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脑内动态细胞外空间的时间分辨定量:皮质扩散性抑制研究。

Time-resolved quantification of the dynamic extracellular space in the brain: study of cortical spreading depression.

机构信息

Multidisciplinary Research Center, Shantou University , Shantou, Guangdong , China.

Neurosurgery Division, Second Affiliated Hospital of the School of Medicine, Shantou University , Shantou, Guangdong , China.

出版信息

J Neurophysiol. 2019 May 1;121(5):1735-1747. doi: 10.1152/jn.00348.2018. Epub 2019 Feb 20.

DOI:10.1152/jn.00348.2018
PMID:30786223
Abstract

Extracellular diffusion in the brain is customarily characterized by two parameters, the extracellular space (ECS) volume fraction α and the diffusion tortuosity λ. How these two parameters are temporarily modified and correlated in a physiological/pathological event remains unclear to date. Using tetramethylammonium (TMA) as an ECS ion tracer in a newly updated iontophoretic sinusoidal method, we studied in this work the dynamic α() and λ() in rat somatosensory cortex during spreading depression (SD). Temporal variations of α() and λ(), as evoked by SD, were obtained through analyses of the extracellular TMA diffusion waveform resulting from a sinusoidally modulated point source. Most of the time, cortical SD induced coordinated α() decreases and λ() increases. In rare occasions, SD induced sole decreases of α() with no changes in λ(). The independent modulation of α() and λ() was neither associated with cortical anatomy nor with the specific shape of the SD field potential wave. Changes of α() and λ() often took place acutely at the onset of SD, followed by a more transient modulation. Compared with the prior iontophoretic methods of TMA, the sinusoidal method provides time-resolved quantification of α() and λ() in relative terms but also raises a higher property requirement on the TMA-selective microelectrode. The sinusoidal method could become a valuable tool in the studies of the dynamic ECS response in various brain events. An iontophoretic sinusoidal method was applied to study the dynamic changes of two extracellular space parameters, the extracellular volume fraction α() and tortuosity λ(), in the brain during cortical spreading depression. Both parameters showed coordinated (most often) and independent (rarely) modulations in spreading depression. The sinusoidal method is equally applicable to other acute pathological events and a valuable tool to study the functional role of extracellular space in brain events.

摘要

细胞外扩散在大脑中通常由两个参数来描述,即细胞外空间(ECS)体积分数α和扩散迂曲度λ。这两个参数在生理/病理事件中是如何暂时改变和相互关联的,目前还不清楚。本研究使用四甲基铵(TMA)作为 ECS 离子示踪剂,在一种新的更新的离子电泳正弦波方法中,研究了在扩散性抑制(SD)期间大鼠体感皮层中α()和λ()的动态变化。通过分析由正弦调制点源产生的细胞外 TMA 扩散波形,得到了由 SD 诱发的α()和λ()的时变。大多数情况下,皮层 SD 诱导α()协同减少和λ()增加。在极少数情况下,SD 仅诱导α()的减少,而λ()没有变化。α()和λ()的独立调节既与皮层解剖结构无关,也与 SD 场电位波的特定形状无关。α()和λ()的变化通常在 SD 开始时急性发生,随后是更短暂的调节。与之前的 TMA 离子电泳方法相比,正弦波方法提供了相对α()和λ()的时间分辨定量,但对 TMA 选择性微电极提出了更高的性能要求。正弦波方法可能成为研究各种脑事件中动态 ECS 反应的有用工具。 一种离子电泳正弦波方法被应用于研究大脑皮层扩散性抑制期间两个细胞外空间参数,即细胞外体积分数α()和迂曲度λ()的动态变化。这两个参数在扩散性抑制中都表现出协同(大多数情况下)和独立(很少情况下)的调节。正弦波方法同样适用于其他急性病理事件,是研究脑事件中细胞外空间功能作用的有用工具。

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