Water exchange across the blood-CSF barrier: A systematic review

Interest in cerebrospinal fluid (CSF) physiology and its relevance to neurological disease has increased markedly in recent years. Classical descriptions portray CSF as a unidirectional flow from the choroid plexus to the dural venous sinuses and rarely distinguish between its solutes and the solvent (water) component, which constitutes ~99% of CSF. We conducted a systematic literature review to evaluate current evidence for water exchange between CSF and blood across the blood-CSF barriers (BCSFB). Eighteen studies met the inclusion criteria: 15 in experimental animals and six with humans, spanning more than 70 years and employing diverse methodologies. This literature review shows that CSF water moves freely and bidirectionally between CSF and blood across multiple BCSFB sites along the craniospinal axis, including the choroid plexus, ependymal surfaces, pial vessels, and perivascular spaces. The net direction of movement varies locally with hydrostatic, osmotic, and molecular gradients that transiently favor either inflow or outflow. Blood-CSF water exchange occurs predominantly by diffusion and is modulated by aquaporins and local vascular forces. These findings challenge the classical concept of unidirectional CSF production and absorption, supporting instead a dynamic equilibrium where distributed, gradient-driven water flux maintains brain water homeostasis.