The model used by Smith and Rapoport ignores exchange of substance between the parenchyma and CSF in the sub-arachnoid spaces, i.e. it ignores perivascular transport. However, for the same reason that backflux from parenchyma to blood does not alter the initial rate of increase in concentration within the parenchyma, loss to CSF will also not alter the initial rate and thus the calculation of PS. However, once concentrations in parenchyma and CSF increase, net perivascular fluxes for Na+ will be comparable to the net fluxes across the blood–brain barrier and thus cannot be ignored in calculations of the time course.