There were early suggestions that movements of large molecules between the parenchyma and CSF could be faster than seen in Cserr’s work. The first of these was the work of Wagner [68] followed by Rennels et al. [69, 135] on entry and exit of horseradish peroxidase. Within an hour of being added to CSF, it could be seen outlining blood vessels deep in the parenchyma. Somewhat later Shibata et al. [62] found that the half-life of inulin was shorter than expected and Groothuis et al. [131] found that when rats were anaesthetized with barbiturates the half-life for sucrose was as Cserr had seen with albumin, but when animals were either awake or anaesthetized with ketamine/zylazine the half-life was much shorter (see Table 1).