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Rethink the classical view of cerebrospinal fluid production

Nature Reviews Neurology volume 17, page 590 (2021)Cite this article

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In their brilliant review, Joanna Wardlaw and colleagues describe those well-known but poorly understood CNS features, the perivascular spaces (Wardlaw, J. M. et al. Perivascular spaces in the brain: anatomy, physiology, and pathology. Nat. Rev. Neurol. 16, 137–153 (2020)1). Questions persist on the role of these spaces in interstitial fluid–cerebrospinal fluid (ISF–CSF) metabolite clearance, such as drainage pathways, the role of aquaporin 4 in water transport, and the effects of sleep on their function. In their discussion, the authors accurately indicate that the occurrence of CSF drainage via arachnoid granulations in humans has been questioned. We believe that their statement that CSF is “produced continuously in the choroid plexus” should be examined too.

The traditional ‘bulk flow’ theory of active production of CSF in the choroid plexus and its passive absorption via arachnoid granulations — historically presented as the ‘third circulation’ — mostly originates from a single experiment by Dandy published in 1919 that has not been reproduced since. He performed a unilateral choroid plexectomy and obstruction of the foramen of Monro on one dog, which led to the collapse of the plexectomized ventricle and dilation of the ventricle containing a choroid plexus2. By contrast, in 1969, Milhorat et al.3 obstructed the ventricular system of 76 monkeys, which caused hydrocephalus independently of choroid plexectomy, suggesting a role for extra-choroidal sites in CSF production.

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Authors and Affiliations

  1. Department of Neuroradiology, Hôpital Pierre Paul Riquet CHU Purpan, Toulouse, France

    Margaux Roques & Fabrice Bonneville

  2. Department of Neurosurgery, Hôpital Pierre Paul Riquet CHU Purpan, Toulouse, France

    Amaury De Barros

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  1. Margaux Roques
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  2. Amaury De Barros
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  3. Fabrice Bonneville
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Correspondence to Margaux Roques.

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Roques, M., De Barros, A. & Bonneville, F. Rethink the classical view of cerebrospinal fluid production. Nat Rev Neurol 17, 590 (2021). https://doi.org/10.1038/s41582-021-00538-0

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