Quantifying the relationship between spreading depolarization and perivascular cerebrospinal fluid flow.

Recent studies have linked spreading depolarization (SD, an electro-chemical wave in the brain following stroke, migraine, traumatic brain injury, and more) with increase in cerebrospinal fluid (CSF) flow through the perivascular spaces (PVSs, annular channels lining the brain vasculature). We develop a novel computational model that couples SD and CSF flow. We first use high order numerical simulations to solve a system of physiologically realistic reaction-diffusion equations which govern the spatiotemporal dynamics of ions in the extracellular and intracellular spaces of the brain cortex during SD. We then couple the SD wave with a 1D CSF flow model that captures the change in cross-sectional area, pressure, and volume flow rate through the PVSs. The coupling is modelled using an empirical relationship between the excess potassium ion concentration in the extracellular space following SD and the vessel radius. We find that the CSF volumetric flow rate depends intricately on the length and width of the PVS, as well as the vessel radius and the angle of incidence of the SD wave. We derive analytical expressions for pressure and volumetric flow rates of CSF through the PVS for a given SD wave and quantify CSF flow variations when two SD waves collide. Our numerical approach is very general and could be extended in the future to obtain novel, quantitative insights into how CSF flow in the brain couples with slow waves, functional hyperemia, seizures, or externally applied neural stimulations.