Study of caudate stimulation on intractable epilepsy

在癫痫实验模型中研究了尾状核在运动或运动前皮层病灶的癫痫发作发展中的作用。慢性大鼠连续8 ~ 10 Hz电刺激运动前皮层诱发电临床发作，电临床发作分为4期。电凝或微量注射muscimol （GABA激动剂）到同侧尾状核增加了诱导每个发作阶段所需的刺激阈值。同侧尾状核损伤后，大鼠运动前皮层点燃的癫痫发展明显受到抑制。另一方面，在同侧尾状核反馈刺激（10hz）下，青霉素对急性期猫运动皮质诱导的间期尖峰数量显著减少。然而，反馈尾状核黏液刺激并没有改变完全持续的发作。电生理学研究表明，纹状体-黑丘回路由两个连续的抑制链接（GABAergic）组成。此外，还存在强大的尾状丘脑抑制通路。观察到的尾状核损伤后的抑制作用，或注射muscimol到尾状核可能是由于这种尾状-黑神经抑制环的破坏，其中黑丘脑抑制变得更强。尾状核反馈刺激对皮层间峰的抑制作用可能来自后一回路。这些发现提示尾状核的功能可能根据癫痫发作的不同状态而变化。我们体内微透析的初步研究表明，在不同的癫痫发作阶段测量尾状核的细胞外神经递质可能是值得的。

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.