Inspiration is the major regulator of human CSF flow.

The mechanisms behind CSF flow in humans are still not fully known. CSF circulates from its primary production sites at the choroid plexus through the brain ventricles to reach the outer surface of the brain in the subarachnoid spaces from where it drains into venous bloodstream and cervical lymphatics. According to a recent concept of brain fluid transport, established in rodents, CSF from the brain surface also enters the brain tissue along para-arterial routes and exits through paravenous spaces again into subarachnoid compartments. This unidirectional flow is mainly driven by arterial pulsation. To investigate how CSF flow is regulated in humans, we applied a novel real-time magnetic resonance imaging technique at high spatial (0.75 mm) and temporal (50 ms) resolution in healthy human subjects. We observed significant CSF flow exclusively with inspiration. In particular, during forced breathing, high CSF flow was elicited during every inspiration, whereas breath holding suppressed it. Only a minor flow component could be ascribed to cardiac pulsation. The present results unambiguously identify inspiration as the most important driving force for CSF flow in humans. Inspiratory thoracic pressure reduction is expected to directly modulate the hydrostatic pressure conditions for the low-resistance paravenous, venous, and lymphatic clearance routes of CSF. Furthermore, the experimental approach opens new clinical opportunities to study the pathophysiology of various forms of hydrocephalus and to design therapeutic strategies in relation to CSF flow alterations

Identification of the upward movement of human CSF in vivo and its relation to the brain venous system.

CSF flux is involved in the pathophysiology of neurodegenerative diseases and cognitive impairment after traumatic brain injury, all hallmarked by the accumulation of cellular metabolic waste. Its effective disposal via various CSF routes has been demonstrated in animal models. In contrast, the CSF dynamics in humans are still poorly understood. Using novel real-time MRI, forced inspiration has been identified recently as a main driving force of CSF flow in the human brain. Exploiting technical advances toward real-time phase-contrast MRI, the current work analyzed directions, velocities, and volumes of human CSF flow within the brain aqueduct as part of the internal ventricular system and in the spinal canal during respiratory cycles. A consistent upward CSF movement toward the brain in response to forced inspiration was seen in all subjects at the aqueduct, in 11/12 subjects at thoracic level 2, and in 4/12 subjects at thoracic level 5. Concomitant analyses of CSF dynamics and cerebral venous blood flow, that is, in epidural veins at cervical level 3, uniquely demonstrated CSF and venous flow to be closely communicating cerebral fluid systems in which inspiration-induced downward flow of venous blood due to reduced intrathoracic pressure is counterbalanced by an upward movement of CSF. The results extend our understanding of human CSF flux and open important clinical implications, including concepts for drug delivery and new classifications and therapeutic options for various forms of hydrocephalus and idiopathic intracranial hypertension

Deep breathing couples CSF and venous flow dynamics

Venous system pathologies have increasingly been linked to clinically relevant disorders of CSF circulation whereas the exact coupling mechanisms still remain unknown. In this work, flow dynamics of both systems were studied using real-time phase-contrast flow MRI in 16 healthy subjects during normal and forced breathing. Flow evaluations in the aqueduct, at cervical level C3 and lumbar level L3 for both the CSF and venous fluid systems reveal temporal modulations by forced respiration. During normal breathing cardiac-related flow modulations prevailed, while forced breathing shifted the dominant frequency of both CSF and venous flow spectra towards the respiratory component and prompted a correlation between CSF and venous flow in the large vessels. The average of flow magnitude of CSF was increased during forced breathing at all spinal and intracranial positions. Venous flow in the large vessels of the upper body decreased and in the lower body increased during forced breathing. Deep respiration couples interdependent venous and brain fluid flow—most likely mediated by intrathoracic and intraabdominal pressure changes. Further insights into the driving forces of CSF and venous circulation and their correlation will facilitate our understanding how the venous system links to intracranial pressure regulation and of related forms of hydrocephalus

The rovibrational spectrum of BeH, MgH and CaH at high temperatures in the X 2Σ+X\,{}^2\Sigma^+ state: a theoretical study

Accurate line lists for three molecules, BeH, MgH and CaH, in their ground electronic states are presented. These line lists are suitable for temperatures relevant to exoplanetary atmospheres and cool stars (up to 2000K). A combination of empirical and \textit{ab initio} methods is used. The rovibrational energy levels of BeH, MgH and CaH are computed using the programs Level and DPotFit in conjunction with `spectroscopic' potential energy curves (PECs). The PEC of BeH is taken from the literature, while the PECs of CaH and MgH are generated by fitting to the experimental transition energy levels. Both spin-rotation interactions (except for BeH, for which it is negligible) and non-adiabatic corrections are explicitly taken into account. Accurate line intensities are generated using newly computed \textit{ab initio} dipole moment curves for each molecule using high levels of theory. Full line lists of rotation-vibration transitions for $^9$BeH, $^{24}$MgH, $^{25}$MgH, $^{26}$MgH and $^{40}$CaH are made available in an electronic form as supplementary data to this article and at \url{www.exomol.com}.Comment: MNRAS (in press

Sleep Is Compromised in −12° Head Down Tilt Position

Recent studies are elucidating the interrelation between sleep, cranial perfusion, and cerebrospinal fluid (CSF) circulation. Head down tilt (HDT) as a simulation of microgravity reduces cranial perfusion. Therefore, our aim was to assess whether HDT is affecting sleep (clinicaltrials.gov; identifier NCT 02976168). 11 male subjects were recruited for a cross-over designed study. Each subject participated in two campaigns each comprising 3 days and 2 nights. Intervention started on the second campaign day and consisted of maintenance of horizontal position or −12° HDT for 21 h. Ultrasound measurements were performed before, at the beginning and the end of intervention. Polysomnographic measurements were assessed in the second night which was either spent in horizontal posture or at −12° HDT. Endpoints were sleep efficiency, sleep onset latency, number of sleep state changes and arousals, percentages of N3, REM, light sleep stages and subjective sleep parameters. N3 and REM sleep reduced by 25.6 and 19.1 min, respectively (P = 0.002, g = -0.898; P = 0.035, g = -0.634) during −12° HDT. Light sleep (N1/2) increased by 33.0 min at −12° HDT (P = 0.002, g = 1.078). On a scale from 1 to 9 subjective sleep quality deteriorated by 1.3 points during −12° HDT (P = 0.047, g = -0.968). Ultrasonic measurement of the venous system showed a significant increase of the minimum (P = 0.009, P < 0.001) and maximum (P = 0.004, P = 0.002) cross-sectional area of the internal jugular vein at −12° HDT. The minimum cross-sectional area of the external jugular vein differed significantly between conditions over time (P = 0.001) whereas frontal skin tissue thickness was not significantly different between conditions (P = 0.077, P = 0.811). Data suggests venous congestion at −12° HDT. Since subjects felt comfortable with lying in −12° HDT under our experimental conditions, this posture only moderately deteriorates sleep. Obviously, the human body can almost compensate the several fold effects of gravity in HDT posture like an affected CSF circulation, airway obstruction, unusual patterns of propioception and effects on the cardiovascular system