Water permeabilities of neural cells and capillaries in brain : Using claudin-5 knocked out mice and H-1 MRI

大脑中神经细胞和毛细血管的水渗透性：使用claudin-5基因敲除小鼠和H-1 MRI

• 批准号: 16590167
• 负责人: SEO Yoshiteru
• 金额: $ 2.24万
• 依托单位: Dokkyo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590167/
• 关键词: brain capillary; water permeability; NMR; relaxation reagent; tight junction; claudin; diffusional anisotropy

The water permeability of capillaries and neural cells in the brain were analyzed by using claudin-t knocked out mice and H-1 MRI. The anatomic basis for blood-brain barrier (BBB) resides in tight junctions (TJs) of brain endothelial cells in addition to their limited transcytosis. The claudin-5 was identified as a major TJ cell adhesion molecule in brain endothelial cells. Three relaxation reagents (ca. 700Da - 17kDa) were applied to estimate water permeability of the neurons/glia cells and BBB in mice. In the intact mice, the longitudinal relaxation rates (1/T_1) showed minimal changes (<0.1 s^<-1>) even the 1/T_1 of blood water was accelerated more than 40 s^<-1> by using the 3 reagents. It is suggested that the normal BBB have very low water permeability. In the claudin-5 knocked out mice, Gd-DTPA^<2-> can pass through the modified BBB. From the dose-dependency of Gd-DTPA, a water efflux rate from the neurons/glia cells was detected which is corresponding to a diffusional water permeability of 1.5-1.0cm s^<-1>. The relaxation reagents (bigger than 2kDa) could not pass through the modified BBB. From the dose-dependency of a relaxation reagent, a water efflux rate from the BBB was detected which is corresponding to a moderate range of diffusional water permeability. These findings provide a new insight on the molecular biology of BBB, and also represent usefulness of this method to monitor physiological parameters of genetically modified animals.

用claudin-t基因敲除小鼠和H-1 MRI分析脑内毛细血管和神经细胞的水渗透性。血脑屏障（BBB）的解剖学基础在于脑内皮细胞的紧密连接（TJ）以及它们有限的胞吞转运。claudin-5被鉴定为脑内皮细胞中主要的TJ细胞粘附分子。三种弛豫试剂（ca. 700Da -17 kDa）测定小鼠神经元/胶质细胞和血脑屏障的透水性。在正常小鼠中，即使使用3种试剂使血液的1/T_1加速超过40 s^，纵向松弛率（1/T_1）的变化也很小（&lt;0.1 s^<-1>）<-1>。正常血脑屏障的透水性很低。在claudin-5敲除的小鼠中，Gd-DTPA-4<2->可以通过修饰的BBB。根据Gd-DTPA的剂量依赖性，检测到神经元/胶质细胞的水流出速率，其对应于1.5-1.0cm·s-1的扩散水渗透率<-1>。松弛剂（大于2kDa）无法通过修饰后的血脑屏障。从松弛剂的剂量依赖性，从血脑屏障的水流出率被检测到，这是对应于一个中等范围的扩散水渗透性。这些发现为BBB的分子生物学提供了新的见解，也代表了该方法在监测转基因动物生理参数方面的有用性。

项目成果

MRIによる生体イメージング-生理機能の画像化と定量

使用 MRI 进行生物成像 - 生理功能的成像和量化

• 发表时间: 2005
• 期刊: バイオテクノロジージャーナル 5(3)
• 作者: SAKAI;T;瀬尾 芳輝
• 通讯作者: 瀬尾 芳輝

Bioimaging by using MRI

使用 MRI 进行生物成像

• 发表时间: 2005
• 期刊: Biotechnology Journal 5(3)
• 作者: Hamada H;Ishiguro H;Yamamoto A;Shimano-Futakuchi S;Ko SB;Yoshikawa T;Goto H;Kitagawa M;Hayakawa T;Seo Y;Naruse S;桑木共之;Niiyama S. et al.;Yoshiteru Seo
• 通讯作者: Yoshiteru Seo