Fig. 1

Proposed mechanism on how migraine might facilitate the onset of MS. During a migraine attack, SD causes leakage of the blood–brain-barrier (BBB) (indicated by black dotted lines between endothelial cells) through release of matrix metalloproteinases (MMP-9; purple dots). Peripheral white blood cells (WBC; green) traffic across the permeable BBB. Infiltrated immune cells may get exposed and sensitized to myelin proteins (red dots), via antigen-presenting cells (APC) or through direct exposure from oligodendrocytes (OD). Previously sensitized autoreactive WBC (auto-WBC; light green) may re-enter the CNS from the peripheral circulation during migraine attack-triggered BBB breakdown and release inflammatory mediators (purple dots) with the help of microglia (purple cell), resulting in demyelination and axonal loss.