Role of cortical spreading depression in the pathophysiology of migraine

Abstract

A migraine is a recurring neurological disorder characterized by unilateral, intense, and pulsatile headaches. In one-third of migraine patients, the attacks are preceded by a visual aura, such as a slowly-propagating scintillating scotoma. Migraine aura is thought to be a result of the neurovascular phenomenon of cortical spreading depression (SD), a self-propagating wave of depolarization that spreads across the cerebral cortex. Several animal experiments have demonstrated that cortical SD causes intracranial neurogenic infl ammation around the meningeal blood vessels, such as plasma protein extravasation and pro-inflammatory peptide release. Cortical SD has also been reported to activate both peripheral and central trigeminal nociceptive pathways. Although several issues remain to be resolved, recent evidence suggests that cortical SD could be the initial trigger of intracranial neurogenic inflammation, which then contributes to migraine headaches via subsequent activation of trigeminal afferents.Keywords: cortical spreading depression; migraine; neurogenic inflammation; PET; trigeminal nociceptive pathway ·Review· IntroductionCortical spreading depression (SD), described first by Leao [1] , is a self-propagating wave of transient neuronal/ glial membrane depolarization that is accompanied by a transient negative shift of the direct current (DC) potential [2] and temporal elevation of cerebral blood flow (CBF) [3,4] throughout the cerebral hemisphere at a rate of 2-5 mm/ min [1, 5,6] . The rate of spreading correlates with the observed spread of the aura of a classical migraine [7] , which is characterized by a spot of fl ickering light that appears near the center of the visual field and then gradually expands outward [8][9][10] . Recently, cortical SD has been hypothesized to be the initial event involved in migraine headaches.Moskowitz et al. [11,12] proposed that pro-inflammatory peptides, such as substance P and calcitonin generelated peptide (CGRP), released from trigeminocervical nerve terminals in response to some unknown stimulation, probably cortical SD, induces vasodilation and plasma protein extravasation. Such neurogenic inflammation is thought to trigger a headache via stimulation of trigeminal afferents. Consistent with this hypothesis, cortical SD induced intracranial neurogenic inflammation around the meningeal blood vessels [13][14][15] , and subsequent activation of both peripheral [16] and central [17] trigeminal nociceptive pathways has been described. Here, we review the experimental evidence mainly from neurophysiological studies that has advanced the understanding of whether and how the neurovascular phenomenon of cortical SD causes intracranial neurogenic inflammation, and subsequently participates in triggering a migraine headache. Migraine PathophysiologyA migraine is a recurring neurological disorder characterized Yilong Cui, et al . Role of cortical spreading depression in the pathophysiology of migraine 813 by unilateral, intense, and pulsatile headaches lasting 4-72 h [18] , a...

Magnetic resonance imaging arterial‐spin‐labelling perfusion alterations in childhood migraine with atypical aura: a case–control study

“…Of note, the duration of hypoperfusion (up to 14h) also appeared to be strikingly long as compared with previous literature, also accounting for the specificity of these atypical events. While the pathophysiology of these events is not fully understood, and likely differs by subtype, recent works are paving the way towards a better understanding of the mechanisms involved …”

BF-1 – A novel selective 5-HT2B receptor antagonist blocking neurogenic dural plasma protein extravasation in guinea pigs

“…Recent studies indicate that the brain serotonergic system contributes to the propagation of CSD (reviewed by Cui et al, 2014). We have not considered this model in our study since a) in this model the serotonin contribution seems to be mediated by 5-HT 1A , 5-HT 2A , and 5-HT 3 receptors (reviewed by Cui et al, 2014), b) the reduction of CSD by methysergide was not statistically significant (Ayata et al, 2006), and c) 5-HT 2B receptors are not expressed in the human brain .…”

Transcriptomic Changes in Rat Cortex and Brainstem After Cortical Spreading Depression With or Without Pretreatment With Migraine Prophylactic Drugs

“…CSD is a neuronal phenomenon consisting of a short-lasting slow depolarization wave usually originated in the occipital cortex that moves forwards, and involves changes at different levels, such as the neuronal, glial and vascular systems. It is followed by a suppression of neuronal activity and local changes in the cerebral blood flow, and it has also been described in patients with stroke or brain injury 7,8 . It has been proposed that CSD might be able to activate the trigeminovascular system, innervating the meningeal blood vessels, and this activation is thought to be one of the mechanisms that underlie migraine pain 13,20 .…”