Study of cerebrospinal fluid flow dynamics in TGF-β1 induced chronic hydrocephalic mice

In a previous study, we found that the CSF level of transforming growth factor beta 1 (TGF-beta 1) is elevated following subarachnoid hemorrhage (SAH) in patients who later develop communicating hydrocephalus, while in mice, an intrathecal injection of TGF-beta 1 can induce communicating hydrocephalus. Recently, histopathological changes in the leptomeninges were studied using the above TGF-beta 1 induced mice model of hydrocephalus. In the present study, in order to further clarify the ventricular dilatation mechanism, we examined cerebrospinal fluid (CSF) flow dynamics in TGF-beta 1 induced hydrocephalic mice. To assess CSF flow, Indian ink was injected into the passage pathway and the time taken for the ink to pass from the parietal intrameningeal CSF space to cervical lymph nodes was determined. The ink study revealed a significant lengthening of the ink passage time due to altered CSF flow dynamics, while a histological examination showed ink stasis in the altered leptomeningeal CSF space compared to PBS injected control mice. TGF-beta 1 induced increased cellularity in the leptomeninx and fibrosis, and a subsequent narrowing of the intrameningeal CSF space. This narrowing causes a disturbance in CSF flow thus generating a mild pressure gradient, which ultimately leads to the development of slowly progressive ventricular dilatation. After SAH, elevated TGF-beta 1 in the CSF may play a similar role, in concert with other factors, in the development of communicating hydrocephalus in human.