These data suggest a bulk flow of interstitial fluid from the striatum towards the adjacent lateral ventricle. Tracers also entered paravascular spaces around arteries both after injection in the cisterna magna and striatum, but this appeared to be of minor importance. We observed a distribution pattern of tracers from the parenchyma to the ventricular system, from where tracers mixed with the cerebrospinal fluid, reached the subarachnoid space, and left the brain via the cribriform plate and the nose. We subsequently performed confocal fluorescence imaging of horizontal brain sections and made 3D reconstructions of the mouse brain and vasculature. To trace the distribution of interstitial and cerebrospinal fluid in the brain, and to identify the anatomical structures involved, we infused a mix of fluorescent tracers with different sizes into the cisterna magna or striatum of mouse brains. However, the proposed direction of flow, the anatomical structures involved, and the driving forces are controversial.
Suggested mechanisms for clearance implicate a role for brain interstitial and cerebrospinal fluids. In the absence of a true lymphatic system in the brain parenchyma, alternative clearance pathways for excess fluid and waste products have been proposed.
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