Department of Molecular Neurobiology, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Butlerova Street 5A, 117485, Moscow, Russia.
Pirogov Russian National Research Medical University, Ostrovityanova Street 1, 117997, Moscow, Russia.
J Headache Pain. 2024 Jul 16;25(1):113. doi: 10.1186/s10194-024-01823-1.
Neurogenic meningeal inflammation is regarded as a key driver of migraine headache. Multiple evidence show importance of inflammatory processes in the dura mater for pain generation but contribution of the leptomeninges is less clear. We assessed effects of cortical spreading depolarization (CSD), the pathophysiological mechanism of migraine aura, on expression of inflammatory mediators in the leptomeninges.
A single CSD event was produced by a focal unilateral microdamage of the cortex in freely behaving rats. Three hours later intact cortical leptomeninges and parenchyma of ipsi-lesional (invaded by CSD) and sham-treated contra-lesional (unaffected by CSD) hemispheres were collected and mRNA levels of genes associated with inflammation (Il1b, Tnf, Ccl2; Cx3cl1, Zc3h12a) and endocannabinoid CB2 receptors (Cnr2) were measured using qPCR.
Three hours after a single unilateral CSD, most inflammatory factors changed their expression levels in the leptomeninges, mainly on the side of CSD. The meninges overlying affected cortex increased mRNA expression of all proinflammatory cytokines (Il1b, Tnf, Ccl2) and anti-inflammatory factors Zc3h12a and Cx3cl1. Upregulation of proinflammatory cytokines was found in both meninges and parenchyma while anti-inflammatory markers increased only meningeal expression.
A single CSD is sufficient to produce pronounced leptomeningeal inflammation that lasts for at least three hours and involves mostly meninges overlying the cortex affected by CSD. The prolonged post-CSD inflammation of the leptomeninges can contribute to mechanisms of headache generation following aura phase of migraine attack.
神经源性脑膜炎症被认为是偏头痛头痛的关键驱动因素。多项证据表明硬脑膜中的炎症过程对疼痛产生很重要，但软脑膜的贡献尚不清楚。我们评估了皮质扩散性抑制（CSD），偏头痛先兆的病理生理机制，对软脑膜中炎症介质表达的影响。
在自由活动的大鼠中，通过皮质的单侧微损伤产生单个 CSD 事件。 3 小时后，采集同侧损伤（CSD 侵袭）和假处理对侧（不受 CSD 影响）半球完整皮质软脑膜和实质的 mRNA 水平，并测量与炎症相关的基因（Il1b、Tnf、Ccl2；Cx3cl1、Zc3h12a）和内源性大麻素 CB2 受体（Cnr2）的表达。使用 qPCR。
在单侧 CSD 后 3 小时，大多数炎症因子在软脑膜中的表达水平发生变化，主要是在 CSD 的一侧。受影响皮质上方的脑膜增加了所有促炎细胞因子（Il1b、Tnf、Ccl2）和抗炎因子 Zc3h12a 和 Cx3cl1 的 mRNA 表达。促炎细胞因子在上皮和脑膜中均上调，而抗炎标志物仅增加脑膜表达。
单次 CSD 足以产生明显的软脑膜炎症，至少持续 3 小时，并且主要涉及受 CSD 影响的皮质上方的脑膜。CSD 后软脑膜的长期炎症可能有助于偏头痛攻击先兆期后头痛产生的机制。
