Kudo Chiho, Nozari Ala, Moskowitz Michael A, Ayata Cenk
Department of Radiology, Stroke and Neurovascular Regulation Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Exp Neurol. 2008 Jul;212(1):201-6. doi: 10.1016/j.expneurol.2008.03.026. Epub 2008 Apr 11.
Cortical spreading depression (CSD), a transient neuronal and glial depolarization that propagates slowly across the cerebral cortex, is the putative electrophysiological event underlying migraine aura. It negatively impacts tissue injury during stroke, cerebral contusion and intracranial hemorrhage. Susceptibility to CSD has been assessed in several experimental animal models in vivo, such as after topical KCl application or cathodal stimulation. Various combinations of anesthetics and ambient conditions have been used by different laboratories making comparisons problematic and differences in data difficult to reconcile. We systematically studied CSD susceptibility comparing commonly used experimental anesthetics (isoflurane, alpha-chloralose, and urethane) with or without N(2)O or normobaric hyperoxia (100% O(2) inhalation). The frequency of evoked CSDs, and their propagation speed, duration, and amplitude were recorded during 2 h topical KCl (1 M) application. We found that N(2)O reduced CSD frequency when combined with isoflurane or urethane, but not alpha-chloralose; N(2)O also decreased CSD propagation speed and duration. Urethane anesthesia was associated with the highest CSD frequency that was comparable to pentobarbital. Inhalation of 100% O(2) did not alter CSD frequency, propagation speed or duration in combination with any of the anesthetics tested. Our data show anesthetic modulation of CSD susceptibility in an experimental model of human disease, underscoring the importance of proper study design for hypothesis testing as well as for comparing results between studies.
皮层扩散性抑制（CSD）是一种短暂的神经元和胶质细胞去极化现象，它在大脑皮层中缓慢传播，被认为是偏头痛先兆潜在的电生理事件。它对中风、脑挫伤和颅内出血期间的组织损伤有负面影响。在几种体内实验动物模型中评估了对CSD的易感性，例如局部应用氯化钾或阴极刺激后。不同实验室使用了各种麻醉剂和环境条件的组合，这使得比较存在问题，数据差异难以协调。我们系统地研究了CSD易感性，比较了常用的实验麻醉剂（异氟烷、α-氯醛糖和乌拉坦），有无一氧化二氮或常压高氧（吸入100%氧气）。在局部应用1 M氯化钾2小时期间，记录诱发CSD的频率及其传播速度、持续时间和幅度。我们发现，一氧化二氮与异氟烷或乌拉坦联合使用时可降低CSD频率，但与α-氯醛糖联合使用时则不然；一氧化二氮还降低了CSD的传播速度和持续时间。乌拉坦麻醉与最高的CSD频率相关，与戊巴比妥相当。与任何测试的麻醉剂联合使用时，吸入100%氧气均未改变CSD频率、传播速度或持续时间。我们的数据显示了在人类疾病实验模型中麻醉剂对CSD易感性的调节作用，强调了适当的研究设计对于假设检验以及比较研究结果的重要性。
