Pietrobon Daniela, Brennan K C
Department of Biomedical Sciences and Padova Neuroscience Center, University of Padova, Via Ugo Bassi 58, 35131, Padua, Italy.
Department of Neurology, University of Utah, 383 Colorow Drive, Salt Lake City, UT, 84108, USA.
J Headache Pain. 2025 Jan 27;26(1):17. doi: 10.1186/s10194-025-01948-x.
A key unanswered question in migraine neurobiology concerns the mechanisms that make the brain of migraineurs susceptible to cortical spreading depression (CSD, a spreading depolarization that underlies migraine aura and may trigger the migraine pain mechanisms). Important insights into this question can be obtained by studying the mechanisms of facilitation of CSD initiation in genetic mouse models of the disease. These models, all generated from families with hereditary migraine, allow the investigation of the functional consequences of disease-causing mutations at the molecular, cellular, synaptic and neural circuit levels. In this review, after describing the available genetic mouse models of migraine, which all share increased susceptibility to experimentally induced CSD, we will discuss the functional alterations in their cerebral cortex and the mechanisms underlying the facilitation of CSD initiation in their cortex, as well as the insights that these mechanisms may give into the mechanisms of initiation of spontaneous CSDs in migraine.
偏头痛神经生物学中一个关键的未解决问题涉及使偏头痛患者大脑易患皮层扩散性抑制（CSD，一种作为偏头痛先兆基础的扩散性去极化，可能触发偏头痛疼痛机制）的机制。通过研究该疾病的基因小鼠模型中CSD起始促进机制，可以获得对这个问题的重要见解。这些模型均来自患有遗传性偏头痛的家族，能够在分子、细胞、突触和神经回路水平上研究致病突变的功能后果。在这篇综述中，在描述了现有的偏头痛基因小鼠模型（所有这些模型对实验诱导的CSD敏感性均增加）之后，我们将讨论它们大脑皮层中的功能改变以及其皮层中CSD起始促进的潜在机制，以及这些机制可能为偏头痛中自发性CSD起始机制提供的见解。
