosis, glaucoma, and progeria, among others.DISCUSSION: To accurately measure ONT, it is crucial to adhere to objective, standardized techniques. The tortuosity index offers the potential to measure intraindividual change in ONT. Among the varied conditions associated with ONT, one commonality is pressure change. The impact of intracranial pressure on the vascular system and vice versa may offer insight into what is occurring in space.Scott RA, Tarver WJ, Brunstetter TJ, Urquieta E. Optic nerve tortuosity on Earth and in space. Aerosp Med Hum Perform. 2020; 91(2):91-97.

Evaluation of tablet-based methods for assessment of contrast sensitivity

Some astronauts have suffered degradation of vision during long-duration space flight, suffering from a condition that has come to be known as Spaceflight Associated Neuro-ocular Syndrome (SANS). While related morphological changes can be observed with imaging technologies such as optical coherence tomography (OCT), it may be useful to have a rapid method for functional vision assessment. In this paper, we compare three tablet-based methods for rapid assessment of contrast sensitivity. First, a relatively novel method developed expressly for touch screens, in which the subject “swipes” a frequency/contrast sweep grating to indicate the boundary between visible and invisible patterns; second, a method-of-adjustment task in which the subject adjusts the contrast of a grating patch up and down to bracket the visual threshold; and third, a traditional temporal two-alternative forced choice (2AFC) task, in which the subject is presented with a near-threshold stimulus in one of two intervals, and must report the interval containing the stimulus. The swipe method shows variability comparable to the 2AFC method, and shows good agreement in estimates of the spatial frequency of peak sensitivity. The absolute sensitivity estimated with the swipe method is higher than that of the other methods, perhaps because subjects are biased to trace outside of the visible pattern region, or perhaps due to stimulus differences.

Possible Factors Associated With Spaceflight-Associated Neuro-ocular Syndrome

Possible Factors Associated With Spaceflight-Associated Neuro-ocular Syndrome

Optic Disc Edema and Choroidal Engorgement in Astronauts During Spaceflight and Individuals Exposed to Bed Rest

Optic disc edema develops in astronauts during long-duration spaceflight and is a risk for all future astronauts during spaceflight. Having a ground-based analogue of weightlessness that reproduces critical features of spaceflight-associated neuro-ocular syndrome will facilitate understanding, preventing, and/or treating this syndrome. To determine whether the ocular changes in individuals exposed to an analogue of weightlessness are similar to the ocular changes in astronauts exposed to a duration of spaceflight comparable to this analogue of weightlessness. This cohort study, conducted from 2012 to 2018, investigated 11 healthy test participants before, during, and after 30 days of strict 6° head-down tilt bed rest as well as 20 astronauts before and during approximately 30 days of spaceflight. Data were collected at NASA Johnson Space Center, the German Aerospace Center, and on board the International Space Station. Statistical analysis was performed from February 13 to April 24, 2019. Peripapillary total retinal thickness and peripapillary choroid thickness quantified from optical coherence tomography images. Peripapillary total retinal thickness increased to a greater degree among 11 individuals (6 men and 5 women; mean [SD] age, 33.4 [8.0 years]) exposed to bed rest than among 20 astronauts (17 men and 3 women; mean [SD] age, 46.0 [6.0] years), with a mean difference between groups of 37 μm (95% CI, 13-61 μm; P = .005). Conversely, choroid thickness did not increase among the individuals exposed to bed rest but increased among the astronauts, resulting in a mean difference between groups of 27 μm (95% CI, 14-41 μm; P < .001). These findings suggest that strict head-down tilt bed rest produces a different magnitude of edema than occurs after a similar duration of spaceflight, and no change in choroid thickness. It is possible that a mild, long-term elevation in intracranial pressure experienced by individuals exposed to bed rest is greater than the intracranial pressure experienced by astronauts during spaceflight, which may explain the different severity of optic disc edema between the cohorts. Gravitational gradients that remain present during bed rest may explain the lack of increase in choroid thickness during bed rest, which differs from the lack of gravitational gradients during spaceflight. Despite the possibility that different mechanisms may underlie optic disc edema development in modeled and real spaceflight, use of this terrestrial model of spaceflight-associated neuro-ocular syndrome will be assistive in the development of effective countermeasures that will protect the eyes of astronauts during future space missions.

Brain Physiological Response and Adaptation During Spaceflight.

More than half of astronauts returning from long-duration missions on the International Space Station present with neuro-ocular structural and/or functional changes, including optic disc edema, optic nerve sheath distension, globe flattening, choroidal folds, or hyperopic shifts. This spaceflight-associated neuro-ocular syndrome (SANS) represents a major risk to future exploration class human spaceflight missions, including Mars missions. Although the exact pathophysiology of SANS is unknown, evidence thus far suggests that an increase in intracranial pressure (ICP) relative to the upright position on Earth, which is due to the loss of hydrostatic pressure gradients in space, may play a leading role. This review focuses on brain physiology in the spaceflight environment, specifically on how spaceflight may affect ICP and related indicators of cranial compliance, potential factors related to the development of SANS, and findings from spaceflight as well as ground-based spaceflight analog research studies.

A Novel Porcine Model for the Study of Cerebrospinal Fluid Dynamics: Development and Preliminary Results.

Idiopathic intracranial hypertension, space-flight associated neuro-ocular syndrome (SANS), and glaucoma are conditions that are among a spectrum of cerebrospinal fluid (CSF)-related ophthalmologic disease. This implies that local CSF pressures at the level of the optic nerve are involved to variable extent in these disease processes. However, CSF pressure measurements are problematic due to invasiveness and interpretation. The pressure measured by a lumbar puncture is likely not the same as the orbital CSF pressure. It is believed this is at least in part due to the flow restrictive properties of the optic canal. To investigate CSF flow within the orbit, a model for CSF dynamics was created using three medium-sized pigs. Contrast was administered through a lumbar subarachnoid space access. The contrast front was imaged with repeated computed tomographic (CT) imaging. Once contrast entered the orbit, rapid, sequential CT imaging was performed until the contrast reached the posterior globe. Head tilting was performed to highlight the role of gravitational dependence within the subarachnoid space.

Head Down Tilt Bed Rest Plus Elevated CO2 as a Spaceflight Analog: Effects on Cognitive and Sensorimotor Performance.

Long duration head down tilt bed rest (HDBR) has been widely used as a spaceflight analog environment to understand the effects of microgravity on human physiology and performance. Reports have indicated that crewmembers onboard the International Space Station (ISS) experience symptoms of elevated CO2 such as headaches at lower levels of CO2 than levels at which symptoms begin to appear on Earth. This suggests there may be combinatorial effects of elevated CO2 and the other physiological effects of microgravity including headward fluid shifts and body unloading. The purpose of the current study was to investigate these effects by evaluating the impact of 30 days of 6° HDBR and 0.5% CO2 (HDBR + CO2) on mission relevant cognitive and sensorimotor performance. We found a facilitation of processing speed and a decrement in functional mobility for subjects undergoing HDBR + CO2 relative to our previous study of HDBR in ambient air. In addition, nearly half of the participants in this study developed signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), a constellation of ocular structural and functional changes seen in approximately one third of long duration astronauts. This allowed us the unique opportunity to compare the two subgroups. We found that participants who exhibited signs of SANS became more visually dependent and shifted their speed-accuracy tradeoff, such that they were slower but more accurate than those that did not incur ocular changes. These small subgroup findings suggest that SANS may have an impact on mission relevant performance inflight via sensory reweighting.New And NoteworthyWe examined the effects of long duration head down tilt bed rest coupled with elevated CO2 as a spaceflight analog environment on human cognitive and sensorimotor performance. We found enhancements in processing speed and declines in functional mobility. A subset of participants exhibited signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), which affects approximately one in three astronauts. These individuals increased their visual reliance throughout the intervention in comparison to participants who did not show signs of SANS.

Prolonged Microgravity Affects Human Brain Structure and Function.

Widespread brain structural changes are seen following extended spaceflight missions. The purpose of this study was to investigate whether these structural changes are associated with alterations in motor or cognitive function. Brain MR imaging scans of National Aeronautics and Space Administration astronauts were retrospectively analyzed to quantify pre- to postflight changes in brain structure. Local structural changes were assessed using the Jacobian determinant. Structural changes were compared with clinical findings and cognitive and motor function. Long-duration spaceflights aboard the International Space Station, but not short-duration Space Shuttle flights, resulted in a significant increase in total ventricular volume (10.7% versus 0%, P < .001, n = 12 versus n = 7). Total ventricular volume change was significantly associated with mission duration (r = 0.72, P = .001, n = 19) but negatively associated with age (r = -0.48, P = .048, n = 19). Long-duration spaceflights resulted in significant crowding of brain parenchyma at the vertex. Pre- to postflight structural changes of the left caudate correlated significantly with poor postural control; and the right primary motor area/midcingulate correlated significantly with a complex motor task completion time. Change in volume of 3 white matter regions significantly correlated with altered reaction times on a cognitive performance task (bilateral optic radiations, splenium of the corpus callosum). In a post hoc finding, astronauts who developed spaceflight-associated neuro-ocular syndrome demonstrated smaller changes in total ventricular volume than those who did not (12.8% versus 6.5%, n = 8 versus n = 4). While cautious interpretation is appropriate given the small sample size and number of comparisons, these findings suggest that brain structural changes are associated with changes in cognitive and motor test scores and with the development of spaceflight-associated neuro-optic syndrome.

Biofluid modeling of the coupled eye-brain system and insights into simulated microgravity conditions.

This work aims at investigating the interactions between the flow of fluids in the eyes and the brain and their potential implications in structural and functional changes in the eyes of astronauts, a condition also known as spaceflight associated neuro-ocular syndrome (SANS). To this end, we propose a reduced (0-dimensional) mathematical model of fluid flow in the eyes and brain, which is embedded into a simplified whole-body circulation model. In particular, the model accounts for: (i) the flows of blood and aqueous humor in the eyes; (ii) the flows of blood, cerebrospinal fluid and interstitial fluid in the brain; and (iii) their interactions. The model is used to simulate variations in intraocular pressure, intracranial pressure and blood flow due to microgravity conditions, which are thought to be critical factors in SANS. Specifically, the model predicts that both intracranial and intraocular pressures increase in microgravity, even though their respective trends may be different. In such conditions, ocular blood flow is predicted to decrease in the choroid and ciliary body circulations, whereas retinal circulation is found to be less susceptible to microgravity-induced alterations, owing to a purely mechanical component in perfusion control associated with the venous segments. These findings indicate that the particular anatomical architecture of venous drainage in the retina may be one of the reasons why most of the SANS alterations are not observed in the retina but, rather, in other vascular beds, particularly the choroid. Thus, clinical assessment of ocular venous function may be considered as a determinant SANS factor, for which astronauts could be screened on earth and in-flight.

Gravitational Influence on Intraocular Pressure: Implications for Spaceflight and Disease.

Spaceflight-associated neuro-ocular syndrome (SANS) describes a series of morphologic and functional ocular changes in astronauts first reported by Mader and colleagues in 2011. SANS is currently clinically defined by the development of optic disc edema during prolonged exposure to the weightless (microgravity) environment, which currently occurs on International Space Station (ISS). However, as improvements in our understanding of the ocular changes emerge, the definition of SANS is expected to evolve. Other ocular SANS signs that arise during and after ISS missions include hyperopic shifts, globe flattening, choroidal/retinal folds, and cotton wool spots. Over the last 10 years, ~1 in 3 astronauts flying long-duration ISS missions have presented with ≥1 of these ocular findings. Commensurate with research that combines disparate specialties (vision biology and spaceflight medicine), lessons from SANS investigations may also yield insight into ground-based ocular disorders, such as glaucomatous optic neuropathy that may have the potential to lessen the burden of this irreversible cause of vision loss on Earth.