title: Disturbed spatial learning of rats after intraventricular administration of transforming growth factor-beta 1.
abstract: Patients with subarachnoid hemorrhage (SAH) who later suffer hydrocephalus show persistently high levels of transforming growth factor-beta 1 (TGF-beta 1) in the cerebrospinal fluid after the onset of SAH. Recombinant TGF-beta 1 induces hydrocephalus in mice. This study examined the spatial learning ability of rats after intraventricular administration of TGF-beta 1. Thirteen-week-old Wistar rats were treated with 0.8 or 8.0 micrograms of human recombinant TGF-beta 1 by direct injection or via osmotic pump. Three months later, their spatial learning ability was evaluated with a Morris water maze. Ventricular size, ultrastructural features, and sodium-potassium-adenosine triphosphatase (Na+, K(+)-ATPase) activity of the subarachnoid space were examined. All three TGF-beta 1-treated groups clearly exhibited impaired spatial learning ability, but they did not exhibit ventricular dilation. Histological examination revealed subarachnoid fibrosis and deactivation of Na+, K(+)-ATPase in the arachnoid cells. These findings are similar to those of our previous experiments involving injection of TGF-beta 1 in mice. The present and previous studies suggest that subarachnoid fibrosis is an important factor in the disturbance of the spatial learning ability of rats, whereas ventricular size is less important.
authors.affiliation: Department of Neurosurgery, Shinshu University School of Medicine, Matsumoto, Nagano. tadatsu@hsp.md.shinshu-u.ac.jp
authors.forename: Fumi
authors.initials: F
authors.lastname: Nakazato
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Tada
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sekiguchi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Murakami
authors.forename: Shin
authors.initials: S
authors.lastname: Yanagisawa
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hongo
mesh_terms: D000818:Animals; D007276:Injections, Intraventricular; D018782:Maze Learning / Q000187:drug effects*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
chemical_list: C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1