The visual impairment observed in many astronauts after long duration spaceflight aboard the International Space Station is considered the most important mission threatening medical problem identified in the last decade of the space program. Between 2012 and 2014, NASA and NSBRI spent $3-4 million/year investigating the clinical course and underlying mechanisms of this condition, termed the Visual Impairment Intracranial Pressure syndrome (VIIP) because of its theoretical association with elevated intracranial pressure (ICP). During recently completed experiments funded by NSBRI, the investigators for this application performed the first invasive measures of intracranial pressure during acute (head down tilt bedrest, and parabolic flight) and chronic (24 hours HDT bedrest) changes in gravitational gradients simulating spaceflight in healthy humans and have made the following novel observations: 1) there is a large range of ICP experienced normally during changes in posture in daily life; 2) these changes occur within seconds of postural transients from upright to supine and then are stable over time in that position; 3) with acute assumption of simulated microgravity (HDT bedrest), ICP goes up slightly from the supine position, but over the next 24 hours, returns towards, and sometimes below the supine value because of spatial compensation within the brain; 4) during true microgravity (parabolic flight), the acute reduction in central venous pressure reduces cerebral outflow resistance and ICP decreases compared to the supine position, though remains above the upright position in 1G. Together, these results have led us to hypothesize that the VIIP syndrome is NOT due to a pathologically elevated ICP. However because there is not the usual reduction in ICP typically seen in the upright position on earth, the incessant, low level elevation in ICP (i.e., greater than upright, but less than supine) leads to adaptive changes in the eye which ultimately result in globe flattening, choroidal folds, and visual impairment.
This project will provide novel data about the efficacy of lower body negative pressure to mimic daily upright posture by intermittently lowering directly measured intracranial pressure (ICP) while in simulated microgravity. Examination of the associated inflow and outflow hemodynamics, accompanied by detailed assessment of localized intracranial fluid shifts and structural changes in the visual apparatus will establish the long-term safety and feasibility of this approach. This information is essential to establishing an appropriate method to simulate the upright posture and normal circadian variability in ICP over prolonged periods of time, with the objective of providing a robust countermeasure for visual impairment in astronauts.