Prince D A, Jacobs K
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA 94305-5122, USA.
Epilepsy Res. 1998 Sep;32(1-2):83-92. doi: 10.1016/s0920-1211(98)00042-4.
Although drug-induced disinhibition is a potent method for producing acute epileptogenesis, data with respect to possible disorders of GABAergic inhibitory function in models of chronic epilepsy are incomplete and inconsistent. We examined rat models of cortical post-traumatic epilepsy, and epileptogenic cortical microgyri. Results suggest enhanced rather than decreased inhibitory function in cortical networks in these preparations. In brain slices from epileptogenic chronically isolated cortex, the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) and miniature (m)IPSCs in layer V pyramidal neurons is increased compared to control. In the epileptogenic zone adjacent to the microgyrus, both spontaneous and stimulus-induced IPSCs are larger in amplitude than control, and the frequency of sIPSCs is more dependent upon glutamatergic excitation of interneurons than in control layer V neurons of homotopic cortex. Immunocytochemical studies show that there is enhanced immunoreactivity for several proteins in GABAergic interneurons of chronic cortical isolations, and suggest that there may be sprouting of GABAergic axons in the area of injury. This conclusion is supported by anatomic data showing an approximate doubling of the number of presumed inhibitory synapses on somata of layer V pyramidal neurons. These anatomic findings are consistent with the increased frequency of mIPSCs on these neurons. Inhibition is robust in both of these chronic models of epileptogenesis. Increased inhibitory electrogenesis might be pictured as part of the epileptogenic process, e.g. a mechanism for synchronizing the discharge of pyramidal neurons, or as a compensatory mechanism that might prevent the development of abnormal activities in some cases, or limit the intensity of epileptogenesis in others.
尽管药物诱导的去抑制是引发急性癫痫发生的有效方法，但关于慢性癫痫模型中GABA能抑制功能可能出现的紊乱的数据并不完整且相互矛盾。我们研究了皮质创伤后癫痫大鼠模型以及致痫性皮质微小脑回。结果表明，在这些实验制剂中，皮质网络的抑制功能增强而非减弱。在致痫性慢性孤立皮质的脑片中，与对照组相比，V层锥体神经元的自发性抑制性突触后电流（sIPSCs）和微小（m）IPSCs的频率增加。在微小脑回相邻的致痫区，自发性和刺激诱发的IPSCs的幅度均大于对照组，并且sIPSCs的频率比同型皮质的对照组V层神经元更依赖于中间神经元的谷氨酸能兴奋。免疫细胞化学研究表明，慢性皮质孤立的GABA能中间神经元中几种蛋白质的免疫反应性增强，提示损伤区域可能存在GABA能轴突发芽。这一结论得到解剖学数据的支持，该数据显示V层锥体神经元胞体上假定的抑制性突触数量大约增加了一倍。这些解剖学发现与这些神经元上mIPSCs频率的增加一致。在这两种慢性癫痫发生模型中，抑制作用都很强。抑制性电活动增加可能被视为癫痫发生过程的一部分，例如一种使锥体神经元放电同步的机制，或者在某些情况下可能是一种补偿机制，可防止异常活动的发展，或在其他情况下限制癫痫发生的强度。
