A holistic multi-scale mathematical model of the murine extracellular fluid systems and study of the brain interactive dynamics

Venue: Reading Room Hall PovoZero – Via Sommarive, 14 Povo - Trento
Hour: 15.00

• Christian Contarino - PhD in Mathematics

Abstract:
Recent advances in medical science regarding the interaction and functional role of fluid compartments in the central nervous system have attracted the attention of many researchers across various disciplines. Neurotoxins are constantly cleared from the brain parenchyma through the intramural periarterial drainage system, glymphatic system and meningeal lymphatic system. Impairment of these systems can potentially contribute to the onset of neurological disorders.
The goal of this talk is to contribute to the understanding of brain fluid dynamics and to the role of vascular pathologies in the context of neurological disorders. To achieve this goal, we designed the first multi-scale, closed-loop mathematical model of the murine fluid system, incorporating: heart dynamics, major arteries and veins, microcirculation, pulmonary circulation, venous valves, cerebrospinal fluid (CSF), brain interstitial fluid (ISF), Starling resistors, Monro-Kellie hypothesis, brain lymphatic drainage and the modern concept of CSF/ISF drainage and absorption based on the Bulat-Klarica-Orešković hypothesis. The computational results are validated against magnetic resonance flow measurements, in-vivo intracranial pressure waveforms acquired in healthy mice and in mice with impairment of the intracranial venous outflow. Through a systematic use of our computational model, we propose a hypothesis on the working principles of the glymphatic system and we show how impairment of the cerebral venous outflow might potentially lead to accumulation of solutes in the parenchyma, by altering CSF and ISF dynamics.

Supervisor: Eleuterio Francisco Toro