Background and purpose: According to the classical hypothesis, the cerebrospinal fluid (CSF) is actively secreted inside the brain's ventricular system, predominantly by the choroid plexuses, before flowing unidirectionally in a cranio-caudal orientation toward the arachnoid granulations (AGs), where it is reabsorbed into the dural venous sinuses. This concept has been accepted as a doctrine for more than 100 years and was subjected only to minor modifications. Its inability to provide an adequate explanation to questions arising from the everyday clinical practice, in addition to the ever growing pool of experimental data contradicting it, has led to the identification of its limitations. Literature includes an increasing number of studies suggesting a more complex mechanism than that previously described. This review article summarizes the proposed mechanisms of CSF regulation, referring to the key clinical and experimental developments supporting or defying them.
Methods: A non-systematical literature search of the major databases was performed for studies on the mechanisms of CSF homeostasis. Gray literature was additionally assessed employing a hand-search technique. No restrictions were imposed regarding the time, language, or type of publication.
Conclusion: CSF secretion and absorption are expected to take place throughout the entire brain's capillaries network under the regulation of hydrostatic and osmotic gradients. The unidirectional flow is defied, highlighting the possibility of its complete absence. The importance of AGs is brought into question, potentiating the significance of the lymphatic system as the primary site of reabsorption. However, the definition of hydrocephalus and its treatment strategies remain strongly associated with the classical hypothesis.
Keywords: Bulat Klarica Oreskovic hypothesis; Cerebrospinal fluid; Hydrocephalus; Pathophysiology; Weed Dandy Cushing hypothesis.
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