Effect of Basal Ganglia upon Epileptic Seizures in Animal Mode

动物模式下基底神经节对癫痫发作的影响

• 批准号: 15390427
• 负责人: TANAKA Tatsuya
• 金额: $ 4.22万
• 依托单位: School of Medicine Asahikawa medical college
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390427/
• 关键词: Kainic acid; Basak ganglia; Globus pallidus; Deep brain stimulation; Intractable Epilepsy; Experimental epilpesy; 視床下核; 深部脳電気刺激; てんかん発作; ムシモール

Inhibitory and excitatory effects of basal ganglia and subthalamic nuclei were studied using kainic acid -induced seizure model in rats. Cortical epileptogenic foci were induced by intracortical microinjections of kainic acid. In Experiment 1, rats with a cortical focus, induced seizures were well suppressed by high frequency electrical stimulation of bilateral subthalamic nuclei (STN). In experiment 2, muscimol was injected into bilateral STN in rats with cortical focus. After injection, seizures were suppressed. The result suggested inhibition of the bilateral STN resulted in in activation of substantia nigra pars reticulate and seizures reduced.In experiment 3, kainic acid microinjection was performed into unilateral medial globus pallidus (GP) in rats. Each injection resulted in partial epilepsy with secondarily generalized tonic-clonic convulsions. As GP receives fibers from cerebral cortex, its excessive excitation facilitated the epileptic seizure propagation. In experiment 4, kainic acid microinjection into unilateral center-median nucleus of the thalamus (CM) resulted in partial seizures in the center-lateral limbs with secondarily generalized seizures. The results indicated that both GP and CM facilitated the epileptic seizure, both structures will be a good target to put depth electrodes for deep brain stimulations (DBS) in order to perform seizure suppression. Since DBS is less invasive treatment for intractable epilepsy patients, next step of our research is the DBS of GP and CM in kainic acid induced seizures to open clinical application of the DBS.

采用kainic酸诱发大鼠癫痫模型，研究了基底节区和丘脑底核的抑制和兴奋作用。皮质内微量注射kainic酸诱导皮层致痫灶。在实验1中，高频电刺激双侧丘脑下核（STN）能很好地抑制皮质灶大鼠诱发的癫痫发作。实验2：在皮质灶大鼠双侧STN内注射muscimol。注射后癫痫发作得到抑制。结果表明，抑制双侧STN导致网状黑质活化，癫痫发作减少。实验三：在大鼠单侧内侧苍白球（GP）内注射kainic酸。每次注射导致部分癫痫伴继发性全身性强直-阵挛性抽搐。由于GP接收来自大脑皮层的纤维，其过度兴奋促进了癫痫发作的传播。在实验4中，向丘脑单侧中央-正中核（CM）注射海碱酸，导致中外侧肢体部分性癫痫发作，继发全身性癫痫发作。结果表明，GP和CM结构均能促进癫痫的发作，这两个结构都是放置深度电极进行深部脑刺激（DBS）以抑制癫痫发作的良好目标。由于DBS对顽固性癫痫患者的治疗创伤较小，我们下一步的研究是将GP和CM的DBS应用于kainic酸诱导的癫痫发作，开启DBS的临床应用。

项目成果

Clinical application of experimental cortical dysplasia in rats

大鼠实验性皮质发育不良的临床应用

• 发表时间: 2005
• 期刊: Journal of Child Neurology (in press)
• 作者: Takenaka;K.;Hasegawa;S.et al.;Tanaka T
• 通讯作者: Tanaka T

Deep brain stimulation in kainic acid-induced focal seizure

深部脑刺激在红藻氨酸诱导的局灶性癫痫发作中的应用

• 发表时间: 2004
• 期刊: Epilepsia 45(suppl.3)
• 作者: Kato I;et al.;Tanaka T
• 通讯作者: Tanaka T

ラット中大脳動脈閉塞モデルにおけるエダラボンの定位的脳内注入の効果: preliminary report

立体定向脑内注射依达拉奉对大鼠大脑中动脉闭塞模型的影响：初步报告

• 发表时间: 2004
• 期刊: 旭川てんかん外科研究 vol.III 3
• 作者: Hiroaki Osada;Hiroaki Osada;Hiroaki Osada;Hisashi Tsukada;Hisashi Tsukada;Hisashi Tsukada;Tanaka T;程塚 明;中井啓文;櫻井寿郎;橋詰清隆;Tanaka T;Hashizume K;Tanaka T;Tanaka T;Hashizume K;Tanaka T;Hashizume K;Tanaka T;Hashizume K;Tanaka T;Hashizume K;櫻井寿郎
• 通讯作者: 櫻井寿郎

Experimental callosotomy : Electrophysiological and Metabolic approach

实验性胼胝体切开术：电生理学和代谢方法

• 发表时间: 2004
• 期刊: Epilepsia 45(suppl.7)
• 作者: Akatsu T;Wakabayashi G;Aiura K;Suganuma K;Takigawa Y;Wada M;Kawachi S;Tanabe M;Ueda M;Shimazu M;Sakamoto M;Kitajima M.;Tanaka T
• 通讯作者: Tanaka T

飯沼一宇, 呉 繁夫, 田中達也, 佐藤康二: "けいれん発作研究の進歩-乳幼児期に生じるけいれん発作の病体と治療に関する研究 編者:杉田秀夫、高橋清久、脳科学研究の現状と課題"(株)じほう. 201-216 (2003)

Kazuu Iinuma、Shigeo Kure、Tatsuya Tanaka、Koji Sato：“惊厥性癫痫发作的研究进展 - 婴儿期惊厥性癫痫发作的病理学和治疗研究。编辑：Hideo Sugita、Kiyohisa Takahashi，脑科学研究的现状和问题” (Inc.) Jiho. 201-216 (2003)