Schwartzkroin P A
Adv Neurol. 1986;44:991-1010.
Many models of epileptiform activity have been developed using in vitro slices, particularly the in vitro hippocampal slice preparation. Using this preparation, investigators have elucidated some of the intrinsic neuronal and synaptic properties that appear to be involved in the generation of burst activity and hyperexcitability typical of epileptic brain. A variety of potassium and calcium conductances, in dendritic as well as somatic membrane, have been found in hippocampal neurons that produce burst discharges; appropriate channel blockers can modulate the firing patterns of these neurons. Receptor antagonists, particularly those which interact with the gamma-aminobutyric acid (GABA) receptor-chloride channel complex, have also been found to be very effective in producing epileptiform activity in the reduced central nervous system (CNS) slice preparation. In most acutely produced epileptogenic slice tissues, it appears that blockade of inhibition, intrinsic mechanisms of excitability, and recurrent excitatory synaptic connections interact to synchronize the cell population. Slice preparations of brain tissue taken from epileptic foci induced in chronic animals have been studied. The kainic acid model, kindling model, and other chronic models of epileptiform activity (alumina gel, freeze lesions) have been studied in vitro; results of these studies suggest that in these tissues there is an alteration in PSP efficacy. Seizure sensitivity in immature CNS tissue may also be produced, in part, by a late development of inhibitory postsynaptic potentials (IPSPs). Studies of cortical slices taken from human epileptic brain during surgery for intractable seizures have begun to reveal some interesting clues about cellular mechanisms underlying discharge in abnormal tissue. Spontaneous, rhythmic post-synaptic potential (PSP) activity has been recorded particularly in slices taken from mesial temporal lobe structures involved in epileptic foci. It is still unclear, however, whether such activity is a reflection of epileptogenicity of this tissue, or is rather characteristic of even normal tissue from mesial temporal cortex. We have learned much about the cellular and synaptic properties of CNS neurons using the in vitro slice preparation and have developed a variety of animal preparations in which we can model epileptiform activity. However, it is still unclear if any of these preparations accurately model human epileptiform abnormalities. A major challenge for modern epilepsy research is to build a bridge between experimental animal models of epilepsy and the epilepsies that occur in the clinical human population.
人们利用体外脑片，特别是体外海马脑片制备技术，开发出了许多癫痫样活动模型。借助这种制备技术，研究人员阐明了一些似乎与癫痫性脑典型的爆发活动和过度兴奋的产生有关的内在神经元和突触特性。在产生爆发性放电的海马神经元中，已发现树突和体细胞膜中存在多种钾离子和钙离子电导；合适的通道阻滞剂可调节这些神经元的放电模式。还发现受体拮抗剂，尤其是那些与γ-氨基丁酸（GABA）受体-氯离子通道复合物相互作用的拮抗剂，在简化的中枢神经系统（CNS）脑片制备中产生癫痫样活动方面非常有效。在大多数急性产生的致痫性脑片组织中，似乎抑制的阻断、兴奋性的内在机制和反复的兴奋性突触连接相互作用，使细胞群同步。对取自慢性动物诱发的癫痫病灶的脑组织切片制备进行了研究。已在体外研究了海藻酸模型、点燃模型和其他癫痫样活动的慢性模型（氧化铝凝胶、冷冻损伤）；这些研究结果表明，在这些组织中，突触后电位（PSP）的效能发生了改变。未成熟中枢神经系统组织中的癫痫发作敏感性，也可能部分是由抑制性突触后电位（IPSP）的后期发育引起的。对在难治性癫痫手术期间取自人类癫痫脑的皮质切片的研究，已开始揭示一些关于异常组织中放电的细胞机制的有趣线索。特别是在取自涉及癫痫病灶的内侧颞叶结构的切片中，记录到了自发的、有节律的突触后电位（PSP）活动。然而，目前仍不清楚这种活动是该组织致痫性的反映，还是内侧颞叶皮质正常组织的特征。利用体外脑片制备技术，我们已经了解了很多关于中枢神经系统神经元的细胞和突触特性，并开发了多种可以模拟癫痫样活动的动物制备模型。然而，目前仍不清楚这些制备模型是否能准确模拟人类癫痫样异常。现代癫痫研究的一个主要挑战是在癫痫的实验动物模型与临床人群中发生的癫痫之间架起一座桥梁。
