Studies of cerebrospinal fluid flow and penetration into brain following lateral ventricle and cisterna magna injections of the tracer [C-14]inulin in rat

Parasynaptic communication, also termed volume transmission, has been sugge sted as an important means to mediate information transfer within the centr al nervous system. The purpose of the present study was to visualize by aut oradiography the available channels for fluid movement within the extracell ular space following injection of the inert extracellular marker [C-14]inul in into the lateral ventricle or cisterna magna. Bolus injections of 5 mu l of 1 mu Ci of [C-14]inulin were made in awake rats via chronically implant ed cannulae. After survival times ranging from 5 min to 4 h, brains were pr ocessed for in vivo autoradiography. At 5 min the tracer distributed throug hout the ventricles, subarachnoid spaces and cisterns "downstream" of the i njection sites. Penetration into the brain from these sites was complex wit h preferential entry along the ventral side of the brain, especially into t he hypothalamus and brainstem. By 4 h virtually the entire brain was labele d irrespective of the site of tracer application. Sustained tracer entry fr om subarachnoid spaces suggests that some areas act as depots to trap circu lating material. This mechanism may contribute to the pattern of deep penet ration at later time-points. The spatial and temporal characteristics of fl uid movement throughout the brain are instructive in the interpretation of many experimental procedures involving injection of molecules into the cere brospinal fluid (C) 1999 IBRO. Published by Elsevier Science Ltd.