Development of drug delivery system for central nervous system disease using with temperature control devise

使用温度控制装置的中枢神经系统疾病药物输送系统的开发

• 批准号: 22659261
• 负责人: SUZUKI Michiyasu
• 金额: $ 1.96万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22659261/
• 关键词: 血液脳関門; ニューロモデュレーションデバイス; 脳温; ニューロモデュレーション

Drug delivery system(DDS) through blood brain barrier(BBB) promises to enhance the effectiveness of medicine for nervous system diseases such as epilepsy and malignant brain tumors. In order to develop the DDS system, control of BBB permeability of molecules by alteration of temperature was analyzed. Tight junction of artificial BBB made from mouse endothelial cell was temporary opened at 15 degrees centigrade. And claudin5, one of the major structural proteins of the tight junction decreased the amount of expression at 15 degrees. Evans blue administered to a rat vein leaked to the brain surface when it was cooled. The increased permeability was reversible by the temperature control. Indocyanine green administered intravenously to an epilepsy patient appeared to the cooled area of brain surface at the surgery of temporal lobectomy. These results lead that the temperature control may modulate BBB permeability in a reversible fashion.

通过血脑屏障给药系统有望提高癫痫、恶性脑肿瘤等神经系统疾病的药物疗效。为了开发DDS系统，分析了通过改变温度来控制分子的血脑屏障通透性。用小鼠内皮细胞制成的人工血脑屏障在15 ℃下暂时开放紧密连接。而紧密连接的主要结构蛋白之一claudin5在15 ℃时表达量减少。当冷却时，注入大鼠静脉的伊文思蓝泄漏到大脑表面。增加的渗透性通过温度控制是可逆的。一位癫痫病人在接受颞叶切除手术时，静脉注射吲哚菁绿色后，脑部表面出现冷却区。这些结果导致温度控制可以以可逆的方式调节BBB渗透性。

项目成果

Cooling of the epileptic focus suppresses seizures with minimal influence on neurologic functions

• DOI: 10.1111/j.1528-1167.2011.03388.x
• 发表时间: 2012-03-01
• 期刊: EPILEPSIA
• 影响因子: 5.6
• 作者: Fujii, Masami;Inoue, Takao;Suzuki, Michiyasu
• 通讯作者: Suzuki, Michiyasu

温度を用いた中枢神経疾患治療法

利用温度治疗中枢神经系统疾病

• 发表时间: 2010
• 作者: Lim Y;Yamanari M;Miura M;Oshika T;Yasuno Y;Nishimoto K;吉田秀樹,宮地 充,土屋邦彦,家原知子,細井 創;Kyoko Ohno-Matsui;鈴木倫保
• 通讯作者: 鈴木倫保

Intra-operative monitoring of lower extremity motor-evoked potentials by direct cortical stimulation

• DOI: 10.1016/j.clinph.2011.09.025
• 发表时间: 2012-06-01
• 期刊: CLINICAL NEUROPHYSIOLOGY
• 影响因子: 4.7
• 作者: Maruta, Yuichi;Fujii, Masami;Suzuki, Michiyasu
• 通讯作者: Suzuki, Michiyasu

Cooling of the epileptic focus suppresses seizures with minimal influence on neurological functions

癫痫病灶的冷却可抑制癫痫发作，同时对神经功能的影响极小

• 发表时间: 2011
• 作者: Masami Fujii;Takao Inoue;Sadahiro Nomura;Yuichi Yuichi Maruta;Yeting He;Tatsuji Tatsuji Tokiwa;Toshitaka Yamakawa;Yuji Owada;Takeshi Yamakawa;Michiyasu Suzuki
• 通讯作者: Michiyasu Suzuki

Alterative treatment of intractable epilepsy with focal brain cooling-A review of our past atudies-

局灶性脑冷却治疗顽固性癫痫的替代治疗-我们过去研究的回顾-

• 发表时间: 2011
• 作者: Satoh;T.;Takeuchi;O.;Vandenbon;A.;Yasuda;K.;Kumagai;Y.;Miyake;T.;Matsuyama;T.;Yui;K.;Okazaki;T.;Saitoh;T.;Honma;K.;Nakai;K.;Akira;S.;Masami Fujii
• 通讯作者: Masami Fujii