• Darko Orešković, Milan Radoš, and Marijan Klarica.
• Ruđer Bošković Institute, Department of Molecular Biology, Zagreb, Croatia. Electronic address: doresk@irb.hr.
• Neuroscience. 2017 Jun 23; 354: 69-87.

AbstractThe classic hypothesis presents the cerebrospinal fluid (CSF) as the "third circulation," which flows from the brain ventricles through the entire CSF system to the cortical subarachnoid space to eventually be passively absorbed into the superior sagittal sinus through arachnoid granulations. The choroid plexus (CP) represents a key organ in the classic CSF physiology and a powerful biological pump, which exclusively secretes CSF. Thereby, the CP is considered to be responsible for CSF pressure regulation and hydrocephalus development. This article thoroughly analyzes the role of the CP in the CSF dynamics, presenting arguments in favor of the thesis that the CPs are neither biological pumps nor the main site of CSF secretion; that they do not participate in regulation of ICP/CSF pressure; are not the reason for the existence of hydrostatic pressure gradient in the CSF system and that this gradient is not permanent (disappeared in the horizontal position); and that they do not generate imagined unidirectional CSF circulation, hydrocephalus development and increased ICP/CSF pressure. The classic hypothesis cannot provide an explanation for these controversies but the recently formulated Bulat-Klarica-Orešković hypothesis can. According to this hypothesis, CSF production and absorption (CSF exchange) are constant and present everywhere in the CSF system, and although the CSF is partially produced by the CP, it is mainly formed as a consequence of water filtration between the capillaries and interstitial fluid.Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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