Fig. 2

CSD-induced inflammatory activity propagates through the brain, meninges, and skull. A. PET studies utilizing inflammation markers revealed bi-hemispheric cortical as well as subcortical inflammatory tracer uptake in patients suffering from frequent migraine with aura attacks. B. Consistent with clinical observations, Panx1 activity, monitored by propidium iodide (PI) influx to neurons (red fluorescence), was not confined to the cortex (Cx) ipsilateral to CSD but was also evident in the contralateral cortex and subcortical structures such as the dentate gyrus (DG) in the mouse brain. C. Simultaneous tracer uptake ([¹¹C]PBR28) was observed in the affected occipital cortex responsible for generating the aura and the overlying dura, extending to the adjacent bone marrow. These findings suggest that myeloid cells may also contribute to inflammation in addition to the inflammatory mediators released from astrocyte endfeet and dural cells (D), thus underscoring the significance of sustained dural inflammation in migraine headache generation. Lym: lymphocyte, DC: dendritic cell, Mac: macrophage, Mono: monocyte, MC: mast cell. Reproduced from [10, 19, 91] with permission. Illustrations were created using BioRender.com and Servier Medical Art (http://www.servier.com).