Spaceflight-Associated Neuro-Ocular Syndrome (SANS) is considered an unexplained major risk for future long-duration spaceflight. Evidence thus reviewed supports that chronic, mildly elevated intracranial pressure (ICP) in space (as opposed to more variable ICP with posture and activity on Earth) is largely accounted for by loss of hydrostatic pressures and altered hemodynamics in the intracranial circulation and the cerebrospinal fluid system.
In space, an elevated pressure gradient across the lamina cribrosa, caused by a chronic but mildly-elevated ICP, likely elicits adaptations of multiple structures and fluid systems, which manifest themselves as SANS in the neurologic and ocular systems. A chronic mismatch between ICP and intraocular pressure (IOP) in space may alter the optic nerve head, lamina cribrosa and optic nerve subarachnoid space in a manner that is maladaptive to Earth and contributes to the pathogenesis of SANS.
This study including parabolic-flight tests will be supported by MRI studies to investigate cranial and neck blood volumes and flows along with cerebral compliance in response to simulated weightlessness and self-generated lower body negative pressure (LBNP). The long-term goal is to understand and optimize the LBNP level and dose (dose = time of application per day and days of use per week) of self-generated LBNP to help maintain the health of crewmembers. Moreover, the studies of Starling forces (tissue pressures during short-term, actual microgravity by parabolic flight) will improve the understanding of mechanisms and contributing risk factors for ocular structural and functional changes seen in-flight during deep-space missions.
The goal of this research is to: (1) elucidate how the interplay between and alleviation of increased intraocular pressure, intracranial pressure, and venous congestion alter the development of SANS, and (2) determine the dosing and effectiveness of a novel, Self-Generated and Exercise Powered LBNP device to reproduce daily, Earth-like postures and activities in order to prevent cephalad fluid shifts and SANS development. This novel LBNP device generates a negative pressure gradient across the lower body when it is expanded and contracted with exercise. The investigator team’s next-generation device includes hardware that stores the mechanical energy transferred to the device from exercise in order to power the LBNP at a later time without physical exertion. This device is unique in that it is integrated with exercise, requires no power to run, stores mechanical energy, and allows LBNP generation in an active or passive manner.
This study has the following specific aims:
1) Determine the immediate effects of pulsatile, self-generated LBNP on cardiovascular, cerebral and ocular systems.
2) Characterize the intermediate timescale responses in a SANS microgravity model, and determine dose-response relationship of the self-generated LBNP device as a countermeasure for SANS.
3) Extend Aims 1 and 2 studies of ICP and cerebral perfusion during acute periods of actual microgravity provided by parabolic flight to understand mechanisms of SANS and apply the self-generated LBNP device to reverse the cephalic fluid shift.
Investigators will test 12 healthy female and male subjects in a repeated measures design with 30 minutes of supine posture, 30 minutes to 1 hour of active, self-generated LBNP, and up to four hours of exercise powered, passive LBNP.
This research will start with mapping out immediate effects of Self-Generated LBNP on cardiovascular, ocular, and cerebral physiology (Aim 1). This will later extend to a three-day, supine, cross-over bed rest study to see if the investigators can determine the dose of self-generated LBNP required to reproduce the beneficial effects of eight-hours conventional LBNP on reducing edema at the back of the eye (Aim 2). Finally, in year 3, the investigators hypothesize that actual microgravity by parabolic flights will confirm that Self-Generated LBNP has beneficial venous, cerebral, and ocular ACUTE effects for SANS prevention (Aim 3).
This integrated countermeasure of self-generated LBNP may make return to gravity easier and reduce postflight recovery. The self-generated LBNP device is very timely with NASA’s need to provide an integrated countermeasure for SANS and musculoskeletal atrophy, while at the same time providing a physiologically-integrated exercise device that is safe, low mass, low volume, human powered and simple for deployment in a confined deep space vehicle. It is also anticipated that the self-generated LBNP device for 30 minutes to 1 hour of exercise and up to 4 hours passively during three days of simulated microgravity will prevent venous congestion, elevated intraocular pressure (IOP), increased intracranial pressure, and cerebral edema formation. This will all help maintain higher intracranial compliance.
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