Assessing Fluid Flow through Brain Tissue using a Mouse Model

Cerebrospinal fluid (CSF) transport through the glymphatic system is critical for clearing metabolic waste from the brain, and disruptions in this process are increasingly linked to neurodegeneration. CSF flows along arteries via perivascular spaces (PVSs) into brain tissue, facilitating waste clearance. While bulk CSF flow along PVSs is well understood through imaging and modeling, the dominant mechanism driving solute movement from PVSs into brain tissue is debated: Is solute transport due to diffusion alone or by a combination of diffusion plus advection? To investigate this, we characterized solute transport near the cortical surface in mice. We injected fluorescent dye into the CSF and recorded time-lapse epifluorescence images through the skull. Profiles of pixel intensity transverse to cerebral arteries were compared to predictions from models of diffusion-only transport and diffusion plus advection. We also consider anatomical uncertainties near the cortical surface, including potential contributions from superficial CSF layers. This experiment may help refine the definition of solute movement in the brain and provide a background for future therapeutic strategies targeting glymphatic clearance.