Institute of Neuroscience, Newcastle University, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
Neuropharmacology. 2013 Jun;69:45-54. doi: 10.1016/j.neuropharm.2012.06.015. Epub 2012 Jun 18.
Inhibitory neuron behaviour is of fundamental importance to epileptic pathophysiology. When inhibition is compromised, such as by GABAergic blockade (Curtis et al., 1970; Connors, 1984; Traub and Miles, 1991) or by shifts in GABAergic reversal potential (Huberfeld et al., 2007), epileptiform discharges occur far more readily. Other studies have shown enhanced inhibition in vivo in the surrounding cortical territories associated with both focal pathological and physiological activity (Prince and Wilder, 1967; Dichter and Spencer, 1969a,b; Goldensohn and Salazar, 1986; Traub and Miles, 1991; Liang and Jones, 1997; Liang et al., 1998; Schwartz and Bonhoeffer, 2001). This gave rise to the concept of an "inhibitory restraint". This concept can explain the often confusing anatomical reorganizations seen in chronically epileptic brains (Sloviter, 1987; Cossart et al., 2001), indicating which changes might be pro-epileptic, and which oppose the epileptic state. It also may explain key electrophysiological features of epileptic seizures. Here we describe current knowledge about the restraint, gleaned mainly from acute pharmacological experiments in animals, both in vivo and in vitro, and speculate how this may alter our understanding of human seizure activity in clinical practice. This article is part of the Special Issue entitled 'New Targets and Approaches to the Treatment of Epilepsy'.
抑制性神经元的行为对癫痫病理生理学至关重要。当抑制作用受到损害时，例如通过 GABA 能阻断（Curtis 等人，1970 年；Connors，1984 年；Traub 和 Miles，1991 年）或 GABA 能反转电位的改变（Huberfeld 等人，2007 年），癫痫样放电就更容易发生。其他研究表明，在与局灶性病理和生理活动相关的周围皮质区域，体内增强了抑制作用（Prince 和 Wilder，1967 年；Dichter 和 Spencer，1969a，b；Goldensohn 和 Salazar，1986 年；Traub 和 Miles，1991 年；Liang 和 Jones，1997 年；Liang 等人，1998 年；Schwartz 和 Bonhoeffer，2001 年）。这就产生了“抑制性约束”的概念。这个概念可以解释在慢性癫痫大脑中经常出现的令人困惑的解剖学重组（Sloviter，1987 年；Cossart 等人，2001 年），表明哪些变化可能是致痫的，哪些变化对抗癫痫状态。它也可能解释癫痫发作的关键电生理特征。在这里，我们主要从动物的急性药理学实验中描述了目前关于这种约束的知识，包括体内和体外实验，并推测这将如何改变我们对临床实践中人类癫痫活动的理解。本文是题为“癫痫治疗的新靶点和新方法”的特刊的一部分。
