Study of caudate stimulation on intractable epilepsy

在癫痫的实验模型中，研究了尾状核在运动或运动前皮质灶癫痫发展中的作用。在慢性大鼠，以8~10赫兹的持续电刺激运动前皮质可引起电临床惊厥，其发作可分为4个阶段。电凝或向同侧尾状核微量注射麝香酚(GABA激动剂)可增加诱发各发作阶段所需的刺激阈值。损毁同侧尾状核后，大鼠运动前皮质点燃癫痫的发展受到显著抑制。另一方面，对同侧尾状核的反馈刺激(10赫兹)可显著减少急性猫运动皮质应用青霉素所引起的发作间期棘波数目。电生理研究表明，纹状体-黑质-丘脑回路由两个连续的抑制环节(GABA能)组成。此外，还有强大的尾状核-丘脑抑制通路。损毁或向尾状核注射蝇草酚后观察到的抑制效应可能是由于尾状核-黑质抑制环被破坏，其中黑质-丘脑的抑制作用变得更强。反馈刺激尾状核对发作间期皮层棘波的抑制作用可能源于后者。这些结果提示，尾状核的功能可能会随着癫痫发作的不同状态而改变。我们用体内微透析进行的初步研究表明，在不同的癫痫发作阶段，尾状核细胞外神经递质的测定可能是值得的。

Roles of the caudate nucleus in seizure developments from the motor or premotor cortical foci were studied in experimental models of epilepsy. In chronic rats, continuous electrical stimulation with 8-10 Hz to the premotor cortex induced electroclinical seizures which were divided into 4 stages. Electrocoagulation or microinjection of muscimol (GABA agonist) to the ipsilateral caudate nucleus increased a stimulus threshold necessary to induce each seizure stage. Seizure developments of the premotor cortical kindling in rats were significantly suppressed following the ipsilateral caudate lesion. On the other hand, numbers of interictal spikes induced by application of penicillin to the motor cortex in acute cats were significantly decreased under the feedback stimulation (10 Hz) to the ipsilateral caudate nucleus. However, feedback caudate mucate stimulation did not modify full-blown sustained paroxysms.Electrophysiological studies suggest that striato-nigro-thalamic circuits are composed-of two successive inhibitory links (GABAergic). Also, there exist powerful caudate-thalamic inhibitory pathways. Observed inhibitory effect following lesion of, or muscimol injection to the caudate nucleus may be due to disruption of this caudate-nigral inhibitory loop in which nigro-thalamic inhibition becomes more powerful. Inhibitory effects of feedback stimulation to the caudate nucleus on interictal cortical spikes may results from the latter circuit. These findings suggest that a functions of the caudate nucleus might be changeable according to various states of seizure.Our preliminary study with in vivo microdialysis showed that measurements of extracellular neurotransmitters in the caudate nucleus during various seizure stage may be worthwhile.