Dynamics of Ionic Shifts in Cortical Spreading Depression.
Dynamics of Ionic Shifts in Cortical Spreading Depression.
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DOI：
10.1093/cercor/bhv054
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Nagelhus EA
中科院分区：
文献类型：
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作者：
Enger R;Tang W;Vindedal GF;Jensen V;Johannes Helm P;Sprengel R;Looger LL;Nagelhus EA
皮层扩散性抑制是脑细胞几乎完全去极化的缓慢传播波，随后是神经元活动的暂时抑制。越来越多的证据表明，皮层扩散性抑制是偏头痛先兆的基础，类似的波促进中风、创伤和出血中的组织损伤。皮质扩散性抑制的特征在于神经元肿胀、细胞外钾和谷氨酸的显著升高、多相血流变化和组织氧张力下降。皮层扩散性抑制波的缓慢速度意味着它是由一种化学物质的扩散介导的，但这种物质的身份和它所遵循的路径是未知的。已经提出了缝隙连接偶联神经元或神经胶质细胞之间的细胞间扩散和K+或谷氨酸的间质扩散。在这里，我们使用细胞外直流电位记录，K+敏感的微电极，和2-光子成像与超灵敏的Ca 2+和谷氨酸荧光探针，以阐明与传播的皮质扩散性抑制在成年小鼠的视觉皮层的离子位移的时空动态。我们的数据反对细胞间的Ca 2+扩散进行皮层扩散性抑制波阵面和有利于间质K+扩散，而不是谷氨酸扩散，作为皮层扩散性抑制的主导事件。
Cortical spreading depression is a slowly propagating wave of near-complete depolarization of brain cells followed by temporary suppression of neuronal activity. Accumulating evidence indicates that cortical spreading depression underlies the migraine aura and that similar waves promote tissue damage in stroke, trauma, and hemorrhage. Cortical spreading depression is characterized by neuronal swelling, profound elevation of extracellular potassium and glutamate, multiphasic blood flow changes, and drop in tissue oxygen tension. The slow speed of the cortical spreading depression wave implies that it is mediated by diffusion of a chemical substance, yet the identity of this substance and the pathway it follows are unknown. Intercellular spread between gap junction-coupled neurons or glial cells and interstitial diffusion of K+ or glutamate have been proposed. Here we use extracellular direct current potential recordings, K+-sensitive microelectrodes, and 2-photon imaging with ultrasensitive Ca2+ and glutamate fluorescent probes to elucidate the spatiotemporal dynamics of ionic shifts associated with the propagation of cortical spreading depression in the visual cortex of adult living mice. Our data argue against intercellular spread of Ca2+ carrying the cortical spreading depression wavefront and are in favor of interstitial K+ diffusion, rather than glutamate diffusion, as the leading event in cortical spreading depression.