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Am J Physiol Regul Integr Comp Physiol 277: R263-R271, 1999;
0363-6119/99 $5.00
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Vol. 277, Issue 1, R263-R271, July 1999

Altered formation and bulk absorption of cerebrospinal fluid in FGF-2-induced hydrocephalus

C. E. Johanson1, J. Szmydynger-Chodobska1, A. Chodobski1, A. Baird2, P. McMillan3, and E. G. Stopa3

Program in Neurosurgery, Departments of 1 Clinical Neurosciences and 3 Pathology, Brown University/Rhode Island Hospital, Providence, Rhode Island 02903; and 2 Ciblex Corporation, San Diego, California 92121

Upregulation of certain growth factors in the central nervous system can alter brain fluid dynamics. Hydrocephalus was produced in adult Sprague-Dawley rats by infusing recombinant basic fibroblast growth factor (FGF-2) at 1 µg/day into a lateral ventricle for 2, 3, 5, or 10-12 days. Lateral and third ventricular enlargement progressively increased from 2 to 10 days. Ventriculomegaly was also induced by a 75% reduced dose of FGF-2. At 10-12 days, there was a 29% attenuation in cerebrospinal fluid (CSF) formation rate, from 2.5 to 1.8 µl/min (P < 0.01). Choroid plexus, the main site of CSF secretion, had an augmented number of dark epithelial cells, which have previously been associated with decreased choroidal fluid formation. The twofold elevated resistance to CSF absorption, i.e., 0.8 to 1.7 mmHg · min-1 · µl-1, was attributable, at least in part, to enhanced fibrosis and collagen deposits in the arachnoid villi, a major site for CSF absorption. Normal CSF pressure (2-3 mmHg) was consistent with a patent cerebral aqueduct and reduced CSF formation rate. The FGF-2-induced ventriculomegaly is interpreted as an ex vacuuo hydrocephalus brought about by an altered neuropil and interstitium of the brain.

intracranial pressure; growth factors; fluid dynamics; ventriculomegaly; normal-pressure hydrocephalus; extracellular matrix; neuroendocrine regulation ; fibroblast growth factor


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