Migraine-Headache Institute, Gupta Medical Center, S-407, Greater Kailash-II, New Delhi, 110 048, India.
Expert Rev Neurother. 2009 Nov;9(11):1595-614. doi: 10.1586/ern.09.103.
Cortical spreading depression (CSD) has been at the center stage of migraine pathophysiology for approximately six decades. Reanalysis of CSD reveals several major unbridgeable gaps in this experimental neurophysiologic concept for migraine. Key phenotypic and pharmacological features of migraine challenge the assumed pathophysiologic role of CSD. Detection of subclinical infarct-like white matter lesions (WMLs) in the brain of some migraine patients stimulated the concept of CSD-related BBB disruption. Raised plasma levels of matrix metalloproteinases (MMPs) in migraine patients in the headache phase, specifically MMP-9, suggested a pathogenetic role for MMP elevation in the development of both migraine attacks and WMLs. Migraine attacks with or without aura present a unique, profound and protracted vasodilatory challenge to the homeostatic systems of the brain. To accommodate the rather sudden increase in cerebral blood flow, the brain circulatory network must dilate and the BBB must expand considerably. MMPs can influence expansion of the extracellular matrix of the BBB and loosening of the intercellular tight junctions between endothelial cells through proteolytic degradation during migrainous cerebrovascular dilatation. WMLs most probably reflect transient and discrete breakdown of the BBB consequent to sustained cerebral hyperperfusion rather than hypoperfusion. Systemic elevations of MMPs are not specific to migraine but are found in a variety of neurological and extra-neurological disorders. This perspective presents a conceptual dissociation between the effects of CSD on the brain of experimental animals and the clinical phenomena in migraine patients.
皮层扩散性抑制（CSD）作为偏头痛病理生理学的核心概念已近 60 年。对 CSD 的重新分析揭示了这个用于解释偏头痛的实验神经生理学概念中几个重大的无法弥合的差距。偏头痛的关键表型和药理学特征对 CSD 的假定病理生理学作用提出了挑战。在一些偏头痛患者的大脑中检测到亚临床梗死样的白质病变（WML），这刺激了与 CSD 相关的 BBB 破坏的概念。偏头痛患者头痛期血浆中基质金属蛋白酶（MMPs）水平升高，特别是 MMP-9，表明 MMP 升高在偏头痛发作和 WML 发展中具有发病作用。有或无先兆的偏头痛发作对大脑的稳态系统构成了独特、深刻和持久的血管扩张挑战。为了适应脑血流的突然增加，脑循环网络必须扩张，BBB 必须大大扩张。MMPs 可以通过偏头痛性脑血管扩张期间的蛋白水解降解，影响 BBB 细胞外基质的扩张和内皮细胞之间细胞间紧密连接的松动。WML 最有可能反映出持续的脑过度灌注导致的 BBB 短暂和离散的破坏，而不是灌注不足。MMPs 的全身升高不仅限于偏头痛，而且在各种神经和非神经疾病中都有发现。这种观点提出了 CSD 对实验动物大脑的影响与偏头痛患者的临床现象之间的概念分离。
