Noninvasive indicators of intracranial pressure before, during, and after long-duration spaceflight.

Weightlessness induces a cephalad shift of blood and cerebrospinal fluid that may increase intracranial pressure (ICP) during spaceflight, whereas lower body negative pressure (LBNP) may provide an opportunity to caudally redistribute fluids and lower ICP. To investigate the effects of spaceflight and LBNP on noninvasive indicators of ICP (nICP), we studied 13 crewmembers before and after spaceflight in seated, supine, and 15° head-down tilt postures, and at ∼45 and ∼150 days of spaceflight with and without 25 mmHg LBNP. We used four techniques to quantify nICP: cerebral and cochlear fluid pressure (CCFP), otoacoustic emissions (OAE), ultrasound measures of optic nerve sheath diameter (ONSD), and ultrasound-based internal jugular vein pressure (IJVp). On flight day 45, two nICP measures were lower than preflight supine posture [CCFP: mean difference -98.5 -nL (CI: -190.8 to -6.1 -nL), P = 0.037]; [OAE: -19.7° (CI: -10.4° to -29.1°), P < 0.001], but not significantly different from preflight seated measures. Conversely, ONSD was not different than any preflight posture, whereas IJVp was significantly greater than preflight seated measures [14.3 mmHg (CI: 10.1 to 18.5 mmHg), P < 0.001], but not significantly different than preflight supine measures. During spaceflight, acute LBNP application did not cause a significant change in nICP indicators. These data suggest that during spaceflight, nICP is not elevated above values observed in the seated posture on Earth. Invasive measures would be needed to provide absolute ICP values and more precise indications of ICP change during various phases of spaceflight.NEW & NOTEWORTHY The current study provides new evidence that intracranial pressure (ICP), as assessed with noninvasive measures, may not be elevated during long-duration spaceflight. In addition, the acute use of lower body negative pressure did not significantly reduce indicators of ICP during weightlessness.

Mechanical countermeasures to headward fluid shifts.

Head-to-foot gravitationally induced hydrostatic pressure gradients in the upright posture on Earth are absent in weightlessness. This results in a relative headward fluid shift in the vascular and cerebrospinal fluid compartments and may underlie multiple physiological consequences of spaceflight, including the spaceflight-associated neuro-ocular syndrome. Here, we tested three mechanical countermeasures [lower body negative pressure (LBNP), venoconstrictive thigh cuffs (VTC), and impedance threshold device (ITD) resistive inspiratory breathing] individually and in combination to reduce a posture-induced headward fluid shift as a ground-based spaceflight analog. Ten healthy subjects (5 male) underwent baseline measures (seated and supine postures) followed by countermeasure exposure in the supine posture. Noninvasive measurements included ultrasound [internal jugular veins (IJV) cross-sectional area, cardiac stroke volume, optic nerve sheath diameter, noninvasive IJV pressure], transient evoked otoacoustic emissions (OAE; intracranial pressure index), intraocular pressure, choroidal thickness from optical coherence tomography imaging, and brachial blood pressure. Compared with the supine posture, IJV area decreased 48% with application of LBNP [mean ratio: 0.52, 95% confidence interval (CI): 0.44-0.60, P < 0.001], 31% with VTC (mean ratio: 0.69, 95% CI: 0.55-0.87, P < 0.001), and 56% with ITD (mean ratio: 0.44, 95% CI: 0.12-1.70, P = 0.46), measured at end-inspiration. LBNP was the only individual countermeasure to decrease the OAE phase angle (Δ -12.9 degrees, 95% CI: -25 to -0.9, P = 0.027), and use of combined countermeasures did not result in greater effects. Thus, LBNP, and to a lesser extent VTC and ITD, represents promising headward fluid shift countermeasures but will require future testing in analog and spaceflight environments.NEW & NOTEWORTHY As a weightlessness-induced headward fluid shift is hypothesized to be a primary factor underlying several physiological consequences of spaceflight, countermeasures aimed at reversing the fluid shift will likely be crucial during exploration-class spaceflight missions. Here, we tested three mechanical countermeasures individually and in various combinations to reduce a posture-induced headward fluid shift as a ground-based spaceflight analog.

Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates.

The evolutionarily conserved planar cell polarity (PCP) pathway (or noncanonical Wnt pathway) drives several important cellular processes, including epithelial cell polarization, cell migration and mitotic spindle orientation. In vertebrates, PCP genes have a vital role in polarized convergent extension movements during gastrulation and neurulation. Here we show that mice with mutations in genes involved in Bardet-Biedl syndrome (BBS), a disorder associated with ciliary dysfunction, share phenotypes with PCP mutants including open eyelids, neural tube defects and disrupted cochlear stereociliary bundles. Furthermore, we identify genetic interactions between BBS genes and a PCP gene in both mouse (Ltap, also called Vangl2) and zebrafish (vangl2). In zebrafish, the augmented phenotype results from enhanced defective convergent extension movements. We also show that Vangl2 localizes to the basal body and axoneme of ciliated cells, a pattern reminiscent of that of the BBS proteins. These data suggest that cilia are intrinsically involved in PCP processes.

Otoacoustic emissions, their origin in cochlear function, and use.

Otoacoustic emissions (OAEs) are sounds of cochlear origin, which can be recorded by a microphone fitted into the ear canal. They are caused by the motion of the cochlea's sensory hair cells as they energetically respond to auditory stimulation. OAEs provide a simple, efficient and non-invasive objective indicator of healthy cochlear function and OAE screening is widely used in universal new-born hearing screening programmes. As part of the audiological diagnostic test battery, OAEs can contribute to differential audiological diagnosis, they can be used to monitor the effects of treatment and they can be helpful in the selection of hearing aids and of surgical options. As a research tool, OAEs provide a non-invasive window on intracochlear processes and this has led to new insights into the mechanisms and function of the cochlea and also to a new understanding of the nature of sensory hearing impairment. This chapter provides a broad introduction to OAEs and their applications together with a detailed description of the relationship between OAEs and cochlear mechanisms.