Effects of Glia in a Triphasic Continuum Model of Cortical Spreading Depression

Cortical spreading depression (SD) is a spreading disruption in brain ionic homeostasis during which neurons experience complete and prolonged depolarizations. SD is generally believed to be the physiological substrate of migraine aura and is associated with many other brain pathologies. Here, we perform simulations with a model of SD treating brain tissue as a triphasic continuum of neurons, glia and the extracellular space. A thermodynamically consistent incorporation of the major biophysical effects, including ionic electrodiffusion and osmotic water flow, allows for the computation of important physiological variables including the extracellular voltage (DC) shift. A systematic parameter study reveals that glia can act as both a disperser and buffer of potassium in SD propagation. Furthermore, we show that the timing of the DC shift with respect to extracellular rise is highly dependent on glial parameters, a result with implications for the identification of the propagating mechanism of SD.