During which phase of the cardiac cycle is freshly formed cerebrospinal fluid released into the brain ventricles: systole or diastole?

Commentary (pdf)

Preprint updated version Feb  2026: DOI:https://doi.org/10.13140/RG.2.2.34101.54242/1

This commentary was originally published in 2013 (PDF linked in the title) and updated in Feb 2026 (DOI below). The update does not introduce substantive conceptual changes.

The latest version on CERN Zenodo, March 2026, for citation: Cardiac Cycle–Dependent Release of Freshly Actively Formed Cerebrospinal Fluid: Insights From Physiological and Mathematical Analysis https://doi.org/10.5281/zenodo.18783880

Darko D. Lavrenčič

Abstract

Freshly actively formed (FAF) cerebrospinal fluid (CSF) is released into the brain ventricles (BV) during the diastolic phase of the cardiac cycle when net caudal CSF flow or net CSF volume accumulation exists. In systole, the choroid plexuses swell together with the brain and push the CSF caudally. In diastole, both contract together, and the choroid plexuses refill the ventricles with fresh CSF (push-and-refill mechanism).

Introduction

There are numerous studies and experiments describing CSF behavior during the cardiac cycle, but we still do not know when exactly the new FAF CSF is released into the BV.

Discussion

During the cardiac cycle in its systolic phase, the volumes of the BV decrease by compression of the brain and expansion of the plexus choroideus (PC) (Zhu, Xenos et al. 2006). In diastole, the volumes of the BV are restored.

During systole, the CSF is expelled caudally due to additional pressure on the BV and returns rostrally during diastole due to negative pressure in the BV – the process known as to-and-fro movement of CSF. Because the caudal CSF flow is greater than rostral, there is net caudal CSF flow (Nilsson, Stahlberg et al. 1992). Theoretically, FAF CSF could be released into the BV either during systole or during diastole. If it were released during systole, the PC cells would have to produce extra pressure for FAF CSF transport into the BV, which would require extra energy. If, on the other hand, FAF CSF was released during diastole, this, as a passive process (suction), would require no extra energy.

An experiment on cats was published (Oreskovic, Klarica et al. 2002) in which we may find an answer to this question. Authors describe an experiment with a plastic cannula introduced into the aqueduct of Sylvius during which they observed no CSF circulation at physiological CSF pressure. They also observed no FAF CSF release into BV. If FAF CSF were released into the BV during systole, they would have inevitably observed net caudal CSF flow. During diastole, there was no negative pressure because the open plastic cannula, according to Pascal’s law, had not provided negative pressure in BV, which could have enabled the passive process of FAF CSF release (suction) from PC cells. Consequently, there was no caudal CSF flow either, as they observed CSF pulsations of positive pressure at the open end of the plastic cannula. It can be concluded, therefore, that when net caudal CSF flow exists, the FAF CSF is released into the BV during diastole.

Conclusions

FAF CSF is released into the BV during the diastole of the cardiac cycle when net caudal CSF flow or net CSF volume accumulation exists.

Competing interests: The author declares that no conflict of interest exists.

References

Nilsson, C., et al. (1992). “Circadian variation in human cerebrospinal fluid production measured by magnetic resonance imaging.” Am J Physiol 262(1 Pt 2): R20-24.
Abstract. Recent advances in magnetic resonance imaging have made it possible to visualize and quantify flow of cerebrospinal fluid (CSF) in the brain. The net flow of CSF through the cerebral aqueduct was used to measure CSF production in six normal volunteers at different times during a 24-h period. CSF production varied greatly both intra- and interindividually. The average CSF production in each time interval showed a clear tendency to circadian variation, with a minimum production 30% of maximum values (12 +/- 7 ml/h) approximately 1800 h and a nightly peak production approximately 0200 h of 42 +/- 2 ml/h. The total CSF production during the whole 24-h period, calculated as an average of all measurements, was 650 ml for the whole group and 630 ml for repeated measurements in each time interval in one of the volunteers.

Oreskovic, D., et al. (2002). “The formation and circulation of cerebrospinal fluid inside the cat brain ventricles: a fact or an illusion?” Neurosci Lett 327(2): 103-106.
Abstract. Formation and circulation of cerebrospinal fluid (CSF) have been studied in the isolated brain ventricles of anesthetized cats by a new approach and under direct observation. A plastic cannula was introduced into the aqueduct of Sylvius through the vermis cerebelli and the outflow of CSF from the cannula was used as the CSF formation and circulation index. During the 60 min of observation at a physiological CSF pressure not a single drop of CSF escaped out of the end of the cannula. This indicates that CSF net formation and circulation inside the brain ventricles, proposed by classical hypothesis regarding CSF dynamics, should be at least re-evaluated.

Zhu, D. C., et al. (2006). “Dynamics of lateral ventricle and cerebrospinal fluid in normal and hydrocephalic brains.” J Magn Reson Imaging 24(4): 756-770.
Abstract. PURPOSE: To develop quantitative MRI techniques to measure, model, and visualize cerebrospinal fluid (CSF) hydrodynamics in normal subjects and hydrocephalic patients. MATERIALS AND METHODS: Velocity information was obtained using time-resolved (CINE) phase-contrast imaging of different brain regions. A technique was developed to measure the change of lateral ventricle (LV) size. The temporal relationships between the LV size change, CSF movement, and blood flow could then be established. The data were incorporated into a first-principle CSF hydrodynamic model. The model was then used to generate specific predictions about CSF pressure relationships. To better-visualize the CSF flow, a color-coding technique based on linear transformations was developed that represents the magnitude and direction of the velocity in a single cinematic view. RESULTS: The LV volume change of the eight normal subjects was 0.901+/-0.406%. Counterintuitively, the LV decreases as the choroid plexus expands, so that they act together to produce the CSF oscillatory flow. The amount of oscillatory flow volume is 21.7+/-10.6% of the volume change of the LV from its maximum to its minimum. CONCLUSION: The quantification and visualization techniques, together with the mathematical model, provide a unique approach to understanding CSF flow dynamics.