Figure 5.

Microglial activation is influenced by the number of CSD episodes. A single CSD event, as seen in the usual aura of migraine patients, does not cause significant release of HMGB1 from cortical neurons. Conversely, clustering of CSD, as seen in stroke and brain trauma, induces a robust HMGB1 release from cortical neurons. Subsequently, HMGB1 acts on the TLR2/4 on the surface of microglia, which is followed by microglial activation, as demonstrated by their hypertrophic morphological alterations. The functional significance of microglial activation in this setting remains uncertain. They may contribute to neuroprotection, for example, through the synaptic repair on the dendritic spines of multiple CSD-affected cortical neurons. Alternatively, activated microglia may exert injurious actions.