To study the clearance of 14C-inulin from the rat brain, we consider 3 model variations.
We first assume that the bulk flow of fluid in the interstitial space is negligible and transport occurs only due to diffusion in the interstitial space. Hence, we useEq (1) . Clearance of 14C-inulin occurs at the brain surface and is modelled by appropriate boundary conditions described below. This scenario is represented by Test case 1 on Fig 1 .
Secondly, we consider a clearance of 14C-inulin due to the glymphatic system. Hence, we use System (3 ) with |J| = 4 compartments: ECS, PVS around arteries, PVS around capillaries, and PVS around veins. Test case 2 in Fig 1 depicts this scenario. CSF is assumed to flow from the PVS around arteries to the PVS around capillaries or in the ECS. From the PVS around capillaries, CSF flows to the ECS or the PVS around veins. From the ECS, CSF may be reabsorbed in the PVS around veins or capillaries. Clearance from the brain may occur at the brain surface from the ECS, the PVS around veins and the PVS around arteries.
Thirdly, we add the effect of blood vasculature. Indeed, cerebral blood vessels are not impermeable, and some fluid could leak from them to the other structures [38 (link)]. This case is depicted by Test case 3 inFig 1 .
For the sake of clarity, in the following, we refer to these 3 applications of our modelling framework as
We first assume that the bulk flow of fluid in the interstitial space is negligible and transport occurs only due to diffusion in the interstitial space. Hence, we use
Secondly, we consider a clearance of 14C-inulin due to the glymphatic system. Hence, we use System (
Thirdly, we add the effect of blood vasculature. Indeed, cerebral blood vessels are not impermeable, and some fluid could leak from them to the other structures [38 (link)]. This case is depicted by Test case 3 in
For the sake of clarity, in the following, we refer to these 3 applications of our modelling framework as
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