Investigating paradoxical hysteresis effects in the mouse neocortical slice model
Investigating paradoxical hysteresis effects in the mouse neocortical slice model
复制标题
DOI：
10.1016/j.ejphar.2011.11.045
复制
发表时间：
2012-01-30
影响因子：
5
通讯作者：
Sleigh, James W.
中科院分区：
文献类型：
--
作者：
Voss, Logan J.;Brock, Magdalena;Sleigh, James W.
临床上，麻醉药物在诱导时与从麻醉诱导的意识丧失中苏醒时的血浆药物浓度显示滞后。这被认为是血浆和脑效应部位之间的药代动力学滞后的结果，反之亦然。然而，最近的数学和实验研究表明，麻醉滞后可能是由于部分滞后的大脑生理，独立于药物转运延迟所谓的“神经惯性”。本研究的目的是探讨神经惯性在减少新皮层小鼠切片模型。通过将皮质切片暴露于无镁人工脑脊液（aCSF）来产生癫痫样事件（SLE）活动。通过操纵SLE频率、使用全身麻醉药依托咪酯和改变aCSF镁浓度来产生浓度效应环。依托咪酯（24 μ M）浓度-效应关系显示出明显的滞后，与依托咪酯缓慢扩散到切片组织中一致。操纵组织兴奋性，使用卡巴胆碱（50 μ M）或钾升高（5毫米与2.5毫米）没有显着改变依托咪酯滞后回线的大小。镁浓度-效应关系中的滞后是明显的，但仅当起始条件是含镁的“正常”aCSF时。离体大脑皮层切片表现出通路依赖性的“神经惯性”，可能是研究大脑皮层神经惯性机制的一个有价值的模型。(C)出版社：Elsevier B. V.
Clinically, anesthetic drugs show hysteresis in the plasma drug concentrations at induction versus emergence from anesthesia induced unconsciousness. This is assumed to be the result of pharmacokinetic lag between the plasma and brain effect-site and vice versa. However, recent mathematical and experimental studies demonstrate that anesthetic hysteresis might be due in part to lag in the brain physiology, independent of drug transport delay-so-called "neural inertia". The aim of this study was to investigate neural inertia in the reduced neocortical mouse slice model. Seizure-like event (SLE) activity was generated by exposing cortical slices to no-magnesium artificial cerebrospinal fluid (aCSF). Concentration-effect loops were generated by manipulating SLE frequency, using the general anesthetic drug etomidate and by altering the aCSF magnesium concentration. The etomidate (24 mu M) concentration-effect relationship showed a clear hysteresis, consistent with the slow diffusion of etomidate into slice tissue. Manipulation of tissue excitability, using either carbachol (50 mu M) or elevated potassium (5 mM vs 2.5 mM) did not significantly alter the size of etomidate hysteresis loops. Hysteresis in the magnesium concentration-effect relationship was evident, but only when the starting condition was magnesium-containing "normal" aCSF. The in vitro cortical slice manifests pathway-dependent "neural inertia" and may be a valuable model for future investigations into the mechanisms of neural inertia in the cerebral cortex. (C) 2011 Published by Elsevier B.V.