The last decade has seen a tremendous increase in research probing the role of cerebrospinal fluid (CSF) circulation through the brain in health and disease. This circulation, known as the “glymphatic” (glial-lymphatic) system, is a novel transport pathway first described in 2012 which plays an important role in removing protein waste from the brain. Amyloid-beta is one such protein waste that is known to accumulate over decades, contributing to the development of neurodegenerative diseases, including Alzheimer’s. I will first give a brief history of this field, then discuss several important open questions, including what propels CSF circulation and why it decreases with aging. I will present recent numerical modeling from my research team that suggests CSF and blood flow work synergistically to amplify brain waste clearance. I will also show that by carefully calibrating our model against published in vivo measurements of amyloid-beta, we obtained critical waste production and clearance parameters not yet measured in experiments. In the last portion of the seminar, I will present preliminary results from in vivo mouse experiments demonstrating how neuromodulation (electrical stimulation of nerves) can be leveraged to enhance glymphatic transport in the brain, potentially leading to therapeutic approaches to prevent or slow progression of Alzheimer’s and other neurodegenerative diseases.
Jeff Tithof, Assistant Professor of Mechanical Engineering, University of Minnesota
Host: Michelle Driscoll
Joan West
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