RAPID DISTRIBUTION OF INTRAVENTRICULARLY ADMINISTERED SUCROSE INTO CEREBROSPINAL-FLUID CISTERNS VIA SUBARACHNOID VELAE IN RAT

The intracranial distribution of [C-14]sucrose, an extracellular marke r infused for 30 s into one lateral ventricle, was determined by autor adiography of frozen-dried brain sections. Within 3.5 min [C-14]sucros e appeared in: (i) the third ventricle, including optic, infundibular and mammillary recesses; (ii) the aqueduct of Sylvius; (iii) the velum interpositum, a part of the subarachnoid space that runs along the ro of of the third ventricle and contains many blood vessels; (iv) the me sencephalic and fourth ventricles; and (v) the superior medullary velu m, a highly vascular extension of the subarachnoid space that terminat es at the walls of the mesencephalic and fourth ventricles. Within 5 m in, radioactivity was present in the interpeduncular, ambient and quad rigeminal cisterns, which encircle the midbrain. By 10 min, approximat ely 11% of the radioactivity had passed into the subarachnoid space vi a a previously undescribed flow pathway that included the velum interp ositum and superior medullary velum. At many places along the ventricu lar system, [C-14]sucrose appeared to move from cerebrospinal fluid in to the adjacent tissue by simple diffusion, as reported previously (Bl asberg R. G. et al. (1974) J. Pharmac. exp. Ther. 195, 73-83; Levin V. A. et al. (1970) Am. J. Physiol. 219, 1528-1533; Patlak C. and Fenste rmacher J. D. (1975) Am. J. Physiol. 229, 877-884; Rosenberg G. A. and Kyner W. T. (1980) Brain Res. 193, 56-66; Rosenberg G. A. et al. (198 6) Am. J. Physiol. 251, F485-F489). Little sucrose was, however, taken up by: (i) circumventricular organs such as the subfornical organ; (i i) medullary and cerebellar tissue next to the lateral recesses; and ( iii) the superior and inferior colliculi and cerebral peduncles. For t he latter two groups of structures, entry from cerebrospinal fluid was apparently blocked by a thick, multilayered glia limitans. Although [ C-14]sucrose was virtually absent from the rest of the subarachnoid sy stem after 1 h, it remained in the perivascular spaces and/or walls of pial arteries and arterioles for more than 3 h. Certain transport pro teins, protease inhibitors, growth factors and other neurobiologically active materials are present in cerebrospinal fluid, and their distri bution to the brain and its blood vessels may be important. The presen t work shows, in the rat, that the flow of cerebrospinal fluid and the disposition of its constituents is fairly complex and differs among r egions. Flow was rapid throughout the ventricular system and into vari ous subarachnoid velae and cisterns, but was surprisingly slow and sli ght over the cerebral and cerebellar cortices. The cerebrospinal fluid -to-tissue flux of material was relatively free at many interfaces, bu t was greatly restricted at others, the latter indicating that the old concept of a ''cerebrospinal fluid-brain barrier'' may hold at such p laces. Finally, radiolabeled sucrose was retained longer within the wa lls and perivascular spaces of pial arteries and arterioles than in ot her subarachnoid tissues; one function of the cerebrospinal fluid syst em or ''third circulation'' may thus be delivering factors and agents to these pial blood vessels. Copyright (C) 1996 IBRO. Published by Els evier Science Ltd.