Case Report: No Evidence of Intracranial Fluid Shifts in an Astronaut Following an Aborted Launch

Spaceflight induces lasting enlargement of the brain's ventricles as well as intracranial fluid shifts. These intracranial fluid shifts have been attributed to prolonged microgravity exposure, however, the potential effects of hypergravity exposure during launch and landing have yet to be elucidated. Here we describe a case report of a Crewmember who experienced an Aborted Launch (“CAL”). CAL's launch and landing experience was dissociated from prolonged microgravity exposure. Using MRI, we show that hypergravity exposure during the aborted launch did not induce lasting ventricular enlargement or intracranial fluid shifts resembling those previously reported with spaceflight. This case study therefore rules out hypergravity during launch and landing as a contributing factor to previously reported long-lasting intracranial fluid changes following spaceflight.

Opposite response of blood vessels in the retina to 6° head-down tilt and long-duration microgravity

The Spaceflight Associated Neuro-ocular Syndrome (SANS), associated with the headward fluid shifts incurred in microgravity during long-duration missions, remains a high-priority health and performance risk for human space exploration. To help characterize the pathophysiology of SANS, NASA’s VESsel GENeration Analysis (VESGEN) software was used to map and quantify vascular adaptations in the retina before and after 70 days of bed rest at 6-degree Head-Down Tilt (HDT), a well-studied microgravity analog. Results were compared to the retinal vascular response of astronauts following 6-month missions to the International Space Station (ISS). By mixed effects modeling, the trends of vascular response were opposite. Vascular density decreased significantly in the 16 retinas of eight astronauts and in contrast, increased slightly in the ten retinas of five subjects after HDT (although with limited significance). The one astronaut retina diagnosed with SANS displayed the greatest vascular loss. Results suggest that microgravity is a major variable in the retinal mediation of fluid shifts that is not reproduced in this HDT bed rest model.

Overnight Rostral Fluid Shifts Exacerbate Obstructive Sleep Apnea After Stroke

Background and Purpose: Overnight shifts of fluid from lower to upper compartments exacerbate obstructive sleep apnea (OSA) in some OSA populations. Given the high prevalence of OSA after stroke, decreased mobility and use of IV fluids among hospitalized patients with stroke, and improvement in OSA in the months after stroke, we hypothesized that overnight fluid shifts occur and are associated with OSA among patients with subacute ischemic stroke. Methods: Within a population-based project, we performed overnight sleep apnea tests (ApneaLink Plus) during ischemic stroke hospitalizations. Before sleep that evening, and the following morning before rising from bed, we assessed neck and calf circumference, and leg fluid volume (bioimpedance spectroscopy). The average per subject overnight change in the 3 fluid shift measurements was calculated and compared with zero. Linear regression was used to test the crude association between each of the 3 fluid shift measurements and the respiratory event index (REI). Results: Among the 292 participants, mean REI was 24 (SD=18). Within individuals, calf circumference decreased on average by 0.66 cm (SD=0.75 cm, P <0.001), leg fluid volume decreased by a mean of 135.6 mL (SD=132.8 mL, P <0.001), and neck circumference increased by 0.20 cm (SD=1.71 cm, P =0.07). In men, when the overnight change of calf circumference was negative, an interquartile range (0.8 cm) decrease in calf circumference overnight was significantly associated with a 25.1% increase in REI ( P =0.02); the association was not significant in women. The relationship between overnight change in leg fluid volume and REI was U shaped. Conclusions: This population-based, multicenter, cross-sectional study showed that in hospitalized patients with ischemic stroke, nocturnal rostral fluid shifts occurred, and 2 of the 3 measures were associated with greater OSA severity. Interventions that limit overnight fluid shifts should be tested as potential treatments for OSA among patients with subacute ischemic stroke.

Physiological adaptations affecting drug pharmacokinetics in space: what do we really know? A critical review of the literature.

As human spaceflight continues with extended mission durations, the demand of effective and safe drugs is going to increase. To date, the medications used during missions (for space motion sickness, sleep disturbances, allergies, pain and sinus congestion) are administered under the assumption that they act similarly as on the Earth. During spaceflights however fluid shifts, muscle and bone loss, immune system dysregulation and changes in the gastrointestinal tract and metabolism are documented. These alterations may change the pharmacokinetics (PK) and pharmacodynamics. The information gained from bed-rest studies and from inflight observations is partial and demonstrates variability in drug PK. The objectives of this review are to report: i) the impact of the space environmental stressors on human physiology in relation to PK; ii) the state-of-the-art on experimental data in space and/or in ground-based models; iii) the validation of ground-based models for PK studies; and iv) the identification of possible research gaps.

Human Neural Stem Cells in Space Proliferate more than Ground Control Cells: Implications for Long-Term Space Travel

Long-term travel and lengthy stays for astronauts in outer space are imminent. To date, more than 500 astronauts have experienced the extreme conditions of space flight including microgravity and radiation. For the past decade, many studies associated with long-duration spaceflight have shown the recurring occurrence of ophthalmic abnormalities. The reasons of the observed changes in some astronauts remained unclear. However, factors such as the increase in intracranial pressure and fluid shifts are among the top potential contributing elements.

MRI-based quantification of ophthalmic changes in healthy volunteers during acute 15° head-down tilt as an analogue to microgravity

Spaceflight is known to cause ophthalmic changes in a condition known as spaceflight-associated neuro-ocular syndrome (SANS). It is hypothesized that SANS is caused by cephalad fluid shifts and potentially mild elevation of intracranial pressure (ICP) in microgravity. Head-down tilt (HDT) studies are a ground-based spaceflight analogue to create cephalad fluid shifts. Here, we developed non-invasive magnetic resonance imaging (MRI)-based techniques to quantify ophthalmic structural changes under acute 15° HDT. We specifically quantified: (i) change in optic nerve sheath (ONS) and optic nerve (ON) cross-sectional area, (ii) change in ON deviation, an indicator of ON tortuosity, (iii) change in vitreous chamber depth, and (iv) an estimated ONS Young's modulus. Under acute HDT, ONS cross-sectional area increased by 4.04 mm 2 (95% CI 2.88–5.21 mm 2 , p < 0. 000), while ON cross-sectional area remained nearly unchanged (95% CI −0.12 to 0.43 mm 2 , p = 0.271). ON deviation increased under HDT by 0.20 mm (95% CI 0.08–0.33 mm, p = 0.002). Vitreous chamber depth decreased under HDT by −0.11 mm (95% CI −0.21 to −0.03 mm, p = 0.009). ONS Young's modulus was estimated to be 85.0 kPa. We observed a significant effect of sex and BMI on ONS parameters, of interest since they are known risk factors for idiopathic intracranial hypertension. The tools developed herein will be useful for future analyses of ON changes in various conditions.

The Impact of Hindlimb Suspension on the Rat Eye: A Molecular and Histological Analysis of the Retina

The Spaceflight Associated Neuro-ocular Syndrome (SANS) is hypothesized to be associated with microgravity-induced fluid shifts. There is a need for an animal model of SANS to investigate its pathophysiology. We used the rat hindlimb suspension (HS) model to examine the relationship between the assumed cephalad fluid shifts, intraocular (IOP) pressure and the molecular responses in the retina to the prolonged change in body posture. Long evans rats were subjected to HS up to 90 days. Animals completing 90-day suspension were further studied for recovery periods up to 90 additional days in normal posture. With respect to baseline, the average IOP increase in HS animals and the rate of change varied by cohort. Transcriptomics evidence supported a response to HS in the rat retina that was affected by age and sex. Several molecular networks suggested stress imposed by HS affected the retinal vasculature, oxidative and inflammation status, pigmented epithelium and glia. The CSNK1A1-TP53 pathway was implicated in the response in all cohorts. Sex-specific genes were involved in cytoprotection and may explain sex-dependent vulnerabilities to certain eye diseases. These results support the hypothesis that changes in the biology of the retina subjected to simulated microgravity involve both the neural and vascular retina.