title: How astrocyte networks may contribute to cerebral metabolite clearance.
abstract: The brain possesses an intricate network of interconnected fluid pathways that are vital to the maintenance of its homeostasis. With diffusion being the main mode of solute transport in cerebral tissue, it is not clear how bulk flow through these pathways is involved in the removal of metabolites. In this computational study, we show that networks of astrocytes may contribute to the passage of solutes between tissue and paravascular spaces (PVS) by serving as low resistance pathways to bulk water flow. The astrocyte networks are connected through aquaporin-4 (AQP4) water channels with a parallel, extracellular route carrying metabolites. Inhibition of the intracellular route by deletion of AQP4 causes a reduction of bulk flow between tissue and PVS, leading to reduced metabolite clearance into the venous PVS or, as observed in animal studies, a reduction of tracer influx from arterial PVS into the brain tissue.
authors.affiliation: The Interface Group, Institute of Physiology, University of Zurich, Zurich, Switzerland.|Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Asgari
authors.affiliation: The Interface Group, Institute of Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Diane
authors.initials: D
authors.lastname: de Zélicourt
authors.affiliation: The Interface Group, Institute of Physiology, University of Zurich, Zurich, Switzerland.|Neuroscience Center Zurich, University of Zurich, Zurich, Switzerland.|Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Vartan
authors.initials: V
authors.lastname: Kurtcuoglu
mesh_terms: D051401:Aquaporin 4 / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism*; D001834:Body Water / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D003198:Computer Simulation; D015640:Ion Channel Gating / Q000502:physiology; D008657:Metabolic Clearance Rate; D008959:Models, Neurological; D009415:Nerve Net / Q000378:metabolism*
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4