Disturbed spatial learning of rats after intraventricular administration of transforming growth factor-β1

Patients with subarachnoid hemorrhage (SAH) who later suffer hydrocephalus show persistently high levels of transforming growth factor-beta1 (TGF-beta1) in the cerebrospinal fluid after the onset of SAH. Recombinant TGF-beta1 induces hydrocephalus in mice. This study examined the spatial learning ability of rats after intraventricular administration of TGF-beta1. Thirteen-week-old Wistar rats were treated with 0.8 or 8.0 mug of human recombinant TGF-beta1 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-beta1-treated groups clearly exhibited impaired spatial learning ability, but they did not exhibit ventricular dilation. Histological examination revealed subarachnoid fibrosis and deactivation of Na+,KT-ATPase in the arachnoid cells. These findings are similar to those of our previous experiments involving injection of TGF-beta1 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.