Acute Gravitational Stress Selectively Impairs Dynamic Cerebrovascular Reactivity in the Anterior Circulation Independent of Changes to the Central Respiratory Chemoreflex

Cerebrovascular reactivity (CVR) to changes in the partial pressure of arterial carbon dioxide (PaCO2) is an important mechanism that maintains CO2 or pH homeostasis in the brain. To what extent this is influenced by gravitational stress and corresponding implications for the regulation of cerebral blood flow (CBF) remain unclear. The present study examined the onset responses of pulmonary ventilation (V̇E) and anterior middle (MCA) and posterior (PCA) cerebral artery mean blood velocity (Vmean) responses to acute hypercapnia (5% CO2) to infer dynamic changes in the central respiratory chemoreflex and cerebrovascular reactivity (CVR), in supine and 50° head-up tilt (HUT) positions. Each onset response was evaluated using a single-exponential regression model consisting of the response time latency [CO2-response delay (t0)] and time constant (τ). Onset response of V̇E and PCA Vmean to changes in CO2 was unchanged during 50° HUT compared with supine (τ: V̇E, p = 0.707; PCA Vmean, p = 0.071 vs. supine) but the MCA Vmean onset response was faster during supine than during 50° HUT (τ: p = 0.003 vs. supine). These data indicate that gravitational stress selectively impaired dynamic CVR in the anterior cerebral circulation, whereas the posterior circulation was preserved, independent of any changes to the central respiratory chemoreflex. Collectively, our findings highlight the regional heterogeneity underlying CBF regulation that may have translational implications for the microgravity (and hypercapnia) associated with deep-space flight notwithstanding terrestrial orthostatic diseases that have been linked to accelerated cognitive decline and neurodegeneration.

Seismic Anisotropy at the Hikurangi Subduction Margin

<p>To determine the stress state in the southern North Island of New Zealand, we use shear wave splitting analysis to measure seismic anisotropy and infer the orientation of the maximum horizontal stress directions (Shmax) in the crust. We use data recorded by 44 temporary seismometers deployed as part of the Seismic Array Hikurangi Experiment, and from six permanent stations from the national GeoNet network. Using 425 local earthquake events recorded across the 50 stations we made 13,807 measurements of the two splitting parameters, φ (fast direction) and δt (delay time). These measurements are compared to SHmax directions obtained from previous focal mechanism studies (SfocalHmax), and stresses due to the weight of topography (SgravHmax). Generally there is good agreement between the alignment of SfocalHmax, SgravHmax, and the mean φ measured at each station. We also find a∼ 90◦ change in the trend of φ in the Wairarapa region for stations across the Wairarapa Fault trace. Based on the variation of φ, we divide the study region into three regions (West, Basin, and East), whose bounds approximately coincide with the Wairarapa and Dry Creek faults. We find the average φ of the West region average agrees with previous anisotropy studies, which were undertaken within the bounds of the West region on the Tararua array. Also, we use our delay time measurements to estimate a 3.7±1.2% strength of anisotropy in the overriding Australian Plate, which agrees with the 4% crustal anisotropy measured previously. There is close alignment of the region average φ of the West and East regions, which also agrees with the deep splitting measurements previously obtained. There is no significant difference between the mean φ and Sgravhmax for the West and Basin regions; however, we find a difference of 31± 19.5◦ for the East region. We argue that this difference is due to tectonic loading stresses being sufficiently large in the East region to cause the total stress field to deviate from the gravitational stress field.</p>

Seismic Anisotropy at the Hikurangi Subduction Margin

<p>To determine the stress state in the southern North Island of New Zealand, we use shear wave splitting analysis to measure seismic anisotropy and infer the orientation of the maximum horizontal stress directions (Shmax) in the crust. We use data recorded by 44 temporary seismometers deployed as part of the Seismic Array Hikurangi Experiment, and from six permanent stations from the national GeoNet network. Using 425 local earthquake events recorded across the 50 stations we made 13,807 measurements of the two splitting parameters, φ (fast direction) and δt (delay time). These measurements are compared to SHmax directions obtained from previous focal mechanism studies (SfocalHmax), and stresses due to the weight of topography (SgravHmax). Generally there is good agreement between the alignment of SfocalHmax, SgravHmax, and the mean φ measured at each station. We also find a∼ 90◦ change in the trend of φ in the Wairarapa region for stations across the Wairarapa Fault trace. Based on the variation of φ, we divide the study region into three regions (West, Basin, and East), whose bounds approximately coincide with the Wairarapa and Dry Creek faults. We find the average φ of the West region average agrees with previous anisotropy studies, which were undertaken within the bounds of the West region on the Tararua array. Also, we use our delay time measurements to estimate a 3.7±1.2% strength of anisotropy in the overriding Australian Plate, which agrees with the 4% crustal anisotropy measured previously. There is close alignment of the region average φ of the West and East regions, which also agrees with the deep splitting measurements previously obtained. There is no significant difference between the mean φ and Sgravhmax for the West and Basin regions; however, we find a difference of 31± 19.5◦ for the East region. We argue that this difference is due to tectonic loading stresses being sufficiently large in the East region to cause the total stress field to deviate from the gravitational stress field.</p>

Gravitational effects on ocular pressure and perfusion pressure

Changes in the gravitational vector by postural changes or weightlessness induce fluid shifts impacting ocular hemodynamics and regional pressures. This investigation explores the impact of changes in direction of the gravitational vector on intraocular pressure (IOP), mean arterial pressure at eyelevel (MAPeye), and ocular perfusion pressure (OPP), which is critical for ocular health. Thirteen subjects underwent 360° of tilt (including both prone and supine positions) at 15º increments. At each angle, steady-state IOP and MAPeye were measured and OPP calculated as MAPeye-IOP. Experimental data were compared to a 6-compartment lumped parameter model of the eye. Mean IOP, MAPeye, and OPP significantly increased from 0º supine to 90º head down tilt (HDT) by 20.7±1.7 mmHg (ᵅD; < 0.001), 38.5±4.1 mmHg (ᵅD; < 0.001), and 17.4±3.2 mmHg (ᵅD; <0.001), respectively. Head up tilt (HUT) significantly decreased OPP by 16.5±2.5 mmHg (ᵅD; < 0.001). IOP was significantly higher in prone vs. supine position for much of the tilt range. Our study indicates that OPP is highly gravitationally dependent. Specifically, data show that MAPeye is more gravitationally dependent than IOP, thus causing OPP to increase during HDT and to decrease during HUT. Additionally, IOP was elevated in prone position compared to supine position due to the additional hydrostatic column between the base of the rostral globe to the mid-caudal plane, supporting the notion that hydrostatic forces play an important role in ocular hemodynamics. Changes in OPP as a function of changes in gravitational stress and/or weightlessness may play a role in the pathogenesis of spaceflight-associated neuro-ocular syndrome.

Modeling individual differences in cardiovascular response to gravitational stress using a sensitivity analysis

The human cardiovascular (CV) system elicits a physiological response to gravitational environments, with significant variation between different individuals. Computational modeling can predict CV response, however model complexity and variation of physiological parameters in a normal population makes it challenging to capture individual responses. We conducted a sensitivity analysis on an existing 21-compartment lumped-parameter hemodynamic model in a range of gravitational conditions to 1) investigate the influence of model parameters on a tilt test CV response and 2) to determine the subset of those parameters with the most influence on systemic physiological outcomes. A supine virtual subject was tilted to upright under the influence of a constant gravitational field ranging from 0g to 1g. The sensitivity analysis was conducted using a Latin Hypercube Sampling/Partial Rank Correlation Coefficient methodology with subsets of model parameters varied across a normal physiological range. Sensitivity was determined by variation in outcome measures including heart rate, stroke volume, central venous pressure, systemic blood pressures, and cardiac output. Results showed that model parameters related to the length, resistance, and compliance of the large veins and parameters related to right ventricular function have the most influence on model outcomes. For most outcome measures considered, parameters related to the heart are dominant. Results highlight which model parameters to accurately value in simulations of individual subjects' CV response to gravitational stress, improving the accuracy of predictions. Influential parameters remain largely similar across gravity levels, highlighting that accurate model fitting in 1g can increase the accuracy of predictive responses in reduced gravity.

A two-step gravitational cascade for the fragmentation of self-gravitating disks

Self-gravitating disks are believed to play an important role in astrophysics in particular regarding the star and planet formation process. In this context, disks subject to an idealized cooling process, characterized by a cooling timescale β expressed in unit of orbital timescale, have been extensively studied. We take advantage of the Riemann solver and the 3D Godunov scheme implemented in the code Ramses to perform high resolution simulations, complementing previous studies that have used Smoothed Particle Hydrodynamics (SPH) or 2D grid codes. We observe that the critical value of β for which the disk fragments is consistent with most previous results, and is not well converged with resolution. By studying the probability density function of the fluctuations of the column density (∑-PDF), we argue that there is no strict separation between the fragmented and the unfragmented regimes but rather a smooth transition with the probability of apparition of fragments steadily diminishing as the cooling becames less effective. We find that the high column density part of the ∑-PDF follows a simple power law whose slope turns out to be proportional to β and we propose an explanation based on the balance between cooling and heating through gravitational stress. Our explanation suggests that a more efficient cooling requires more heating implying a larger fraction of dense material which, in the absence of characteristic scales, results in a shallower scale-free power law. We propose that the gravitational cascade proceeds in two steps, first the formation of a dense filamentary spiral pattern through a sequence of quasi-static equilibrium triggered by the viscous transport of angular momentum, and second the collapse alongside these filaments that eventually results in the formation of bounded fragments.

Peripheral Blood and Salivary Biomarkers of Blood–Brain Barrier Permeability and Neuronal Damage: Clinical and Applied Concepts

Within the neurovascular unit (NVU), the blood–brain barrier (BBB) operates as a key cerebrovascular interface, dynamically insulating the brain parenchyma from peripheral blood and compartments. Increased BBB permeability is clinically relevant for at least two reasons: it actively participates to the etiology of central nervous system (CNS) diseases, and it enables the diagnosis of neurological disorders based on the detection of CNS molecules in peripheral body fluids. In pathological conditions, a suite of glial, neuronal, and pericyte biomarkers can exit the brain reaching the peripheral blood and, after a process of filtration, may also appear in saliva or urine according to varying temporal trajectories. Here, we specifically examine the evidence in favor of or against the use of protein biomarkers of NVU damage and BBB permeability in traumatic head injury, including sport (sub)concussive impacts, seizure disorders, and neurodegenerative processes such as Alzheimer's disease. We further extend this analysis by focusing on the correlates of human extreme physiology applied to the NVU and its biomarkers. To this end, we report NVU changes after prolonged exercise, freediving, and gravitational stress, focusing on the presence of peripheral biomarkers in these conditions. The development of a biomarker toolkit will enable minimally invasive routines for the assessment of brain health in a broad spectrum of clinical, emergency, and sport settings.

Reviving lower body negative pressure as a countermeasure to prevent pathological vascular and ocular changes in microgravity

Mitigation of spaceflight-related pathologies such as spaceflight-associated neuro-ocular syndrome (SANS) and the recently discovered risk of venous thrombosis must happen before deep space exploration can occur. Lower body negative pressure (LBNP) can simulate gravitational stress during spaceflight that is likely to counteract SANS and venous thrombosis, but the ideal dose and method of delivery have yet to be determined. We undertook a review of current LBNP literature and conducted a gap analysis to determine the steps needed to adapt LBNP for in-flight use. We found that to use LBNP in flight, it must be adapted to long time duration/low pressure use that should be compatible with crew activities. A lack of understanding of the etiology of the pathologies that LBNP can counteract hinders the application of LBNP as a countermeasure during spaceflight. Future research should aim at filling the knowledge gaps outlined in this review.