How does Spreading Depression Spread? - Physiology and Modeling

TL;DR

This review discusses mathematical models, including Hodgkin-Huxley and activator-inhibitor types, to understand the mechanisms and spatial spread of spreading depression in cortical tissue, highlighting recent advances in linking these models.

Contribution

It provides a comprehensive overview of modeling approaches for spreading depression, emphasizing the integration of different mathematical tools to study its mechanisms and extent.

Findings

Hodgkin-Huxley models elucidate ionic mechanisms of SD.

Activator-inhibitor models capture spatial dynamics of SD.

Recent techniques link different modeling frameworks.

Abstract

Spreading depression (SD) is a wave phenomenon in gray matter tissue. Locally, it is characterized by massive re-distribution of ions across cell membranes. As a consequence, there is a sustained membrane depolarization and tissue polarization that depresses any normal electrical activity. Despite these dramatic cortical 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.