Sagirov et al.
Journal of Physiological Anthropology(2023) 42:5
https://doi.org/10.1186/s40101-023-00323-6

Journal of
Physiological Anthropology

Open Access

REVIEW

Postural influence on intracranial fluid
dynamics: an overview
Arlan Faritovich Sagirov1* , Timofey Vladimirovich Sergeev1, Aleksandr Vladimirovich Shabrov1,
Andrey Yur’evich Yurov1, Nadezhda Leonidovna Guseva1 and Elizaveta Aleksandrovna Agapova1

Abstract
This review focuses on the effects of different body positions on intracranial fluid dynamics, including cerebral arterial
and venous flow, cerebrospinal fluid (CSF) hydrodynamics, and intracranial pressure (ICP). It also discusses researchmethods used to quantify these effects. Specifically, the implications of three types of body positions (orthostatic,supine, and antiorthostatic) on cerebral blood flow, venous outflow, and CSF circulation are explored, with a particular emphasis on cerebrovascular autoregulation during microgravity and head-down tilt (HDT), as well as posturedependent changes in cerebral venous and CSF flow, ICP, and intracranial compliance (ICC). The review aims toprovide a comprehensive analysis of intracranial fluid dynamics during different body positions, with the potential toenhance our understanding of intracranial and craniospinal physiology.
Keywords Postural changes, Craniospinal system, Brain blood flow, Intracranial pressure, Intracranial compliance,
Cerebral autoregulation, Cerebrospinal fluid, Head-up tilt, Head-down tilt
Background
During a passive shift in body position from verticalto horizontal, various physiological processes occur,
including the redistribution of the blood in vessels andcerebrospinal fluid (CSF) in subarachnoid spaces andventricles, heart deceleration, decrease in blood pressure, adaptive reactions from the autonomic nervous
system, and changes in impulse patterns from muscle
proprioceptors and vestibular apparatus. Anthropologically, these changes are of particular interest in studying human adaptive capabilities in environments withdifferent degrees of gravitational force, while medically,
they provide an opportunity to learn more about pathological instances resulting from dysregulation of normal*Correspondence:
Arlan Faritovich Sagirov
arlansagirov@gmail.com
1
Department of Ecological Physiology, Federal State Budgetary Scientific
Institution “Institute of Experimental Medicine”, 12 Academic Pavlov St,
Saint‑Petersburg 197022, Russia

adaptive mechanisms or preexisting maladaptation. The
implications of exposure to different degrees of gravity
on the human organism have been a main focus in spacebiology and medicine. Although several studies haveextensively researched intracranial hydrodynamic shifts
and the development of orthostatic hypotension during
prolonged space flights [1–3], human body reactions topostural changes in the context of nervous and cardiovascular diseases, such as arterial hypotension, hydrocephalus, and high intracranial pressure of various causes, arenot extensively studied.
Postural changes, mostly orthostatic ones, were examined in hemodynamic and hydrodynamic aspects bydirect pressure measurement inside CSF spaces of the
craniospinal axis, Doppler ultrasonography, and MRI.
Antiorthostatic tests or head-down tilts are limited bystudies aimed at simulating environmental features, suchas microgravity and weightlessness, to learn their impact
on the human body. Nonetheless, the results and conclusions obtained from these trials can be applied to a variety of cases, such as the assessment of autoregulation of© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which
permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to theoriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images orother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
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Sagirov et al. Journal of Physiological Anthropology(2023) 42:5

cardiovascular and cerebral hemodynamics and theirinfluence on CSF circulation and brain activity, exploration of pathological conditions related to elevated intracranial pressure (ICP), and potential practical value in thecomplex application of ortho- and antiorthostatic tests
for diagnostics and rehabilitation or adaptation to spaceconditions.
This review focuses on studies that describe the flow
dynamics of blood and CSF in the brain during various
types of body positions, with a detailed look at methodological approaches used in those studies that enhanced
the quality of the results. Throughout the review, the evidence that touches upon the interrelations between CSF
flow and arterial and venous blood flow, as well as theirrespective volumes, is discussed. In the conclusion part,a hypothesized model of their flow and volume dynamics
during various postural tilts is introduced.
The objective of this review is to collect and introduce
data from several scientific works dedicated to matters inintracranial and craniospinal physiology and the postural
impact of different body tilts on CSF flow, cerebral arterial (CaBF) and venous blood flow (CvBF), ICP, intracranial compliance (ICC), and other parameters reflecting
the intracranial environment. In the conclusion, a comprehensive picture of the intracranial fluid dynamics
influenced by postural changes is attempted, elaborating
more on the acute effects of short-term ortho- and antiorthostatic positions.
This review’s many suggestions can serve as an additional guide for creating novel methods that assess andanalyze the relationship between CSF circulation andcerebral and cardiovascular hemodynamics, which canshed more light on human adaptability in space and otherenvironments with different gravitational forces, as wellas provide practical solutions for medical and research
purposes.
Cerebral autoregulation and hemodynamic effectsof short‑ and long‑term postural changes

The total cerebral blood flow (CaBF) through the internal
carotid (ICAs) and vertebral arteries (VAs) in the supine
position is reported to be around 750–870 ml/min on
average [4–6]. This flow is tightly regulated by cerebral
autoregulation (CA), which is a physiological processthat maintains adequate oxygenated blood supply to thebrain in response to changes in cerebral perfusion pressure (CPP), mainly by regulating the resistance level ofthe blood vessels. CA also regulates the amount of bloodpresent in the brain, which is a major compensatory
mechanism that protects the brain from high intracranialpressure (ICP) [7, 8]. Normally, an increase or decreasein CPP leads to vasoconstriction or vasodilation. CA isPage 2 of 13

activated within 2–5 s after changes in CPP, stabilizing itin the range of 50–150 mmHg [8–11].
There are two approaches to evaluate CA: static anddynamic. The static approach assesses steady-statechanges of CaBF relative to arterial blood pressure, while
the dynamic approach represents CaBF response to rapid
shifts in blood pressure and the time it takes to return tobaseline. CA partly depends on the intrinsic mechanisms,
including the direct response of vascular smooth muscle
to blood pressure alterations and innervation from subcortical neurons or local cortical interneurons [12]. CA
also depends on extrinsic perivascular innervation from
sympathetic and parasympathetic parts of the autonomic nervous system [13, 14]. The latter participates in
the phase regulation of vasoconstrictor and cardiomotor neurons located in the ventrolateral section of the
medulla. The parasympathetic nervous system acts independently of the metabolic needs of the brain and almost
always increases cortical blood flow [1]. Parasympathetic
neurons are also thought to be less influenced by autotrophic reflexes characterized by slow axonal transportand humoral transmission of catecholamines and neuropeptides [15]. It is also assumed that the sympathetic andparasympathetic nervous systems play a significant rolein CA during hyper- and hypotensive conditions, rendering adaptive protection [13].
During instances of body position changes fromupright sitting or standing to horizontal supine, following mechanical stretching of vascular walls in the
carotid arteries irritates sinocarotid pressure receptors.
These receptors transmit electric impulses to sympathetic vasoconstrictor and cardiomotor neurons innervating resistive vessels. Consequently, these impulses
inhibit vasoconstrictor and cardiomotor neurons leading
to a decrease in peripheral resistance, heart rate slowing down, and reduced arterial blood pressure, which, inturn, causes a reduction of minute blood volume. Additionally, parasympathetic cardiomotor neurons also get
excited, which diminishes minute blood volume evenmore [16, 17]. In the described sequence, intermediaryelements such as the solitary nucleus, which propagate
the stimulus further, and parallel controlling structuresin the brain stem, cerebellum, hypothalamus, and limbic
system, were omitted.
The effect of baroreflex modulation on CA is not fully
understood. Still, it is known that baroreflex sensitivity
is antagonistic to CA, judging by the described mechanism of their interaction. An inverse correlation between
them and an enhanced sympathetic tone is consistent
with lower baroreflex sensitivity [18]. The conclusion ofmost of these findings might be that CA mechanisms
are more closely connected to the sympathetic nervous
system. Although there is some evidence that myogenic

Sagirov et al. Journal of Physiological Anthropology(2023) 42:5

influence on CA is more prevalent, this prevalence is only
expressed in determining the lower limit of CA [14]. The
sympathetic mechanism is the largest contributor within
the active region of CA. Therefore, it has a significant
involvement in normal adaptive responses of brain bloodflow.
Although the supporting mechanisms of CA are generally reliable, there are instances of postural changes, suchas high orthostatic stress, that can affect CaBF. Head-up
tilts (HUT) of 60° or more reduce CaBF velocity, registered in the middle cerebral artery (MCA) by transcranial
Doppler sonography (TCD), by approximately 15–20%[19–21]. Sato et al. emphasize that there is a difference inblood flow response in ICA and VA to orthostatic stress.
In their study, CaBF was reduced mainly in MCA and
ICA, while VA blood flow was unaffected. The authors
conclude that this might indicate different dynamic CA
responses evoked to maintain CPP in two major brain
vascular areas during orthostatic stress. The same results,
showing heterogeneity in dynamic CA between ICA and
VA, were obtained in the study using lower body negative pressure (LBNP) [22]. LBNP of − 50 mmHg caused
a reduction of 25% in ICA blood flow and no significant
change in the CaBF of VA. In contrast to these results,
another study by Kaur et al., which implemented moderate to severe LBNP tests up to − 70 Torr, did not findany type of heterogeneous response between ICA andVA [23]. Nonetheless, the majority of studies focusedon orthostatic stress are alluding to the hypothesis thatblood flow in the VAs vascular area decreases only during extreme orthostatic stress, most likely occurring inpredisposed conditions of orthostatic intolerance or
hypotension. In addition, studying a heterogeneous CaBF
response in the intra- and extracranial arteries among
young men during mild postural changes (+ 20° HUTand − 20° HDT), Ogoh et al. suggested that negativechanges in ICP compensate shifts in hydrostatic pressure,thereby stabilizing CaBF in internal carotid and vertebral
arteries. Meanwhile, the external carotid artery may provide a shunting function during HUT, since its blood flow
is highly affected by gravity [24].
In cases of antiorthostatic postural changes, research
indicates that CPP and CaBF remain relatively stable
and within the normal range, regardless of the severityof short-term head-down tilt (HDT) [3, 24–27]. Recent
MRI investigations have shown only a 5–6% reduction
in total CaBF in response to short-term HDTs ranging from − 6 to − 15° [5, 6]. This robustness is achieved
through the adaptive functions of CA, particularly
through the regulation of cerebrovascular resistance,
which differs depending on body orientation. Gelinas
et al. used TCD to report a relative increase in vascular
resistance of middle and posterior brain arteries during

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a 10-min − 90° HDT [3]. Kato et al. found no substantial differences in CaBF velocity in the MCA and transfer function gain between supine and HDT, only notingthat the cerebrovascular resistance index was slightly
higher in − 30° HDT compared to − 10° HDT [27].
In a complex MRI study, Zahid et al. applied − 15°
HDT to examine CSF pulsatile flow, demonstrating a small 6% decrease in average blood flow rate
through internal carotid and vertebral arteries among
15 healthy subjects [6]. Another sophisticated TCD
study investigated acute responses from cerebral andsystemic hemodynamics to transitions between HDT
and HUT in ten healthy individuals, using CaBF velocity and blood pressure in the MCA and cerebrovascular resistance index (CVRi) to establish a proportional
increase in these parameters to the degree of HDT[28]. This study used horizontal position as a reference
to 75° HUT and short-term (15 s) HDT of − 10°, − 25°,and − 55°. The immediate transition from any degreeof HDT to HUT caused a 10–20% reduction in calculated BPMCA and CVRi for a short-time period. However, CaBF velocity had the fastest recovery, returning
to baseline within 5 s after the postural change. The
authors claim that these results demonstrate the highefficiency of CA, at least under conditions of 1 G. They
also accentuated the stability of the dynamic aspect of
CA in healthy subjects, despite a short-lived drop in
the parameters below the CA static range, which wasassessed according to the CPP range of 50–170 mmHg.
Therefore, the given studies consistently prove that CA
in healthy individuals is robust against implemented
postural transitions.
It is doubtful that the same outcomes can be expected
when observing brain blood flow during long-term postural changes, such as head-down bed rest (HDBR),
spanning several hours, days, or weeks. HDBR tests areusually conducted to simulate physiological conditions
during space flights, where the hydrostatic pressure gradient of blood and CSF is absent, causing the pure volume pressure and pressure of surrounding tissues tocome into the forefront, distributing between the lower
limbs and the cranium. The following increase in intracellular and interstitial fluid volume and hemodynamic
and autonomic adaptive-compensatory changes in the
body is associated with an increase in ICP. These homeostatic shifts could lead to abnormal alterations in CA
manifesting after spaceflights, resulting in orthostatic
intolerance [2, 29, 30]. It is observed that only some of
the returned astronauts experience this condition, andthe onset of orthostatic intolerance upon returning to theplanet’s surface depends on the time spent in zero gravity
and is predetermined by gender as well as individual susceptibility to orthostatic stress.

Sagirov et al. Journal of Physiological Anthropology(2023) 42:5

Blaber et al. report controversial results of several studies conducted in the past on the usage of TCD during andafter space flights and HDBR of − 6 to − 13°, concludingthat the state of cerebrovascular autoregulatory mechanisms during these conditions remains elusive [31]. Manyof the reviewed studies measured CaBF velocity in the
MCA to identify CA changes in HDBR tests. However,Montero et al. found no alterations in CBF velocity in
MCA during prolonged 180 min HDT, while CBF velocity was diminishing progressively, and CPP remained
stable [25]. Similar suggestions about lack of precisionin TCD measurement of CBF velocity were expressedby Lewis et al. in their article on transient hypotension
during LBNP [32]. The main problem that is most likely
responsible for these controversial measurements lies inthe technique limitations of TCD. TCD can accurately
assess cerebral blood velocity only if the cerebral vessel
diameter does not change. Considering that the diameters of the measured arteries did change in the mentioned studies, the root of inconsistent results is obvious.
It is recommended to aim for incorporation of several
methodologies by combining or using instead of TCD
duplex ultrasound and MRI which can measure bloodvessel diameter and velocity, enabling more accurate
evaluation of CA during postural changes.
A study that used phase contrast MRI to measure arterial and venous brain hemodynamics in nine healthy
male participants during − 6°, − 12°, and − 18° HDT lasting 4.5 h found a significant decrease in arterial inflow
in all HDT angles compared to supine, with a maximum
total CaBF reduction of 23% in 12° HDT. However, during the transition to − 18° HDT, there was a sudden 9%
uptick in arterial inflow, as well as a 26% surge in venous
outflow [4]. The authors explain that one of the causes ofthis reversal could be the accumulation of metabolites
and ­CO2 in the cerebrovascular system that prevail overthe hydrostatic effects that decrease CaBF. Notably, CaBFin ICAs contributed the most to changes in overall arterial inflow. The most recent MRI study also described a
17% drop in ICA CaBF and a 6% increase in ICA resistive
index after more than 24 h of HDT [33]. Interestingly,
exposure to 3% ­CO2 did not have much effect on CaBF.
These results are true only for ICAs and not for VAs,
which further reinforces the suggestion that blood flow in
VAs could be more strictly regulated than in ICAs.
Despite considerable changes in CaBF during longterm HDTs shown by the respective studies, Kermorgant et al. found that dynamic CA was still improved inhealthy subjects after 21 days of − 6° HDBR [34]. Perhaps
implementing steeper HDT angles over long periods
could yield different results.
Overall, studies on the reactions of CA and CaBF topostural changes suggest that normal CA effectively

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regulates blood supply to the brain during orthostaticand anti-orthostatic body positions. Based on data fromthese studies, CA minimizes blood flow alterations in thebrain and maintains stable CPP during anti-orthostatic
tilts. This is particularly true for short exposures to HDT
and somewhat applicable for HDBR. In addition, changes
in CVRi and autoregulatory index during HDT and
HDBR indicate high CA efficiency [28, 34].
This enhanced state of CA seems paradoxical, asbaroreflex modulation in antiorthostatic positions, evenmore than in supine, should work against CA effects thatraise cerebrovascular resistance through sympathetic
neurons. However, a possible explanation is that stimulation from baroreceptors is insufficient to overcome sympathetic tone or CA influence, which could be positively
modulated by small increases in ICP. Arbeile et al. havesuggested that the increase in cerebrovascular resistancemight be connected to an increase in ICP during the firstdays of HDT [35].
Impairment in CA or its predisposed feebleness could
lead to the development of orthostatic intolerance, which
may become apparent after spaceflights or HDT and
HDBR tests. Therefore, CA could be balancing the sympathetic tone of ICAs and its cerebral arterial network
according to the predominant modulation of baroreflex
or ICP during orthostatic and antiorthostatic posturalchanges. CA remains mostly unchanged regardless of any
type of postural changes, except for VAs, which supply
a more metabolically active vertebrobasilar system andare likely in a persistent state of vasodilation due to constant sympathoexcitation. Studies have shown little to nochanges in CaBF in VAs during HDTs [4, 22, 33], and acouple of articles on the peculiarities of CA in posterior
cerebral artery (PCA) [36, 37] support this conclusion.
However, Nakagawa et al. found evidence that vasodilation occurs in the PCA territory mainly due to higher
metabolic state in the visual cortex when the eyes are
open. Apparently, in a condition with closed eyes, CA in
MCA and PCA operates on the same level. It is important to note that CA assessed in PCA might not necessarily represent CA in VAs, even though PCA is a terminal
branch of basilar artery, which is a continuation of both
VAs.
Therefore, we can see that CA strictly maintains thearterial part of brain blood volume within physiologicalboundaries, at least during short-term postural changes.
Long periods of microgravity or HDT can alter CA
responses leading to manifesting orthostatic intolerance
in some individuals. In this condition CA is functioning fairly adequate during supine and HDTs; however,upon transition to orthostatic positions altered CA cannot readjust CaBF to maintain normal CPP revealing
its developed maladaptation. Other intracranial fluid

Sagirov et al. Journal of Physiological Anthropology(2023) 42:5

compartments, such as cerebral venous blood and CSF,
that are not under CA management, exhibit more flexibility in their flow and volume when body position ischanging, as described further in the article.
Cerebral venous outflow in various body tilt positions

The primary pathway for venous outflow from the brain
is through the internal jugular veins (IJVs), which collect blood from the superior sagittal and rectal sinuses
via the transversal and sigmoid sinuses, and from thecavernous sinuses via the inferior petrosal sinuses. In a
resting supine position, the mean cerebral venous bloodflow (CvBF) is approximately 750 ml/min, with 70–90%
of it flowing through the IJVs and the remainder throughthe vertebral veins (VVs) and vertebral venous plexus [4,38–40].
However, when the body is upright, the distribution ofvenous flow changes dramatically. The lumen of the IJVs
partially collapses due to negative pressure that occurs at
this level as the body is verticalized, which raises the IJVs
above the venous hydrostatic indifference point locatedslightly below the heart level. This leads to increased
resistance to flow in the IJVs and the redirection ofblood down the VVs and other vessels of the extrajugular system supported by the adjacent tissues of the neck
[41–44]. As a result, general venous outflow decreases by
2–2.5 times, to a range of 280–480 ml/min in the standing position. The reduction in CvBF in IJVs can varyfrom 90% (around 70 ml/min) [45] to 60% (roughly 240–
370 ml/min) [40, 43], whereas the CvBF in VVs either
surges from 40 ml/min to 210 ml/min or remains mostly
unchanged. Such variations may stem from differences inthe sensitivity of the measuring equipment or methodological approaches in choosing between upright standingor sitting body positions.
The IJVs start to collapse at head-up tilt angles of
10–30°, and performing the Valsalva maneuver in uprightstanding opens the IJVs again, indicating that cerebral
venous outflow is dependent on central venous pressure[43, 46–49]. Therefore, the IJVs serve as a differential
pressure valve when the body transitions from supine to
upright [26, 50, 51]. The collapse of these veins partiallyredirects CvBF through high-resistance VVs, deep cervical veins, and veins of the vertebral venous plexus, which
splits cerebral venous pressure from central venous
pressure. This also prevents a sudden substantial fall in
ICP during the transition to an upright position, as ICP
decreases only mildly due to partial CSF outflow to thespinal compartment and relatively small cerebral venous
pressure. Thus, the collapse of IJVs greatly influences
CSF dynamics in the craniospinal system in an upright
posture.

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Venous outflow in the brain is highly asymmetrical, as
evidenced by computed and MRI venography observations. The transverse sinus has right-sided venous outflow
in about 40% and left-sided in 18% of subjects examined[48]. Multiple studies consistently show venous outflow
dominance in the right IJV [4, 40, 52]. This asymmetryis likely due to differences in the connections between
cerebral venous system vessels that are common among
the population. In a pilot ultrasonic study by Simka et al.,
IJV asymmetry was highlighted, revealing that the resistance to venous outflow was two times lower in the lower
IJV during lateral decubitus body position than in both
IJVs in the supine position [52]. Due to this asymmetricalstructure, volume gains often occurred in the right IJV.
This reduction in resistance optimizes cerebral venous
outflow, reducing jugular reflux, which is a reverse blood
current, and potentially connected to malfunctions in the
glymphatic system and neurodegenerative diseases [53,54].
It is possible that the asymmetrical venous pathways
in the cranium create various venous outflow patterns.
Doepp and Schreiber identified three patterns in theirstudy article [39]. In the first type pattern, two thirds of
CvBF goes through IJVs, the second type is characterizedby jugular venous flow between two thirds and one thirdof CvBF, and the third type is defined by venous flow in
IJVs of less than one third of the overall cerebral venous
drainage. Using duplex color sonography on 50 healthy
participants during supine, the researchers showed thatthe first type pattern was found in 72% of them, the second type was distributed among 22%, and the third type
was present in only 6%. This data indicates that IJVs are
the primary pathway for cerebral venous outflow in mosthorizontal body positions. However, the authors notedthat CvBF in VVs did not differ significantly between thejugular first and non-jugular third drainage types. Thesefindings suggest that extrajugular drainage pathways,
such as deep neck veins, are more involved than expected
and play a significant role in the dynamics of venous outflow during orthostatic positions.
It appears that the behavior of venous outflow in antiorthostatic positions is opposite to that in orthostasis.
According to Arbeille et al. [35], jugular vein enlargement was significantly observed during prolonged − 6°
HDT (which is essentially HDBR) and spaceflights.
They reported that after 4–5 days of HDT, the crosssectional area (CSA) in IJVs increased by 8%, after aweek it grew by 49%, and even on the 42nd day of HDT,
a 40% jugular vein enlargement was still observed.
Similar results were reported in spaceflight, with IJVCSA increasing by 33–47% after 1 week to 6 months.
However, such a significant increase in blood filling
may lead to blood stagnation and brain edema. When

Sagirov et al. Journal of Physiological Anthropology(2023) 42:5

the body is tilted to the Trendelenburg position (− 25°
HDT), the IJVs’ lumen can increase by an average of
19% compared to the supine position [55]. MarshallGoebel et al. [4] reported that the total jugular venous
cross-sectional area gradually expanded from 0.6 ± 0.2­cm2 in the supine position to 1.3 ± 0.5 ­cm2 at –18°
HDT. However, CvBF velocity in IJVs was found to be
decreased by almost half at –12° and –18° HDT compared to the horizontal position. Recent MRI studies [5,6] reported a 15–30% increase in IJV CSA, little gains
in average jugular venous outflow, and a significant
drop in IJV CvBF velocity during short-term HDT of–12 to –15°. These findings suggest blood stagnation,
which can lead to an increase in cerebral venous pressure and, according to Davson’s equation, an inevitablerise in ICP [50, 56].
Based on the available studies, it can be concluded
that posture has a significant impact on cerebral venous
outflow. When the body is in a horizontal position, themajority of venous blood flows out of the brain throughthe IJVs, with a higher venous flow rate observed in theright-sided vessels due to the anatomy of the intracranial venous network. However, in lateral decubitus
positions, most of the cerebral venous blood volume
flows through the IJV on the side of the body on which
the person is lying. The transition from supine to
upright posture results in IJV collapse, which depends
on the degree of orthostasis. In an upright posture,
venous outflow becomes more prevalent in veins outside of the jugular system, such as the VVs, deep cervical veins, and vertebral venous plexus. This collapseof the IJV and the switch to highly resistive veins are
believed to play a protective role in counteracting
sharp falls in ICP by disconnecting cerebral and central
venous pressure during upright posture.
Antiorthostatic HDTs can lead to even greater expansion of the IJVs, but not necessarily to a higher venous
outflow rate, due to the influence of central venous
pressure on CvBF and ICP. This phenomenon is particularly relevant to spaceflight, where weightlessness
does not prevent the continuous transmission of central venous pressure to the brain, leading to increased
ICP and related symptoms. Therefore, dynamic shifts
in CvBF and central venous pressure during posturalchanges can cause interruptions or reinforcements in
the hydrostatic pressure gradient, ultimately affecting
intracranial pressure. In the following sections, we will
discuss how CaBF and CvBF are interrelated with ICP.
Cerebrospinal fluid dynamics, intracranial pressure,and intracranial compliance during postural changes

Originating more than two centuries ago, the MonroKelly hypothesis establishes clear fundamentals about the

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relationships between brain matter, cerebral blood volume, and CSF [57]. Alexander Monro and George Kellyin the eithteenth century established the basis of thishypothesis, which explains the behavior of liquids inside
a closed space, specifically inside the cranium. Their successors later modified the hypothesis. It claims that the
total volume of brain matter, CSF, and blood inside a hermetically enclosed skull is constant. None of the components can be compressed, and an increase in one of themis only possible if the other one or two are displaced outside. It is worth adding that the hypothesis has undergone
a number of corrections and additions to become what
it is today. In the beginning, the founders were unawareof the third fluid, liquor, or CSF. Thus, only two components were taken into account. In the next century, CSF
became part of the equation of intracranial hydrodynamics through the efforts of French physiologist Magendie
and English physician Burrow. Today, the Monro-Kelly
hypothesis provides theoretical explanations for a varietyof pathological conditions associated with high ICP, liquor leakage, brain tumors, etc.
Currently, the cranial cavity is considered a closed
space with rigid walls filled normally by 85 − 87% withbrain matter, 9 − 10% with CSF, and 4 − 5% with theblood [58, 59]. Overall, intracranial CSF pressure reflects
ICP and is defined by the dynamic balance between CSF
secretion, absorption, and flow resistance. Normal values of CSF pressure, measured in the supine position,vary between 7 and 15 mmHg in adults. CSF pressure
and ICP are dependent on many factors such as systolicpulse wave, respiratory cycles, intraabdominal pressure,arousal, physical activity, central venous pressure, andbody position [60, 61].
Both active body movements and passive posturalchanges entail a shift in the direction of gravitational
force that affects the craniospinal system, which includes
the brain, spinal cord, CSF, cranial and spinal subarachnoid space, and the vasculature filled with blood. This
shift results in brain and spinal cord oscillations, CSF
redistribution in their subarachnoid spaces, the adaptive
response from cerebroarterial circulation, and alterations
in cerebral venous pressure that ultimately cause changes
in ICP.
An important and commonly used parameter of intracranial dynamics is cerebral or intracranial compliance(ICC). Regarding the whole craniospinal system, it could
also be appropriated as craniospinal compliance. ICC represents the slope of the volume-pressure curve (∆V/∆P),
where changes in the intracranial volume bring reciprocalchanges in ICP (Fig. 1).
The volume-pressure curve starts with the maximum values of ICC, which represents the period of
spatial compensation. As more volume is infused

Sagirov et al. Journal of Physiological Anthropology(2023) 42:5

into the subarachnoid spaces, the curve graduallyrises until there is no more reserved space left, whichmarks the end of the period of spatial compensation.
At this point, the curve sharply transitions to the spatial decompensation phase, and the ICC value rapidly
becomes low [62]. The significance of ICC lies in its
ability to assess the redistribution of volume in intracranial compartments, particularly in liquid compartments such as CSF, arterial, and venous blood. The
pressure redistribution in these compartments follows
the volume reallocation and determines the ICP atlarge. Moreover, ICC is primarily used as an index todemonstrate the brain’s capability to minimize changes
in ICP by adjusting the volumes of intracranial compartments, mainly CSF and cerebral blood. ICC istherefore characterized as a measure of intracranial
physiological reserve (Fig. 2). Average normal supine
ICC values range from 1 to 1.3 ml/mmHg. ICC levels
lower than 0.5 ml/mmHg are considered critical andindicate a sharp decline in intracranial reserve capabilities, regardless of baseline ICP [58, 59, 61].
It should be noted that intracranial and spinal cavities
contribute unequally to the total compliance of the craniospinal system. In a study on cats, the intracranial part
accounted for 68% of the total compliance in CSF spaces,
while the spinal part accounted for 32% [63]. A similar proportion was found in research conducted among
human subjects, with up to 50% of compensatory capabilities falling on supratentorial space, 30% on subtentorial space, and 20% in the spinal canal [58].
The first observations of changes in ICP when posture is altered were made by puncturing subarachnoid
spaces to measure CSF pressure at different sites of the

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Fig. 2 Proportional changes in volumes of intracranial compartments
and ICC in spatial compensation and decompensation phases. Under
normal physiological and compensatory conditions, ICC is high,indicating that there is spare space in the cranium and ICP remains
relatively stable. However, in the decompensation phase, due toabnormal increases in overall intracranial volume, ICC becomes
critically low, resulting in high ICP values. In this phase, any additional
volume added will cause ICP to increase exponentiallycraniospinal axis. In 1935, Loman et al. [64] demonstrated with lumbar and occipital punctures on psychiatric patients that hydrostatic pressure decreased in the
suboccipital cistern and increased in the lumbar subarachnoid space simultaneously during the transition froma supine to standing position. Similar work was done byMagnæs [65], who chose the upper point of measurement
to be on the level of the lateral ventricles. On 72 control
patients without intracranial pathology, he produced

Fig. 1 Two graph variants of the volume-pressure curve that depict ICC. A The classical volume-pressure curve formed by the ratio of changes inintracranial volume (∆V) to changes in ICP (∆ICP). B The graph with absolute ICP values on the ordinate axis instead of differential ICP values. In thisgraph, the volume-pressure curve and its possible continuation in a dashed line are roughly shaped according to the first graph and the sources[58, 59, 61, 62]

Sagirov et al. Journal of Physiological Anthropology(2023) 42:5

the same results and found that, in most cases, the zero
CSF pressure point was located between the levels of theoccipital protuberance and the seventh cervical vertebra.
He also discovered that the hydrostatic indifferent point
in CSF space, where pressure remains the same regardless of body position, stretched from C-6 to T-5 among
patients in the control group.
Williams, by applying concurrent ICP measurementsfrom ventricles and lumbar subarachnoid space inpatients with various neurological conditions, establishedthat CSF pressure is equal to atmospheric pressure in theforamen magnum [66]. Studies in neurology and neurosurgery comparing ICP values between groups of hydrocephalic patients with pressure shunts or without themand patients with normal ICP showed that the absenceof a shunt predisposed to stable positive ICP measured
inside ventricles regardless of postural changes. Meanwhile, shunting leads to a significant drop in ICP up to
negative values in an upright position. For instance, toprove the existence of negative ICP, Fox et al. recorded
ICP measurements of + 20 to + 180 ­mmH2O (+ 14.7
to + 132.4 mmHg) in the horizontal position and -140
to + 70 ­mmH2O (− 102.98 to + 51.5 mmHg) in an orthostatic position [67]. Chapman et al. reported that when
patients with various shunt systems transitioned toorthostatic positions of 30 to ­90°, their ICP inside ventricles fell to a negative range of − 15 to − 30 cm ­H2O(− 11.03 to − 22.07 mmHg) [68]. The use of an antisiphon
device mitigated such a dramatic decrease in ICP, whichstarted to vary between − 7 and + 3 cm ­H2O (− 5.15
to + 2.21 mmHg). Patients without hydrocephalus andshunts exhibited a lowering of intraventricular pressureto − 5 to + 5 cm ­H2O (− 3.68 to + 3.68 mmHg) immediately after HUT. Contemporary sources confirm that themean negative normal ICP in an upright standing position is − 5 mmHg [26, 61, 69]. However, excluding factors
such as IJV collapsibility during orthostatic position or
the use of shunting systems in hydrocephalus cases, ICP
could even dip to − 15 mmHg [51].
The rate of reduction in ICP depends on the degreeof orthostatic tilt. Small angles ranging between 0° and
30–45° result in quick decreases in ICP proportional to
the tilt, whereas high-degree angles above 45° reduce ICP
slowly [50, 70, 71]. The jugular collapse, which becomes
more pronounced above 30° angles, and increased
intraabdominal pressure and excessive CSF filling of
the spinal buffer are believed to be responsible for thisdisparity. This explanation could also provide insight
into the differences in ICP between upright sitting andstanding.
A decrease in ICP during orthostatic posture is likely
to bring an increase in ICC. Several studies have investigated intracranial physiology under the impact ofPage 8 of 13

postural changes, and specific attention has been drawn
to this prediction. Alperin et al. discovered that after transitioning from supine to upright sitting, ICC increased bya factor of 2.8 with a corresponding decrease in ICP [72].
The authors explained that these changes in parametersindicate that ICP is relatively low in the upright position
because lesser blood and CSF volumes remain in respective compartments after they shifted into lower parts ofthe body.
Gehlen et al. introduced a generic lumped-parameterbiomechanical model of the CSF and cardiovascular system [51] that used arterial blood inflow to explain thehydrodynamic physiology in supine and upright positions. The model assumed a lower spinal compliance
contribution (35%) in a supine position, which further
reduced in an upright posture (10%). This suggests thatsome portion of intracranial content is unloaded into thespinal compartment when acquiring an upright posture,
leading to an increase in ICC while spinal compliancediminishes.
However, some studies have reported conflicting
results. For example, a study on 13 neurological patientsby Raube et al., which applied invasive intraventricularsensors, found no substantial differences in ICC during
various head-up tilt tests [73]. Similarly, a more recent
cross-sectional study using ICP monitoring and pulse
amplitude measurements in 101 patients with suspected
CSF dynamics disorders discovered that pulse amplitude
was higher in sitting and standing positions comparedto supine, indicating that an upright posture is associated with a minor reduction in ICC [74]. These controversial findings could be due to the fact that some studies
suggesting an increase in ICC during upright are noninvasive and conducted on healthy individuals or makepredictions based on a model, while other research articles report a small drop or no changes in ICC duringorthostasis and use invasive measurement methods onpatients with various neurological impairments.
In cases where the body is positioned antiorthostatically,a higher ICP is expected compared to supine or orthostatic positions. Studies have shown that during short-termand long-term HDT of − 6°, pressure transducers initially
recorded a slightly higher ICP (Δ1.8 ± 0.5 mmHg) compared to supine, which then lowered after a few hours tomatch baseline supine values [75]. Non-invasive assessments of ICP alterations in − 10° HDT, through the useof arterial blood pressure and cerebral blood flow velocity, have shown that ICP could range roughly between 8
and 30 mmHg [76]. Petersen et al. demonstrated a risein ICP in neurosurgical patients without a pathological
ICP profile from 9.4 ± 3.8 mmHg in horizontal supine
to 14.3 ± 4.7 mmHg in − 10° HDT and 19 ± 4.7 mmHg
in − 20° HDT [26]. Another non-invasive ICP (nICP)

Sagirov et al. Journal of Physiological Anthropology(2023) 42:5

analysis of data from 17 healthy subjects estimated 12%
and 37% increases in nICP, from 7.8 ± 2.8 mmHg during
a horizontal position to 8.9 ± 2.6 mmHg in − 10° HDT and
12.4 ± 3.4 mmHg in − 30° HDT [27]. Overall, antiorthostatic tilts do raise ICP, but only within normal physiological confines when considering the results of the describedstudies that used small angles or acute exposure to more
severe tilts.
Kato et al. suggested that to prevent ICP from exceeding an upper normal limit during HDTs, CA must not
be impaired [77]. This suggestion is primarily based on asystematic review that revealed a moderate to strong correlation between high ICP (≥ 20 mmHg) and impaired
CA. The possibility of malfunctioning CA being the maincause of intracranial hypertension is still up for debate.
Nonetheless, the severity and duration of antiorthostatic
positions could certainly be contributing factors to CA
destabilization and pathological increase in ICP. Case
reports of robotic laparoscopic surgeries provide examples of pronounced HDTs of 30–45° that lead to abnormally high ICP values, up to the development of brain
edema and various neurological complications [78, 79].
As mentioned earlier, changes in ICP are connected tocorresponding changes in central venous pressure, especially during antiorthostatic tilts. Several studies haveemphasized the predominant dependence of ICP during supine and HDT on central venous pressure, which
impacts ICP through the venous sinuses and internal jugular veins [4 − 6, 26, 27, 44, 50, 75]. Therefore,
ICP increase reflects to a large extent the rise in central
venous pressure when the body is tilted downwards.
When discussing ICC, it is logical to consider its
decrease during antiorthostasis as it decreases during
the transition from upright to supine. If the hydrostaticpressure gradient of the venous blood and CSF column
is directed towards the head, additional volume inside
the cranium emerges. When compensatory reserves arefilled up along with hindered CSF and venous outflow,
it causes an unavoidable rise in ICP, as demonstrated bystudies that used various HDTs. However, according toLawley et al., which used ICP pulse amplitude as an indicator of ICC, it was unaltered or even slightly improvedin prolonged − 6° HDT [75]. Shedding some light on thismatter are MRI studies that measure CSF flow pulsations during cardiac cycles. We already discussed someof them, mainly in the section about CA. The main principle of this technique is based on the characteristics of
ICP waves, which are largely modified by pulsations of
intracranial arteries, and thus, ICP distribution can be
estimated over the phases of the cardiac cycle [80–82].
Alperin et al. proposed the parameter of intracranial
volume change (ICVC), which is characterized as the difference between the inflow and outflow of fluids into andPage 9 of 13

out of the skull during the cardiac cycle. This parameter
was then used to assess changes in ICP and ICC among
healthy individuals, patients with intracranial hypertension, and baboons [83]. The researchers estimated anaverage range of ICVC in supine healthy volunteers withnormal ICP to be 0.34–1.3 ml, which constituted 0.1% of
the overall intracranial volume. In their follow-up study,
Alperin et al. discovered that after transitioning from asupine to an upright sitting position, ICVC increased
nearly twofold, corresponding to an increase in ICC [72].
Ishida et al. used a similar technique and found no significant difference in ICVC between supine and HDTof − 6° and − 12°, only a small surge in peak-to-peak pressure gradient [5]. The SPACECOT study suggested aqueductal CSF velocity amplitude for the measurement of
CSF pulsatility and representation of changes in craniospinal compliance [33]. Six male participants in the study
showed a 13% increase in CSF velocity amplitude in prolonged − 12° HDT compared to supine, though not statistically significant. However, brief exposure to 3% ­CO2
during HDT raised CSF velocity amplitude by 21%, which
was statistically significant. Although this study did notdemonstrate the definitive effect of HDT on craniospinal
compliance, these results imply that if CA were to lose
control and allow excessive arterial vasodilation in thebrain, it would increase ICP and reduce compliance.
Mild HDTs may not be radical enough to lower ICC
substantially, but even − 30° HDT only raises ICP within
the physiological range unless the cerebrovascular system is altered or impaired. ICP changes between about
10 mmHg and 20 mmHg may normally only trigger
minuscule perturbations in ICC, considering that ICC
alters exponentially in accordance with the volumepressure curve (Fig. 1). In the end, this assumption seems
reasonable.

Conclusion
To summarize the review, we will briefly discuss the main
topics covered. The craniospinal system’s most tightly
regulated part is CaBF, which CA keeps within physiological boundaries to ensure adequate CPP and normal brain
function, even during postural changes. Several studies
have demonstrated CA’s effectiveness during tilt-tests,
zero gravity environments, and LBNP. However, impaired
CA or high baroreflex sensitivity can cause noticeable
shifts in CaBF, especially during high orthostatic stress.
CA insufficiency has also been suggested as one of thecauses of high ICP during HDTs and spaceflights. ICA
and VA show heterogeneity in CaBF, with ICA mostly
accounting for CaBF alterations during postural transitions due to the direct effects of baroreflex that impacts
CA mitigating sympathetic tone. Unlike ICA, VA has
seemingly unaffected vascular sympathetic tone and does

Sagirov et al. Journal of Physiological Anthropology(2023) 42:5

not exhibit any large CaBF fluctuations during posturalchanges, LBNP, and probably microgravity.
The cerebral venous system generally reacts passively
to postural changes due to bidirectional flow provided by
the fixated vascular walls of venous sinuses and venous
plexus of the neck. However, collapse of IJVs in orthostatic positions causes a substantial fall in CvBF thatbegins to flow predominantly in the extrajugular venous
network. In antiorthostatic positions, CvBF increases
compared to supine and orthostasis, but the rate ofvenous outflow remains the same or slows down depending on the degree of HDT. These changes lead to a higher
cerebral venous pressure and subsequent rise in ICP.
ICP is a cornerstone of intracranial relationships
between the brain, cerebral blood, and CSF. The MonroKelly hypothesis explains these interrelations, claimingthat the total volume of brain matter, CSF, and bloodinside the enclosed cranium is constant, and an increasein one of them is only possible if the other or two are displaced elsewhere. Examining ICP changes in different
body positions, the ICP dependency on flow dynamics
of arterial and venous blood and CSF should be considered. CvBF is directly related to cerebral venous pressure,which is the main contributor to ICP. CA, as previously
stated, preserves CaBF within a certain range, modulating ICP, particularly during HDT and microgravity when
it is crucial to control blood filling in the cerebral arteries and prevent elevated ICP. CSF, similarly to the venous
blood in the brain, is a passive participant in the craniospinal system during postural changes. CSF influences
ICP, ICC, and other intracranial physiology parameters,
but to a lesser extent than CvBF. In the orthostatic body
position, CSF volume mainly resides in spaces of the
spinal compartment due to the direction of the gravitational vector. This results in relatively high CSF pressure
in lumbar subarachnoid spaces, zero liquor pressure on
the level of cervical vertebrae, and negative ICP. In supine
and antiorthostatic tilts, the opposite occurs, with CSF
and venous blood flowing more into the skull, leading tohigher ICP and a reduction in ICC.
Based on the findings and conclusions of the discussed
articles and assuming normal neurological conditions,with no significant alterations in brain mass or intracranial volume, the ratios of CaBF, CvBF, and CSF flow
during postural changes can provide insight into the distribution of intracranial fluid compartments (arterial andvenous blood, CSF) in orthostatic, supine, and antiorthostatic body positions (Fig. 3).
Supine position is considered a reference point sincenormal values of ICP, ICC, CaBF, and other parameters
are largely obtained in this body position, where arterial blood inflow and venous outflow should be roughly
equal.

Page 10 of 13

When a human body shifts from a supine to an uprightstanding position, there can be a progressive drop in
CvBF, cerebral venous volume, and pressure due tothe collapse of IJVs and passive flow of venous blood
through the remaining open resistive vessels of VVs andvertebral venous plexus. Meanwhile, CaBF, dependingon baroreflex sensitivity and calibration by CA, will staywithin the same range as before or may reduce mainly
due to decreased blood flow in ICAs. Therefore, in normal conditions, arterial blood volume will likely remainunchanged, but the predisposition to orthostatic stress
may decrease it to some degree.
Intracranial CSF volume is expected to decrease asa portion of it would move into the spinal canal andspinal subarachnoid spaces. This is supported by thefindings of the mentioned MRI studies on CSF flow
pulsatility that demonstrated diminished oscillatory
CSF volume in upright positions [72] and greater CSF
volume displacement in supine positions [84]. Negative ICP values and increased ICC in the upright position also prove that some limited loss of intracranial
fluid volume does occur. Additionally, due to the aforementioned events, CSF oscillation waves tend to havesmaller amplitude and are less synchronized with anarterial pulse.
During antiorthostasis, changes in intracranial
dynamics are opposite to those described in orthostatic positions, with some caveats. ICP is typicallyhigher in HDTs than in supine and HUT, but it usually remains under 20 mmHg in an unimpaired craniospinal system. The ICP increment is largely connectedto the rise of cerebral and central venous pressure
because of the retrograde partial inflow of venous
blood during antiorthostatic tilting. IJV CSA substantial expansion, slowdown of CvBF velocity, and no
significant changes in cerebral venous outflow suggest venous flow stagnation in the cerebral veins. CSF
exhibits similar behavior as cerebral venous blood andmoves in a caudocranial direction during HDT, contributing to the general increase in ICP, though to alesser extent. Meanwhile, CaBF is mostly stable andchanges in a small range under short periods of HDTsof various degrees. CA maintains this CaBF stability
through the increase of cerebrovascular resistance andby restricting the cerebral pool of arterial blood. Furthermore, the role of arterial pulsations as the driverof venous and CSF pulse waves should be even more
pronounced due to an intracranial environment withhigher pressure. These mechanisms play an important part in preventing pathologically high ICP and
the development of neurological conditions, such as
brain edema, when the body is tilted backward or during microgravity. However, there is no clear consensus

Sagirov et al. Journal of Physiological Anthropology(2023) 42:5

Page 11 of 13

Fig. 3 Concept diagram of potential volume interrelationships of intracranial compartments and compliance. Since brain volume does not
significantly change under normal physiological conditions, it is considered constant and is not included in the diagram. The up and down arrows
over the compartments indicate an increase or decrease in the respective fluid flow. The dashed arrows and lines represent hypothetical changes
due to limited evidence or controversial data. On the right side, the literature studies supporting the depicted volume distribution and ICC changes
are presented. The ICP values in the antiorthostatic position are assumed to increase to an upper normal limit of 20 mmHg in healthy individuals

among researchers on the effects of long-term HDTs,
and the possibility that longer duration and steeper
slope of HDT could negatively impact CA and lead to
intracranial hypertension should be kept in mind. The
data on antiorthostatic changes in ICC is inconsistent and suggests either that compliance is unaffectedor that there are small, insignificant reductions incompliance.
In summary, by examining the effects of different
body positions on CaBF, CvBF, CSF, and ICP, we cangain a comprehensive understanding of how posture
impacts cerebral hemodynamics and ICP. However,
it is important to note that there may be other factorsthat contribute to intracranial dynamics in different
body positions that were not considered in this discussion. For example, the effect of central venous pressure
on ICP during HDTs may be mild in rare cases of IJVvalves, resulting in smaller increases in ICP. Additionally, the impact of postural changes on the rate of CSF
production and absorption has not been explored.
Further complex evaluation of intracranial physiology
through various means under the influence of shortor long-term postural changes can result in a moredetailed description of its processes and a better prediction of its changes.

Abbreviations
HDT	Head-down tilt
HUT	Head-up tilt
HDBR	Head-down bed rest
LBNP	Lower body negative pressure
MRI	Magnetic resonance imaging
TCD	Transcranial Doppler sonography
CSF	Cerebrospinal fluid
ICP	Intracranial pressurenICP	Non-invasively estimated intracranial pressure value
ICC	Intracranial compliance
ICVC	Intracranial volume change
CaBF	Cerebral arterial blood flow
CvBF	Cerebral venous blood flow
ICA	Internal carotid artery
VA	Vertebral artery
MCA	Middle cerebral artery
IJV	Internal jugular vein
VV	Vertebral vein
CA	Cerebral autoregulation
CPP	Cerebral perfusion pressure
BPMCA	Blood pressure in middle cerebral artery
CVRi	Cerebrovascular resistance index
CSA	Cross-sectional area
Acknowledgements
Not applicable.
Authors’ contributions
All authors contributed to the writing, illustration, and reviewing of the manuscript. AVS and EAA were the main writers of the section “Cerebral autoregulation and the hemodynamic effects of short- and long-term postural changes.”
AYY and NLG contributed largely to the section “Cerebral venous outflow
in various body tilt positions.” TVS and AS composed the section “Cerebrospinal fluid dynamics, intracranial pressure, and compliance during postural

Sagirov et al. Journal of Physiological Anthropology(2023) 42:5

changes.” AS was also responsible for the congruency of the sections and forwriting the conclusive part of this review. The authors read and approved thefinal manuscript.
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Availability of data and materials
Not applicable.

Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Received: 20 January 2023 Accepted: 1 April 2023

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