The hydrology of cerebrospinal fluid flow: Rivulets, fjords, and oceans

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Science Translational Medicine  04 Nov 2015:
Vol. 7, Issue 312, pp. 312ec188
DOI: 10.1126/scitranslmed.aad5504

Similar to a hydrologist measuring water flow across complex terrain, the brain presents numerous interfaces and boundaries that make dynamic fluid modeling a daunting task. The production, partitioning, and drainage of brain interstitial and cerebrospinal fluid is an active area of study. The importance is that brain fluids are involved in clearance of numerous brain waste products, including water itself, which is generated by cells as a metabolic byproduct. In new work, Bedussi et al. used fluorescent tracers to study the directionality of interstitial and cerebrospinal fluid flow following injection into the mouse brain striatum or cisterna magna.

The authors collected 2500 thin sections from each mouse brain and then used automated en face fluorescent imaging and confocal microscopy to create three-dimensional reconstructions. They found that dextran tracers injected into the striatum traversed the ependymal surface and entered the brain ventricles and choroid plexus by convective flow. In addition, tracers injected into the subarachnoid space were able to enter the brain parenchyma, but only to a limited extent. Although cisterna magna tracers did not enter the ventricles or the deep venous drainage system, they were detected in the extracranial nasal lymphatic drainage system, supporting a known role for cerebrospinal fluid drainage along spinal nerves and the cribiform plate.

Although analysis of brain fluid transport is still in its infancy, this new study supports a role for bulk flow to the brain ventricles and for extracranial lymphatic drainage, rather than transit primarily through the paravascular system along intraparenchymal arteries and toward venous outflow tracts. Bedussi et al. describe the point of highest interstitial pressure as a "continental divide" and propose that bulk flow may occur along vessels either toward the brain ventricles or the cortical surface, depending on local brain anatomy. They suggest that the peri- and paravascular spaces are analogous to fjords, allowing fluid transport "from the mountains to the sea." In this analogy, the subarachnoid space is the sea, which can receive injected tracers along vessels as well as deliver them to deeper brain regions. Clearly, there are many routes for clearance of fluids in the mammalian brain, and we are just beginning to explore and understand them.

B. Bedussi et al., Clearance from the mouse brain by convection of interstitial fluid towards the ventricular system. Fluids Barriers CNS 10.1186/s12987-015-0019-5 (2015). [Full Text]

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