Fig. 2

Possible pathogenetic mechanisms of migraine involving the glymphatic system dysfunction. CSD can be responsible for a transient PVS closure causing a GS impairment. The GS dysfunction can lead to the accumulation of excitatory, pro-inflammatory and vasodilator molecules involved in the development and the exacerbation of migraine. CSD: cortical spreading depression; PVS: perivascular space; ROS: reactive oxygen species; CGRP: calcitonin gene-related peptide; ATP: adenosine triphosphate; TNF-α: tumor necrosis factor alpha; IL-1β: interleukin 1-beta; HIF-1α: hypoxia-inducible factor 1-alpha