Headway For Hydrocephalus: When Cerebrospinal Fluid Can't Go With The Flow

Main Category: Hypertension
Article Date: 07 Jul 2006 - 8:00 PDT

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Hydrocephalus occurs when there is an abnormal accumulation of cerebrospinal fluid (CSF) in the brain, usually due to a blockage of CSF outflow. In a study appearing in the July issue of the Journal of Clinical Investigation, Sanbing Shen and colleagues from the University of Aberdeen uncover how CSF flow is regulated throughout the brain.

The Sylvian aqueduct is a canal between two cavities of the brain, through which CSF passes. In most vertebrate species, a gland (known as the subcommissural organ or SCO) at the entrance to this canal secretes glycoproteins that form a long, thread-like structure known as Reissner's fiber. This fiber extends through the aqueduct and prevents its closure, thereby ensuring continuous CSF flow. Microscopic hair-like structures known as cilia cover the surface of cells in the aqueduct and also help maintain CSF flow. Shen and colleagues examined mice overexpressing the human PAC1 receptor, which binds the neurotransmitter PACAP, on the surface of SCO cells. These animals developed hydrocephalus-like characteristics and possessed fewer cells in the SCO, which may result in disorganization or absence of Reissner's fiber. In addition, shorter, inefficient cilia were observed on the cells lining the aqueduct. Together, these changes likely result in turbulent CSF flow at the aqueduct entrance and reduced flow within the cerebral aqueduct, promoting hydrocephalus. In an accompanying commentary, David Picketts from the University of Ottawa discusses the novel role for this signaling cascade in the regulation of CSF circulation.

TITLE: Expression of the human PAC1 receptor leads to dose-dependent hydrocephalus-related abnormalities in mice

AUTHOR CONTACT:
Sanbing Shen
University of Aberdeen, Aberdeen, United Kingdom.
E-mail: sanbing.shen@abdn.ac.uk.

View the PDF of this article at: http://https://www.the-jci.org/article.php?id=27597 ACCOMPANYING COMMENTARY

TITLE: Neuropeptide signaling and hydrocephalus: SCO with the flow

AUTHOR CONTACT:
David J. Picketts
University of Ottawa, Ontario, Canada.
Email: dpicketts@ohri.ca.

View the PDF of this article at: http://https://www.the-jci.org/article.php?id=29148

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JCI table of contents: July 3, 2006
Contact: Brooke Grindlinger
Journal of Clinical Investigation

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