Reducing intracranial pressure by reducing central venous pressure: assessment of potential countermeasures to spaceflight-associated neuro-ocular syndrome

Hansen, Alexander B.; Lawley, Justin S.; Rickards, Caroline A.; Howden, Erin J.; Sarma, Satyam; Cornwell, William K.; Amin, Sachin B.; Mugele, Hendrik; Marume, Kyohei; Possnig, Carmen; Whitworth, Louis A.; Williams, Michael A.; Levine, Benjamin D.

doi:10.1152/japplphysiol.00786.2020

Cited by 12 publications

(6 citation statements)

References 23 publications

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“…Third, breathing against inspiratory resistance has also been hypothesized as a countermeasure to increased ICP and central venous pressure (CVP). Recently, a study by Hansen and colleagues, 49 using Ommaya reservoirs to measure ICP and peripherally inserted central catheters to measure CVP, showed that acute thigh cuff inflation had little effect on ICP or CVP. In contrast, impedance threshold breathing acutely reduced ICP via a reduction in CVP.…”

Section: Discussionmentioning

confidence: 99%

Does Long-Duration Exposure to Microgravity Lead to Dysregulation of the Brain and Ocular Glymphatic Systems?

Wostyn¹,

Mader²,

Gibson³

et al. 2022

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Spaceflight-associated neuro-ocular syndrome (SANS) has been well documented in astronauts both during and after long-duration spaceflight and is characterized by the development of optic disc edema, globe flattening, choroidal folds, and hyperopic refractive error shifts. The exact mechanisms underlying these ophthalmic abnormalities remain unclear. New findings regarding spaceflight-associated alterations in cerebrospinal fluid spaces, specifically perivascular spaces, may shed more light on the pathophysiology of SANS. The preliminary results of a recent brain magnetic resonance imaging study show that perivascular spaces enlarge under prolonged microgravity conditions, and that the amount of fluid in perivascular spaces is linked to SANS. The exact pathophysiological mechanisms underlying enlargement of perivascular spaces in space crews are currently unclear. Here, we speculate that the dilation of perivascular spaces observed in long-duration space travelers may result from impaired cerebral venous outflow and compromised cerebrospinal fluid resorption, leading to obstruction of glymphatic perivenous outflow and increased periarterial cerebrospinal fluid inflow, respectively. Further, we provide a possible explanation for how dilated perivascular spaces can be associated with SANS. Given that enlarged perivascular spaces in space crews may be a marker of altered venous hemodynamics and reduced cerebrospinal fluid outflow, at the level of the optic nerve and eye, these disturbances may contribute to SANS. If confirmed by further studies, brain glymphatic dysfunction in space crews could potentially be considered a risk factor for the development of neurodegenerative diseases, such as Alzheimer’s disease. Furthermore, long-duration exposure to microgravity might contribute to SANS through dysregulation of the ocular glymphatic system. If prolonged spaceflight exposure causes disruption of the glymphatic systems, this might affect the ability to conduct future exploration missions, for example, to Mars. The considerations outlined in the present paper further stress the crucial need to develop effective long-term countermeasures to mitigate SANS-related physiologic changes during long-duration spaceflight.

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Section: Discussionmentioning

confidence: 99%

Does Long-Duration Exposure to Microgravity Lead to Dysregulation of the Brain and Ocular Glymphatic Systems?

Wostyn¹,

Mader²,

Gibson³

et al. 2022

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“…As previously states, ICP differs significantly significantly upon different body position, and this discrepancy is probably mostly due to the hydrostatic pressure gradient caused by the gravitational pull. Notably, astronauts in whom gravity and thus the daily ICP variations of positional shifts are eliminated, frequently manifest symptoms associated with increased ICP, such as papilledema and headache [ 45 , 46 ]. However, a study by Lawley et al found that the absence of gravity does not increase supine ICP to pathological levels [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Intracranial pressure following surgery of an unruptured intracranial aneurysm—a model for normal intracranial pressure in humans

Norager,

Lilja-Cyron,

Riedel

et al. 2024

Fluids Barriers CNS

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Objective Optimizing the treatment of several neurosurgical and neurological disorders relies on knowledge of the intracranial pressure (ICP). However, exploration of normal ICP and intracranial pressure pulse wave amplitude (PWA) values in healthy individuals poses ethical challenges, and thus the current documentation remains scarce. This study explores ICP and PWA values for healthy adults without intracranial pathology expected to influence ICP. Methods Adult patients (age > 18 years) undergoing surgery for an unruptured intracranial aneurysm without any other neurological co-morbidities were included. Patients had a telemetric ICP sensor inserted, and ICP was measured in four different positions: supine, lateral recumbent, standing upright, and 45-degree sitting, at day 1, 14, 30, and 90 following the surgery. Results ICP in each position did not change with time after surgery. Median ICP was 6.7 mmHg and median PWA 2.1 mmHg in the supine position, while in the upright standing position median ICP was − 3.4 mmHg and median PWA was 1.9 mmHg. After standardization of the measurements from the transducer site to the external acoustic meatus, the median ICPmidbrain was 8.3 mmHg in the supine position and 1.2 mmHg in the upright standing position. Conclusion Our study provides insights into normal ICP dynamics in healthy adults following a uncomplicated surgery for an unruptured aneurysm. These results suggest a slightly wider normal reference range for invasive intracranial pressure than previously suggested, and present the first normal values for PWA in different positions. Further studies are, however, essential to enhance our understanding of normal ICP. Trial registration The study was preregistered at www.clinicaltrials.gov (NCT03594136) (11 July 2018)

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“…A fluid-filled 4F catheter was placed into a brachial vein . The catheter was advanced to the level of right atrium, and the correct position was confirmed with fluoroscopy and through the identification of CVP waveforms.…”

Section: Methodsmentioning

confidence: 99%

“…A fluid-filled 4F catheter was placed into a brachial vein. 18 The catheter was advanced to the level of right atrium, and the correct position was confirmed with fluoroscopy and through the identification of CVP waveforms. Position of the right atrium was marked on the body in the anteroposterior and lateral planes, and the pressure transducer (Transpac IV; ICU Medical) was leveled at the right atrium and zeroed to atmospheric pressure in all conditions.…”

Section: Cvpmentioning

confidence: 99%

Effect of Nightly Lower Body Negative Pressure on Choroid Engorgement in a Model of Spaceflight-Associated Neuro-ocular Syndrome

et al. 2022

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IMPORTANCE Astronauts returning from long-duration spaceflight experience ocular remodeling related to cephalad fluid shifts induced by microgravity. It is hypothesized that the absence of diurnal reductions in intracranial pressure in microgravity creates a low but persistent pressure gradient at the posterior aspect of the eye, which results in ocular remodeling and space-associated neuro-ocular syndrome (SANS) over many months.OBJECTIVE To determine whether partial reintroduction of footward fluid shifts during simulated microgravity via lower body negative pressure (LBNP) during sleep attenuates choroid engorgement, an early marker of ocular remodeling related to SANS. DESIGN, SETTING, AND PARTICIPANTSBetween May 2019 and February 2020, participants with no major cardiovascular, kidney, or ophthalmic disease completed 3 days of supine (0°) bed rest with and 3 days without 8 hours of nightly LBNP in a randomized, crossover design. This single-center investigation took place at the UT Southwestern Medical Center. All analyses were conducted blinded to condition and time point. INTERVENTIONS Eight hours of nightly LBNP (−20 mm Hg) vs no LBNP.MAIN OUTCOMES AND MEASURES The primary outcome was the change in choroid area and volume after 3 days of bed rest measured by optical coherence tomography. RESULTSOf 10 participants, 5 were female, the mean (SD) age was 29 (9) years, and the age range was 18 to 55 years. Central venous pressure increased from the seated to supine position (mean [SD], seated: −2.3 [2.0] vs supine: 6.9 [2.0] mm Hg; P < .001), leading to choroid engorgement over 3 days of bed rest (Δ area: +0.09 mm 2 [95% CI, 0.04-0.13]; P = .001; Δ volume: +0.37 mm 3 [95% CI, 0.19-0.55]; P = .001). Nightly LBNP caused a sustained reduction in supine central venous pressure (mean [SD], 5.7 [2.2] mm Hg to 1.2 [1.4 mm Hg]; P < .001) and attenuated the increase in choroid area (74%) (Δ: 0.02 mm 2 [95% −0.02 to 0.06]; P = .01) and volume (53%) (Δ: 0.17 mm 3 [95% CI, 0.01-0.34]; P = .05) compared with control.CONCLUSIONS AND RELEVANCE Nightly LBNP reinstated a footward fluid shift and mitigated the increase in choroid area and volume. LBNP during sleep may be an effective countermeasure for ocular remodeling and SANS during long-duration space missions.

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Reducing intracranial pressure by reducing central venous pressure: assessment of potential countermeasures to spaceflight-associated neuro-ocular syndrome

Cited by 12 publications

References 23 publications

Does Long-Duration Exposure to Microgravity Lead to Dysregulation of the Brain and Ocular Glymphatic Systems?

Does Long-Duration Exposure to Microgravity Lead to Dysregulation of the Brain and Ocular Glymphatic Systems?

Intracranial pressure following surgery of an unruptured intracranial aneurysm—a model for normal intracranial pressure in humans

Effect of Nightly Lower Body Negative Pressure on Choroid Engorgement in a Model of Spaceflight-Associated Neuro-ocular Syndrome

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