Disturbed spatial learning of rats after intraventricular administration of transforming growth factor-beta 1.
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.
Nakazato
Fumi
F
Department of Neurosurgery, Shinshu University School of Medicine, Matsumoto, Nagano. tadatsu@hsp.md.shinshu-u.ac.jp
Tada
Tsuyoshi
T
Sekiguchi
Yasuyuki
Y
Murakami
Kentaro
K
Yanagisawa
Shin
S
Tanaka
Yuichiro
Y
Hongo
Kazuhiro
K
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
C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1