Cortical spreading depression as a target for anti-migraine agents.
Cortical spreading depression as a target for anti-migraine agents.
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DOI：
10.1186/1129-2377-14-62
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发表时间：
2013-07-23
期刊：
影响因子：
--
通讯作者：
Sarchielli P
中科院分区：
文献类型：
--
作者：
Costa C;Tozzi A;Rainero I;Cupini LM;Calabresi P;Ayata C;Sarchielli P
扩散性抑制（SD）是持续几分钟的神经元和胶质细胞去极化的缓慢传播波，其可以在电、机械或化学去极化刺激后在大脑皮层或其他脑区域内发展。皮质SD（CSD）被认为是偏头痛先兆的神经生理学相关因素。其特征在于细胞外K+和谷氨酸的大量增加，以及细胞内Na+和Ca2+的升高。这些离子位移产生可以在细胞外记录的缓慢直流（DC）电位位移。此外，CSD与皮质实质血流的变化有关。CSD已被证明是目前处方的偏头痛预防药物的常见治疗靶点。然而，没有观察到抗癫痫药物卡马西平和奥卡西平的效果，这与它们对偏头痛缺乏疗效一致。已经测试了一些对偏头痛感兴趣的分子对CSD的影响。具体而言，阻断CSD可能对新型苯并吡喃衍生物托那博沙在预防有先兆的偏头痛中发挥促进作用。此外，降钙素基因相关肽（CGRP）拮抗剂最近已报道抑制CSD，表明CGRP受体激活的CSD的启动和维持不仅在经典的血管网站，而且在中枢神经元水平的贡献。了解这一贡献背后的可能原因，将进一步深入了解“gepants”的作用机制，这可能是这些药物作为抗偏头痛药物的有效性的关键。CSD模型是测试当前和新型预防药物的有用工具，提供了与偏头痛相关的作用机制的知识。
Spreading depression (SD) is a slowly propagating wave of neuronal and glial depolarization lasting a few minutes, that can develop within the cerebral cortex or other brain areas after electrical, mechanical or chemical depolarizing stimulations. Cortical SD (CSD) is considered the neurophysiological correlate of migraine aura. It is characterized by massive increases in both extracellular K+ and glutamate, as well as rises in intracellular Na+ and Ca2+. These ionic shifts produce slow direct current (DC) potential shifts that can be recorded extracellularly. Moreover, CSD is associated with changes in cortical parenchymal blood flow. CSD has been shown to be a common therapeutic target for currently prescribed migraine prophylactic drugs. Yet, no effects have been observed for the antiepileptic drugs carbamazepine and oxcarbazepine, consistent with their lack of efficacy on migraine. Some molecules of interest for migraine have been tested for their effect on CSD. Specifically, blocking CSD may play an enabling role for novel benzopyran derivative tonabersat in preventing migraine with aura. Additionally, calcitonin gene-related peptide (CGRP) antagonists have been recently reported to inhibit CSD, suggesting the contribution of CGRP receptor activation to the initiation and maintenance of CSD not only at the classic vascular sites, but also at a central neuronal level. Understanding what may be lying behind this contribution, would add further insights into the mechanisms of actions for “gepants”, which may be pivotal for the effectiveness of these drugs as anti-migraine agents. CSD models are useful tools for testing current and novel prophylactic drugs, providing knowledge on mechanisms of action relevant for migraine.
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