How does spreading depression spread? Physiology and modeling

Abstract

<jats:title>Abstract</jats:title><jats:p>Spreading depression (SD) is a wave phenomenon in gray matter tissue. Locally, it is characterized by massive redistribution of ions across cell membranes. As a consequence, there is sustained membrane depolarization and tissue polarization that depress any normal electrical activity. Despite these dramatic events, SD remains difficult to observe in humans noninvasively, which, for long, has slowed advances in this field. The growing appreciation of its clinical importance in migraine and stroke is therefore consistent with an increasing need for computational methods that tackle the complexity of the problem at multiple levels. In this review, we focus on mathematical tools to investigate the question of spread and its two complementary aspects: What are the physiological mechanisms and what is the spatial extent of SD in the cortex? This review discusses two types of models used to study these two questions, namely, Hodgkin-Huxley type and generic activator-inhibitor models, and the recent advances in techniques to link them.</jats:p>

Holes in the leaky migraine blood–brain barrier hypothesis?

“…Contralateral headache would be an expectation if thalamus and cortex on the same side as the CSD were processing transmitted pain signals. CSDs that are less intense or that are limited in spatial distribution (Zandt et al, 2015), and/or reflect more efficient tissue clearance of nociceptive molecules may explain why some people with migraine do not experience headache after aura. Consistent with the above formulation, trigeminal axons and cell bodies are known to express multiple 5-HT1 receptor subtypes plus CGRP and its cognate receptor, which figure prominently as therapeutic targets (see below).…”

A computational multiscale model of cortical spreading depression propagation

“…[7]). Four hypothesis to explain the CSD propagation on the cortex have been proposed, and the two most accepted ones suggest that CSD propagates due to diffusion of potassium or glutamate in the extracellular space, which is presumed to follow ordinary diffusion laws [8]. Differently from what happens in modeling cardiac electrophysiology (see, among others, [27,28] for an overview of the topic), setting up a distributed model for the membrane potential would not be effective in the description of CSD.…”

“…[7]). CSD is characterised by relevant increases in both extracellular K + and glutamate, as well as rises in intracellular Na + and Ca 2+ , and the two most accepted hypotheses suggest that its propagation is due to diffusion of potassium or glutamate in the extracellular space [8].…”

“…For a general overview of those models we refer the reader to [8,12,13,14]. Recently, an increasing attention has been paid to the effects of the cortical geometry on CSD propagation, as fissures and sulci of the cortex are expected to influence the propagation of depolarization waves.…”

Hot spots and labyrinths: Why neuromodulation devices for episodic migraine should be personalized

“…In this study, we used a generic model with generic rate functions. The model and its physiological interpretation can be found in a detailed review by Zandt et al (2015) [available on request]. Briefly, the model is of activator-inhibitor type.…”