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

Upregulation of certain growth factors in the central nervous system can al ter brain fluid dynamics. Hydrocephalus was produced in adult Sprague-Dawle y rats by infusing recombinant basic fibroblast growth factor (FGF-2) at 1 mu g/day into a lateral ventricle for 2, 3, 5, or 10-12 days. Lateral and t hird ventricular enlargement progressively increased from 2 to 10 days. Ven triculomegaly was also induced by a 75% reduced dose of FGF-2. At 10-12 day s, there was a 29% attenuation in cerebrospinal fluid (CSF) formation rate, from 2.5 to 1.8 mu l/min (P < 0.01). Choroid plexus, the main site of CSF secretion, had an augmented number of dark epithelial cells, which have pre viously been associated with decreased choroidal fluid formation. The twofo ld elevated resistance to CSF absorption, i.e., 0.8 to 1.7 mmHg . min(-1).m u l(-1), was attributable, at least in part, to enhanced fibrosis and colla gen deposits in the arachnoid villi, a major site for CSF absorption. Norma l CSF pressure (2-3 mmHg) was consistent with a patent cerebral aqueduct an d reduced CSF formation rate. The FGF-X-induced ventriculomegaly is interpr eted as an ex vacuuo hydrocephalus brought about by an altered neuropil and interstitium of the brain.