Enger Rune, Tang Wannan, Vindedal Gry Fluge, Jensen Vidar, Johannes Helm P, Sprengel Rolf, Looger Loren L, Nagelhus Erlend A
Department of Neurology, Oslo University Hospital, 0027 Oslo, Norway Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway Department of Molecular Medicine, Letten Centre and GliaLab, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, 0318 Oslo, Norway Department of Molecular Medicine, Letten Centre and GliaLab, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway Department of Molecular Neurobiology, Max Planck Institute for Medical Research, D69120 Heidelberg, Germany.
Cereb Cortex. 2015 Nov;25(11):4469-76. doi: 10.1093/cercor/bhv054. Epub 2015 Apr 2.
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 Ca(2+) 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 Ca(2+) 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.
皮层扩散性抑制是一种缓慢传播的近乎完全去极化的脑细胞波，随后神经元活动暂时受到抑制。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，并且类似的波在中风、创伤和出血中会促进组织损伤。皮层扩散性抑制的特征包括神经元肿胀、细胞外钾离子和谷氨酸水平显著升高、多相血流变化以及组织氧张力下降。皮层扩散性抑制波的缓慢传播速度表明它是由一种化学物质的扩散介导的，然而这种物质的身份及其传播途径尚不清楚。有人提出它是通过缝隙连接耦合的神经元或胶质细胞之间的细胞间传播以及钾离子或谷氨酸的间质扩散来实现的。在这里，我们使用细胞外直流电位记录、钾离子敏感微电极以及使用超灵敏钙离子和谷氨酸荧光探针的双光子成像技术，来阐明成年活体小鼠视觉皮层中与皮层扩散性抑制传播相关的离子变化的时空动态。我们的数据反对携带皮层扩散性抑制波前的钙离子的细胞间传播，并且支持间质钾离子扩散而非谷氨酸扩散是皮层扩散性抑制中的主要事件。
