Neuroprotective Role of Gap Junctions in a Neuron Astrocyte Network Model

Abstract

A detailed biophysical model for a neuron/astrocyte network is developed to explore mechanisms responsible for the initiation and propagation of cortical spreading depolarizations and the role of astrocytes in maintaining ion homeostasis, thereby preventing these pathological waves. Simulations of the model illustrate how properties of spreading depolarizations, such as wave speed and duration of depolarization, depend on several factors, including the neuron and astrocyte Na+-K+ ATPase pump strengths. In particular, we consider the neuroprotective role of astrocyte gap junction coupling. The model demonstrates that a syncytium of electrically coupled astrocytes can maintain a physiological membrane potential in the presence of an elevated extracellular K+ concentration and efficiently distribute the excess K+ across the syncytium. This provides an effective neuroprotective mechanism for delaying or preventing the initiation of spreading depolarizations.