Skip to main content
  • Oral presentation
  • Open access
  • Published:

CSF circulation and cerebral cortex development

Over the past decade, studies of a number of CSF conditions, in particular the H-Tx rat and curly tail mouse, have demonstrated a critical role for CSF in the development of the cerebral cortex and, more specifically, in the developmental defect associated with fetal-onset hydrocephalus and neural tube defects. This paper is an attempt to present a CSF hypothesis for CNS and brain development.

CNS development proceeds around a fluid-filled neural tube. The source of fluid within the developing central nervous system changes from an active blood-CSF barrier in the mesencephalon transporting specific proteins and water into the growing fluid cavity and maintaining the osmotic potential of the fluid [13], to a high volume fluid and protein secreting choroid plexus [4]. The fluid volume output changes coincident with a change in fluid pathway from simply filling a sealed tube to bulk flow, reaching a production of 0.3 ml/min in adult brain, forcing fluid though the ventricles and out into and around the subarachnoid space [5]. Moreover the composition changes driving and supporting development of the brain stem and spinal cord and, later, through CSF output, the cerebral cortex [6]. Evidence from in vitro experiments demonstrates that CSF is sufficient to support the viability, proliferation and differentiation of neural stem/progenitor in age dependent manner [7]. Evidence from the curly tail mouse as well as from brain slice experiments demonstrate that CSF passage through the subarachnoid space is required for correct migration and lamination of the cortex with neurons generated in the ventricular zone. Evidence from the hydrocephalic H-Tx rat shows that CSF composition alone can arrest development through a blockade of cell division. This blockade involves abnormal folate handling and has recently been shown to be amenable to treatment through maternal folate supplementation, but not folic acid [8].

Further understanding of the role of CSF in CNS and brain development will help expose many of the missing elements in our understanding of how the CNS develops and how this can go wrong. The future may thus provide treatments to prevent and/or treat conditions of poor development.


  1. Cottingham K: The complex composition of embryonic CSF. J Proteome Res. 2007, 6: 3537-3548. 10.1021/pr070247w.

    Article  Google Scholar 

  2. Parvas M, Parada C, Bueno D: A blood-CSF barrier function controls embryonic CSF protein composition and homeostasis during early CNS development. Dev Biol. 2008, 321: 51-63. 10.1016/j.ydbio.2008.05.552.

    Article  CAS  PubMed  Google Scholar 

  3. Gato A, Desmond ME: Why the embryo still matters: CSF and the neuroepithelium as interdependent regulators of embryonic brain growth, morphogenesis and histiogenesis. Dev Biol. 2009, 327: 263-272. 10.1016/j.ydbio.2008.12.029.

    Article  CAS  PubMed  Google Scholar 

  4. Johanson CE, Duncan JA, Stopa EG, Baird A: Enhanced prospects for drug delivery and brain targeting by the choroid plexus-CSF route. Pharm Res. 2005, 22: 1011-1037. 10.1007/s11095-005-6039-0.

    Article  CAS  PubMed  Google Scholar 

  5. Pourghasem M, Mashayekhi F, Bannister CM, Miyan J: Changes in the CSF fluid pathways in the developing rat fetus with early onset hydrocephalus. Eur J Pediatr Surg. 2001, 11 (Suppl 1): S10-S13. 10.1055/s-2001-19741.

    Article  PubMed  Google Scholar 

  6. Miyan JA, Nabiyouni M, Zendah M: Development of the brain: a vital role for cerebrospinal fluid. Can J Physiol Pharmacol. 2003, 81: 317-328. 10.1139/y03-027.

    Article  CAS  PubMed  Google Scholar 

  7. Miyan JA, Zendah M, Mashayekhi F, Owen-Lynch PJ: Cerebrospinal fluid supports viability and proliferation of cortical cells in vitro, mirroring in vivo development. Cerebrospinal Fluid Res. 2006, 3: 2-10.1186/1743-8454-3-2.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Cains S, Shepherd A, Nabiuni M, Owen-Lynch PJ, Miyan J: Addressing a folate imbalance in fetal cerebrospinal fluid can decrease the incidence of congenital hydrocephalus. J Neuropathol Exp Neurol. 2009, 68: 404-416. 10.1097/NEN.0b013e31819e64a7.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Jaleel Miyan.

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Cite this article

Miyan, J. CSF circulation and cerebral cortex development. Fluids Barriers CNS 6 (Suppl 2), S13 (2009).

Download citation

  • Published:

  • DOI: