Probing the Glymphatic System Using Optical Imaging and Mathematical Modeling

The glymphatic system is a macroscopic waste clearance pathway in the central nervous system (CNS), crucial to maintaining neural homeostasis through the exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF). Impairments in this system have been associated with neurodegenerative diseases such as Alzheimer’s and Parkinson’s, emphasizing the need to understand and potentially improve glymphatic clearance. We investigate tracer diffusion and transport in the glymphatic system by combining optical imaging in rats and mathematical modeling using a partial differential equation of advection-diffusion type. The experimental conditions differ in the levels of isoflurane-induced anesthesia (1.5, 2 and 3%) and the molecular weight of the tracer compounds (1 and 160 kDa). The optimal parameters show a close clustering of the diffusion coefficients and a wider spread of the flow velocities of the cerebrospinal fluid. Our work contributes to a better understanding of flow processes in the brain parenchyma during sleep.