Flip-flop switch et bâillements
Prostaglandines, adénosine, sommeil & bâillements
Leptine, ghréline, histamine et bâillements







haut de page

mise à jour du
31 décembre 2002
Neuroscience letters
2002; 327; 103-106
 The formation and circulation of cerebrospinal fluid inside the cat brain ventricles:
a fact or an illusion ?
D Oreskovic, M Klarica, M Vukic
Medical Faculty University of Zagreb Croatie


It has been generally accepted that cerebrospinal fluid (CSF), bathing the central nervous system, is mainly produced within the cerebral ventricular system, and circulates as a slow river from the brain ventricles towards the cortex subarachnoid space to be absorbed across the arachnoid villi into the venous sinuses.
From time to time, this hypothesis bas been challenged on the basis of some experimental data. However, in spite of the incompatibility of differences between the mentioned hypothesis and these experimental results, the hypothesis still persists in the unchanged form. Namely, the methods applied to determine the way of CSF formation and circulation have been those that provide indirect inspection of the aforementioned processes by following changes in the characteristics or behavior of a substance after its application into the CSF system. For example, dilution of substances applied in CSF has most frequently been used as a measure of the CSF formation while the distribution of (labelled) substances all over the CSF system has most frequently been used as a marker of the CSF circulation. So, any mistake in the interpretation of the dilution (escape of substances into the brain tissue, the mixing problem, etc.) or distribution (molecular weight; the site and way of application, etc.) of substances in CSF will result in questionable and often contradictory conclusions regarding the CSF formation and circulation.
To avoid the indirect study of the CSF formation and circulation we developed a new experimental model in which these two physiological parameters were examined under direct vision. The first attempt of a direct vision study was shown in our preliminary study. That attempt consisted of a surgical approach with poor control of the CSF and atmospheric pressure. For this reason, in new model, presented in this paper, the aqueduct of Sylvius of anaesthetized cat was cannulated by a plastic cannula and surgical reconstruction was done so that the CSF system was completely protected against any uncontrolled influences of atmospheric pressure and CSF leakage from subarachnoid and ventricular spaces. Thus. the relationship between the ventricular and subarachnoid CSF pressures was established in a physiological range without a transmantle pressure gradient which is a crucial advantage of our model. Namely, in case of pathway obstruction, the absence of a transmantle gradient would not cause a possible CSF flow from the ventricles through the brain tissue into subarachnoid space, which was suggested by Milchorat. In addition to that, the CSF pressure control is also important because it has been shown that the CSF formation is a pressure dependent process.
If CSF is mainly formed inside the brain ventricles and absorbed in the subarachnoid space, it has to circulate at a physiological CSF pressure through the aqueduct of Sylvius or, as in our model, through the plastic cannula positioned in the aqueduct. Therefore, the direct (visual) observation of the CSF outflow throughout the external end of the cannula, adjusted to the physiological CSF pressure, should represent the direction of the CSF circulation from the ventricles to the subarachnoid space. The collected volume of CSF divided by the time of collection should represent the rate of the CSF formation. According to our previous results, where the CSF formation in cat's brain ventricles was measured indirectly by the dilution of blue dextran in CSF and the rate of formation was calculated by the equation of Heisey et al, the rate of formation at least 4.5µl/ min should be expected.
[...] These findings clearly indicate that, in case of the experimentally produced CSF formation, the CSF circulation was established and CSF moved freely through the ventricular system, from the site of infusion (lateral ventricle) via the aqueduct of Sylvius to the external end of the plastic cannula, with the velocity of the circulation being equal to the rate of infusion. Also, neither the absorption nor the net formation of CSF were observed inside the brain ventricles, because neither the reduction or the enhancement outflow were detected.The obtained results apparently indicate that no CSF formation exists inside the brain ventricles, and consequently that CSF does not circulate through the brain ventricles at all.
The presented data largely correspond to the new hypothesis suggested by Bulat which starts from the assumption that hydrostatic and osmotic forces operate between the CSF volumes in the way similar to the way they regulate the volume of extra-cellular fluid in other organs. Hydrostatic and osmotic forces seem to play the main role in the regulation of the CSF volume according to this new hypothesis, and it seems that the imbalance between these forces will result in changes in the CSF volume.
[...] In conclusion, in spite of the fact that in our model animals were under anaesthesia and that the fourth ventricle was excluded from the investigation, the classical hypothesis of the CSF formation and circulation cannot be upheld, because our results clearly show that the net CSF formation does not take place inside the other brain ventricles and that CSF does not circulate as a slow river from the ventricles to the subarachnoid space.
It is very well known (and commonly applied in routine clinical practice) that the increase of blood osmolality can decrease the CSF (intracranial) pressure, simply by extraction of fluid from nervous tissue. Our experimental results clearly revealed that the increase in CSF osmolality will subsequently lead to the increase of the CSF volume inside the brain ventricles. This drives to a conclusion that the osmolality represents one of the major determinants of fluid exchange in intracranial pressure. It seems that the control of the CSF volume is under the influence of hydrostatic and osmotic forces between the CSF system and the surrounding tissue and that the CSF volume will be changed, depending on the prevalence of those forces, caused by (patho)physiological reasons inside or outside the CSF system. Anyhow, the results presented in this article call for a new approach to the physiology and pathology of CSF and we feel that time has come to re-evaluate the classical hypothesis of the CSF hydrodynamics to abandon this hypothesis as the traditional framework of thinking.
-Legendre R, Piéron H. De la propriété hypnotoxique des humeurs développée au cours d'une veille prolongée C.R. Société de Biologie de Paris 1912; 70; 210-212
-Bouyssou M, Tricoire J Experimental detection of a cervical arousal mechanism of yawning, enhancing intracerebral (CSF) fluid pressure J Dental Res 1985; 64; 721
 -Lepp FH Remarques sur la signification physiologique du bâillement Bull Group Int Rech Sci Stomtol Odontol 1982; 25; 251-290
-Nolman B Yawning, cerebral fluid and the lymphatic pump 2006
-Oreskovic D; Klarica M; Vukic M The formation and circulation of cerebrospinal fluid inside the cat brain ventricles : a fact or an illusion ? Neuroscience letters 2002; 327; 103-106
-Patra P, Gunness TK, Robert R Physiologic variations of the internal jugular vein surface, role of the omohyoid muscle, a preliminary echographic study Surg Radiol Anat 1988; 10; 2; 107-12
-Schniter E The evolution of yawning : why do we yawn and why is it contagious ? thèse 2001
-Schroth G, Klose U Cerebrospinal fluid flow; Physiology of respiration-related pulsations. Neuroradiology 1992; 35; 1; 10-15
-Walusinski O Prostaglandines, adénosine, sommeil & bâillements 2004
-Woodbury R, B Abretj Influence of dying gasps, yawns and sighs on blood pressure and blood flow Am J Physiol 1944; 142; 721-726