Mechanically-induced cortical spreading depression associated regional cerebral blood flow changes are blocked by Na+ ion channel blockade
Mechanically-induced cortical spreading depression associated regional cerebral blood flow changes are blocked by Na+ ion channel blockade
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DOI：
10.1016/j.brainres.2008.07.014
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发表时间：
2008-09-10
期刊：
影响因子：
2.9
通讯作者：
Goadsby, Peter J.
中科院分区：
文献类型：
--
作者：
Akerman, Simon;Holland, Philip R.;Goadsby, Peter J.
有先兆的偏头痛发生在所有偏头痛患者的20-30%。皮质扩散性抑制（CSD）过程中局部脑血流量（rCBF）的变化被认为是先兆的实验相关性。CSD与脑离子稳态的失败和兴奋性氨基酸从神经细胞的流出同步。因此，研究CSD的机制，如离子通道的操纵，并观察rCBF的变化可能有助于我们了解偏头痛先兆。在这项研究中，我们使用机械刺激，以诱导少血和充血，在手术准备的猫和大鼠，使用激光多普勒探针来测量脑血流量和单细胞皮层记录来测量尖峰/神经元爆发，两者都产生的CSD的结果。我们研究了针对钠离子通道、电压依赖性钙离子通道和ATP激活的钾离子通道的离子通道阻滞剂的反应。钠离子通道阻滞剂能够抑制猫和大鼠的YCBF变化。电压依赖性钙通道阻滞剂对扩散的起始或传播几乎没有影响，ATP激活的钾通道阻滞剂也是如此。这些数据与已知的人类先兆钠离子通道主要参与机械刺激诱导的YCBF变化一致，因此可能代表偏头痛先兆反应的治疗靶点。(C)2008 Elsevier B. V.保留所有权利。
Migraine with aura occurs in up to 20-30% of all migraineurs. The regional cerebral blood flow (rCBF) changes that occur during cortical spreading depression (CSD) are considered to be an experimental correlate of aura. CSD is synchronous with a failure in brain ion homeostasis and efflux of excitatory amino acids from nerve cells. Therefore studying the mechanisms that underlie CSD, such as ion channel manipulation, and observing rCBF changes may help our understanding of migraine aura. In this study we used mechanical stimulation to induce oligemia and hyperemia, in surgically prepared cats and rats, using laser Doppler probes to measure the cerebral blood flow and single cell cortical recording to measure the spike/ neuronal burst, both generated as a consequence of CSD. We looked at the response of ion channel blockers directed at sodium, voltage-dependent calcium and ATP-activated potassium ion channels. The sodium ion channel blocker was able to inhibit YCBF changes in both the cat and rats. Voltage -dependent calcium channel blockers had little effect on the initiation or propagation of the spread, as did the ATP-activated potassium channel blocker. The data are consistent with what is known of human aura in that sodium ion channels are those predominantly involved in mechanical stimulation-induced YCBF changes and thus may represent therapeutic targets for the aura response in migraine. (C) 2008 Elsevier B.V. All rights reserved.