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The microgravity ocular syndrome (MOS) results in significant structural and functional ophthalmic changes during 6-mo spaceflight missions consistent with an increase in cerebrospinal fluid (CSF) pressure compared with the preflight upright position. A ground-based study was performed to assess two of the major hypothesized contributors to MOS, headward fluid shifting and increased ambient CO, on intracranial and periorbital CSF. In addition, lower body negative pressure (LBNP) was assessed as a countermeasure to headward fluid shifting. Nine healthy male subjects participated in a crossover design study with five head-down tilt (HDT) conditions: -6, -12, and -18° HDT, -12° HDT with -20 mmHg LBNP, and -12° HDT with a 1% CO environment, each for 5 h total. A three-dimensional volumetric scan of the cranium and transverse slices of the orbita were collected with MRI, and intracranial CSF volume and optic nerve sheath diameter (ONSD) were measured after 4.5 h HDT. ONSD increased during -6° ( < 0.001), -12° ( < 0.001), and -18° HDT ( < 0.001) and intracranial CSF increased during -12° HDT ( = 0.01) compared with supine baseline. Notably, LBNP was able to reduce the increases in ONSD and intracranial CSF during HDT. The addition of 1% CO during HDT, however, had no further effect on ONSD, but rather ONSD increased from baseline in a similar magnitude to -12° HDT with ambient air ( = 0.001). These findings demonstrate the ability of LBNP, a technique that targets fluid distribution in the lower limbs, to directly influence CSF and may be a promising countermeasure to help reduce increases in CSF. This is the first study to demonstrate the ability of lower body negative pressure to directly influence cerebrospinal fluid surrounding the optic nerve, indicating potential use as a countermeasure for increased cerebrospinal fluid on Earth or in space.

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