Spreading depolarization triggers pro- and anti-inflammatory signalling: a potential link to headache

作者：Ζeynep Kaya, Nevin Belder, Melike Sever, Şefik Evren Erdener, Buket Dönmez‐Demir, Canan Bağcı, Merve Nur Köroğlu, Kaya Bilgüvar, Turgay Dalkara · 发表于：Brain · 年份：2025 · DOI：10.1093/brain/awaf015 · 被引用次数：23 · 研究领域：Migraine and Headache Studies、Circadian rhythm and melatonin、Sleep and Wakefulness Research

Cortical spreading depolarization (CSD), the neurophysiological event believed to underlie aura, might trigger migraine headaches through inflammatory signalling that originates in neurons and spreads to the meninges via astrocytes. Increasing evidence from studies on rodents and migraine patients supports this hypothesis. The transition from pro-inflammatory to anti-inflammatory mechanisms is crucial for resolving inflammation. However, the resolution of inflammation in the context of CSD and migraine headaches remains poorly understood. This study aims to elucidate the progression of post-CSD inflammatory signalling and its resolution in neurons, astrocytes and microglia in mouse brains. CSD was triggered optogenetically or by pinprick. High mobility group box 1 release, caspase-1 activation and cell-specific activation of nuclear factor kappa B (NF-κB) pairs, along with ensuing transcriptomic changes, were evaluated using immunofluorescence, western blotting, co-immunoprecipitation, fluorescence resonance energy transfer analysis and cell-specific transcriptomics. Our findings indicate that after the initial burst, high mobility group box 1 release from neurons ceased, and caspase-1 activation, which peaked 1 h post-CSD, diminished within 3-5 h. This suggests that pro-inflammatory stimuli driving inflammatory signalling decreased within hours after CSD. Pro-inflammatory NF-κB p65:p50 pairs, along with anti-inflammatory cRel:p65 pairs, were detected in astrocyte nuclei shor...