Minimum conditions for the induction of cortical spreading depression in brain slices.
Minimum conditions for the induction of cortical spreading depression in brain slices.
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DOI：
10.1152/jn.00205.2014
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发表时间：
2014-11
影响因子：
2.5
通讯作者：
Yujie Tang;J. M. Méndez;J. Theriot;Punam M. Sawant;H. López-Valdés;Y. S. Ju;K. Brennan
中科院分区：
文献类型：
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作者：
Yujie Tang;J. M. Méndez;J. Theriot;Punam M. Sawant;H. López-Valdés;Y. S. Ju;K. Brennan
皮质扩散性抑制（CSD）发生在各种形式的脑损伤，如中风，蛛网膜下腔出血和脑外伤，但它也被认为是偏头痛先兆的机制。因此，预期在包括清醒行为状态的条件范围内发生。然而，在相对温和的条件下，如此大规模的去极化是如何发生的，目前还不清楚。在小鼠脑切片模型中使用具有局部刺激能力的微流体装置，我们改变细胞外钾浓度以及暴露于增加的细胞外钾的区域，以确定引发CSD所需的最低条件。重要的是，我们关注的是生理上合理的钾水平（≤145 mM;细胞内钾浓度）。我们发现阈值浓度和暴露于增加的细胞外钾的切片面积之间有很强的相关性：最小的暴露面积需要最高的钾浓度，而更大的面积需要在较低的浓度。我们还发现，适度升高的细胞外钾能够引起CSD在相对较小的估计组织体积，可能会被激活的非损伤条件下。因此，我们的研究结果表明，CSD可能是可诱导的条件下，预期在偏头痛先兆以及那些相关的脑外伤。
Cortical spreading depression (CSD) occurs during various forms of brain injury such as stroke, subarachnoid hemorrhage, and brain trauma, but it is also thought to be the mechanism of the migraine aura. It is therefore expected to occur over a range of conditions including the awake behaving state. Yet it is unclear how such a massive depolarization could occur under relatively benign conditions. Using a microfluidic device with focal stimulation capability in a mouse brain slice model, we varied extracellular potassium concentration as well as the area exposed to increased extracellular potassium to determine the minimum conditions necessary to elicit CSD. Importantly, we focused on potassium levels that are physiologically plausible (≤145 mM; the intracellular potassium concentration). We found a strong correlation between the threshold concentration and the slice area exposed to increased extracellular potassium: minimum area of exposure was needed with the highest potassium concentration, while larger areas were needed at lower concentrations. We also found that moderate elevations of extracellular potassium were able to elicit CSD in relatively small estimated tissue volumes that might be activated under noninjury conditions. Our results thus show that CSD may be inducible under the conditions that expected in migraine aura as well as those related to brain trauma.