Cortical spreading depression and migraine

Subjects

Abstract

Cortical spreading depression (CSD), a slowly propagated wave of depolarization followed by suppression of brain activity, is a remarkably complex event that involves dramatic changes in neural and vascular function. Since its original description in the 1940s, CSD has been hypothesized to be the underlying mechanism of the migraine aura. Substantial evidence from animal models provides indirect support for this hypothesis, and studies showing that CSD is common in humans with brain injury clearly demonstrate that the phenomenon can occur in the human brain. Considerable uncertainty about the role of CSD in migraine remains, however, and key questions about how this event is initiated, how it spreads, and how it might cause migraine symptoms remain unanswered. This Review summarizes current concepts of CSD and its potential roles in migraine, and addresses ongoing studies aimed at a clearer understanding of this fundamental brain phenomenon.

Key Points

  • Cortical spreading depression (CSD) is a slowly propagating wave of altered brain activity that involves dramatic changes in neuronal, glial and vascular function

  • CSD has recently been extensively characterized in humans via recordings from the exposed brain surface in patients with brain injury

  • The widely accepted hypothesis that CSD is the physiological mechanism underlying the migraine aura is supported by substantial evidence from animal models, but definitive proof in patients with migraine is lacking

  • Studies in animals indicate that CSD can activate pain pathways, but the role of CSD as a potential trigger for migraine headache remains uncertain

  • CSD is a fundamental pattern of brain signalling that provides an opportunity for greater understanding of nervous system physiology, and for the identification of new therapies for migraine and other brain disorders

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Figure 1: CSD studied by electrophysiological recording and optical imaging in the mouse.
Figure 2: Cortical spreading depression: risk factors, triggers, mechanisms and functional consequences.

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Both authors researched data for the article, discussed the content, wrote the text, and reviewed and edited the manuscript before submission.

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Charles, A., Baca, S. Cortical spreading depression and migraine. Nat Rev Neurol 9, 637–644 (2013). https://doi.org/10.1038/nrneurol.2013.192

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