Stephen Prouxl

Theodor Kocher Institute, University of Bern

Title: A bulk flow of cerebrospinal fluid from the ventricles to the lymphatic system (not to the brain)

Abstract: The pathways of circulation and clearance of cerebrospinal fluid (CSF) are currently a controversial topic. We have found using injections of inert macromolecular tracers into the lateral ventricle or cisterna magna of mice that a bulk flow of tracers proceeds through the basal cisterns to the lymphatic outflow pathways from the skull (Ma et al., Nat Commun, 2017). Consistent with previous work, CSF outflow pathways were found to occur at the exit points of cranial nerves (e.g. olfactory or optic nerves) to reach lymphatic vessels that tracked to deep cervical and mandibular lymph nodes. A lesser outflow of tracer to lymphatic vessels was also found to occur at the sacral end of the spine (Ma et al, J Exp Med, 2019). Therefore, we have proposed the concept that turnover of CSF occurs through lymphatic vessels rather than through arachnoid villi to dural venous sinuses. Furthermore, we found that this fluid turnover is dramatically increased when the mice are awake and active and that a convective flow to the brain parenchyma under in vivo conditions could not be detected, in opposition to the “glymphatic” concept of an influx of CSF along paravascular spaces of arteries (Ma et al., Acta Neuropath, 2019).

Literature
Ma, Q., B.V. Ineichen, M. Detmar, and S.T. Proulx. 2017. Outflow of cere- brospinal fluid is predominantly through lymphatic vessels and is re- duced in aged mice. Nat. Commun. 8:1434
Ma, Q., M. Ries, Y. Decker, A. Müller, C. Riner, A. Bücker, K. Fassbender, M. Detmar, and S.T. Proulx. 2019. Rapid lymphatic efflux limits cerebro- spinal fluid flow to the brain. Acta Neuropathol. 137:151–165.
Ma, Q., Decker, Y., Müller, A., Ineichen, B. V. & Proulx, S. T. 2019. Clearance of cerebrospinal fluid from the sacral spine through lymphatic vessels. J Exp Med, jem.20190351