Vacuolar transcellular channels as a drainage pathway for cerebrospinal fluid

1. Based on our ultrastructural investigations in monkeys, we report here a new concept as to the physiological mechanism of drainage of cerebrospinal fluid (c.s.f.) which would seem to bridge the gap between the two apparently opposing views of ;closed' and ;open' system.2. Our studies reveal the presence of an intact mesothelial lining of the arachnoid mater, including its villus-like projections and herniations into the dural sinus and its lacunae, adjacent cells being joined by tight junctions; in addition we have observed for the first time that many lining cells in the region of the superior sagittal sinus are characterized by unit membrane-bound, electron-optically empty giant vacuoles of several micrometres diameter. In one monkey with a fresh subarachnoid haemorrhage, many vacuoles were filled with plasma proteins and some contained intact blood corpuscles.3. Serial section analysis showed that the vacuoles were in fact invaginations from the basal aspect of the cell surface and were evidently in direct communication with the c.s.f. in the subarachnoid space. Some vacuoles in addition showed openings on their apical surface thus constituting transcellular channels or pores. Basal openings up to 3.5 mum and apical openings up to 2.3 mum were seen.4. It is postulated that vacuoles are stages in the formation of a dynamic system of transcellular pores which allow the bulk outflow of c.s.f. down a pressure gradient, and that the mesothelial vacuolation cycle, in providing the requisite number of transcellular pores across the mesothelial barrier at any time, is a controlling factor in the outflow of c.s.f. and in the maintenance of its fluid-pressure within the subarachnoid space.5. The basic similarity between the bulk flow of the aqueous humour and c.s.f. from the anatomically closed cavities of the anterior chamber and the subarachnoid space, respectively, is underlined.6. The present study provides further support for our hypothesis that the bulk outflow of fluid, via a dynamic system of transcellular pores formed by gradually enlarging membranous surface infoldings in a single cell, termed as giant vacuoles, is a fundamental biological process not hitherto described.