Elsevier

Brain Research Bulletin

Volume 77, Issue 6, 16 December 2008, Pages 327-334
Brain Research Bulletin

Review
Cerebrospinal fluid outflow: An evolving perspective

https://doi.org/10.1016/j.brainresbull.2008.08.009Get rights and content

Abstract

Cerebrospinal fluid (CSF) serves numerous important functions in the central nervous system. Despite numerous reports characterizing CSF and its circulation in the subarachnoid space, our understanding of CSF outflow remains limited. Although initial work suggested that both arachnoid granulations and lymphatic capillaries shared in the role of CSF outflow, predominant work since then has focused on the arachnoid granulations. A growing body of recent evidence not only suggests the importance of both arachnoid granulations and lymphatic capillaries, but also additional contributions through transependymal passage likely share in the role of CSF outflow. Consideration of all mechanisms and pathways will help us to better understand the significance of CSF outflow, in health and disease. Here we review how the present concept of CSF outflow has evolved, including a historical review of significant findings and a discussion of the latest innovative developments.

Section snippets

Introduction to cerebrospinal fluid

Cerebrospinal fluid (CSF) is a clear, bright fluid circulating through the subarachnoid space and providing a neuroprotective function as a hydraulic cushion for the brain and spinal cord. It likely also serves metabolic, nutritional, immunologic, and scavenging functions for the central nervous system. CSF is produced primarily in the choroid plexuses of the cerebral ventricles, flows through the subarachnoid space, and eventually returns to the venous system.

Despite an extensive CSF

Transependymal contributions to cerebrospinal fluid drainage

Among the surprising benefits of the clinical application of magnetic resonance imaging (MRI) was the revelation of “water” passage into the periventricular tissues of the intact brain, under high intraventricular pressure. Neuroimaging of patients with ventricular obstruction, and even with idiopathic intracranial hypertension, showed the MRI signal indicative of transependymal passage of CSF. Increased intracranial pressure forces cerebrospinal fluid across the ependymal barrier and into the

Discussion

Current information about the multiple possibilities for CSF outflow in other species suggests that we consider the potential for similar pathways in man. Although most of us know of the traditional AG pathway, fewer of us are as familiar with the major alternative route through the anterior cranial base, especially that via the olfactory channels into the nasopharyngeal lymphatics.

The arachnoid granulations have been studied extensively, but our understanding of their role in CSF outflow

Conflict of interest

Authors confirm that the present manuscript complies with ethical standards and we declare no conflicts of interest exist.

Acknowledgements

The authors are thankful to the Ohio Lions Eye Research Foundation, the Davis Medical Research Grant, and the Fight for Sight Research Awards Program for supporting this research.

References (56)

  • J.F. Alksne et al.

    Functional ultrastructure of the arachnoid villus

    Arch. Neurol.

    (1972)
  • W. Arnold et al.

    Qualitative study of the connections of the subarachnoid space with the lymphatic system of the head and neck

    Acta Otolaryngol.

    (1972)
  • M.E. Bastin et al.

    Diffuse brain oedema in idiopathic intracranial hypertension: a quantitative magnetic resonance imaging study

    J. Neurol. Neurosurg. Psychiatry

    (2003)
  • J. Benito-Leon et al.

    Intracranial hypertension syndrome as an unusual form of presentation of spinal subarachnoid hemorrhage and subdural haematoma

    Acta Neurochir. (Wien)

    (1997)
  • M. Boulton et al.

    Raised intracranial pressure increases CSF drainage through arachnoid villi and extracranial lymphatics

    Am. J. Physiol.

    (1998)
  • M. Boulton et al.

    Drainage of CSF through lymphatic pathways and arachnoid villi in sheep: measurement of 125 I-albumin clearance

    Neuropathol. Appl. Neurobiol.

    (1996)
  • M.W.B. Bradbury et al.

    The role of the lymphatic system in drainage of cerebrospinal fluid and aqueous humour

    J. Physiol.

    (1980)
  • J.B. Brierley et al.

    The connexions of the spinal sub-arachnoid space with the lymphatic system

    J. Anat.

    (1948)
  • T. Brinker et al.

    Dynamic properties of lymphatic pathways for the absorption of cerebrospinal fluid

    Acta Neuropathol.

    (1997)
  • T. Brinker et al.

    Acute changes in the dynamics of the cerebrospinal fluid system during experimental subarachnoid hemorrhage

    Neurosurgery

    (1990)
  • F.C. Courtice et al.

    The removal of protein from the subarachnoid space

    Aust. J. Exp. Biol. Med. Sci.

    (1951)
  • A. Czerniawska

    Experimental investigations on the penetration of 198Au from nasal mucous membrane into cerebrospinal fluid

    Acta Otolaryngol.

    (1970)
  • D. D’Avella et al.

    Scanning electron microscope study of human arachnoid villi

    J. Neurosurg.

    (1983)
  • W.M. Faber

    The nasal mucosa and the subarachnoid space

    Am. J. Anat.

    (1937)
  • P. Gideon et al.

    Increased brain water self-diffusion in patients with idiopathic intracranial hypertension

    AJNR Am. J. Neuroradiol.

    (1995)
  • P. Gideon et al.

    Increased self-diffusion of brain water in hydrocephalus measured by MR imaging

    Acta Radiol.

    (1994)
  • D.M. Grzybowski et al.

    Human arachnoid granulations Part I: a technique for quantifying area and distribution on the superior surface of the cerebral cortex

    Cerebrospinal Fluid Res.

    (2007)
  • D.M. Grzybowski et al.

    In vitro model of cerebrospinal fluid outflow through human arachnoid granulations

    Invest. Ophthalmol. Vis. Sci.

    (2006)
  • P.W. Hanlo et al.

    The effect of intracranial pressure on myelination and the relationship with neurodevelopment in infantile hydrocephalus

    Dev. Med. Child Neurol.

    (1997)
  • D.W. Holman, D.M. Grzybowski, The Effect of Vitamin A on Cultured Arachnoid Granulation Cells: Implications for...
  • D. Horoshovski et al.

    Pseudotumour cerebri in SLE

    Clin. Rheumatol.

    (1997)
  • R.T. Jackson et al.

    Subarachnoid space of the CNS, nasal mucosa, and lymphatic system

    Arch. Otolaryngol.

    (1979)
  • M. Johnston et al.

    Cerebrospinal fluid transport: a lymphatic perspective

    News Physiol. Sci.

    (2002)
  • U. Kelkenberg et al.

    Chicken arachnoid granulations: a new model for cerebrospinal fluid absorption in man

    Neuroreport

    (2001)
  • G. Key et al.

    Studien in der Anatomie des Nervensystems und des Bindesgewebe

    (1876)
  • S. Kida et al.

    Cerebrospinal fluid drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology, and immunological significance

    Neuropathol. Appl. Neurobiol.

    (1993)
  • S. Kida et al.

    A light and electron microscopic and immunohistochemical study of human arachnoid villi

    J. Neurosurg.

    (1988)
  • M. Koskiniemi et al.

    Acute central nervous system complications in varicella zoster virus infections

    J. Clin. Virol.

    (2002)

    • Cited by (0)

    View full text
    Copyright © 2008 Elsevier Inc. All rights reserved.