Functional Changes in the Blood-Brain Barrier and Neuroprotective Effects in the Brain Ischemia

血脑屏障的功能变化和脑缺血的神经保护作用

• 批准号: 16590123
• 负责人: DEGUCHI Yoshiharu
• 金额: $ 2.24万
• 依托单位: Teikyo 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-16590123/
• 关键词: blood-brain barrier; ammonal model for ischemia; delayed neuronal death; bFGF; FGF receptor; FGFRs-expressing cells; stroke; neuroprotection; 脳保護機

This study was to investigate functional changes in the blood-brain barrier (BBB) and mechanism for neuron protection in the ischemic brain. Firstly, the neuroprotective effects was examined in transient brain ischemia induced by bilateral carotid artery occlusion (2VO) in C57BL/6N. Secondly, it was investigated whether a novel cationic VIP analogue (cVIP) has a neuroprotective effect in transient brain ischemia after uptake into the brain through the BBB. A loss of neuronal cells in the hippocampal CA1 region of C57BL/6N mice 1 week after 2VO-reperfusion was significantly suppressed by an i.p. injection of cVIP (1.0 pmol/kg). In addition, the quantitative real-time PCR (TaqMan) and Western blot analyses revealed that FGFR1 was significantly over-expressed in the ischemic brain of C57BL/6J mice after cVIP administration. The brain uptake of ^<125>I-cVIP, evaluated by the in situ rat brain perfusion coupled with the capillary depletion method, showed that ^<125>I-cVIP underwent significant transport through the BBB. The present results suggest that cVIP may exhibit a neuroprotective effect via induction of FGFR1 after uptake into the brain through the BBB.

这项研究是为了研究血脑屏障（BBB）的功能变化和缺血性大脑中神经元保护的机制。首先，在C57BL/6N中的双侧颈动脉闭塞（2VO）诱导的瞬时脑缺血中检查了神经保护作用。其次，已经研究了新型的阳离子VIP类似物（CVIP）是否在通过BBB吸收大脑后，对瞬态脑缺血具有神经保护作用。 2vo-重新灌注后1周，腹腔注射后，C57BL/6N小鼠的海马CA1区域中神经元细胞的丧失被腹腔注射显着抑制。注射CVIP（1.0 pmol/kg）。此外，定量实时PCR（TAQMAN）和Western印迹分析表明，CVIP给药后C57BL/6J小鼠的缺血性大脑中FGFR1明显过表达。 ^<125> i-CVIP的大脑摄取，通过原位大鼠脑灌注与毛细管耗竭法相结合，表明 ^<125> I-CVIP通过BBB进行了大量运输。目前的结果表明，CVIP通过BBB吸收大脑后FGFR1可能会通过诱导FGFR1表现出神经保护作用。

项目成果

Blood-brain barrier permeability of novel [D-Arg^2]dermorphin (1-4) analogues

新型 [D-Arg^2]dermorphin (1-4) 类似物的血脑屏障通透性

• 发表时间: 2004
• 期刊: J. Pharmacol. Exp. Ther. 310(1)
• 作者: Okada;K. et al.;Deguchi Y. et al.
• 通讯作者: Deguchi Y. et al.

Transport of basic peptides at the blood-brain barrier In Handbook of Biologically Active Peptides(Ed. by Abba J.Kastin)

碱性肽在血脑屏障的转运 生物活性肽手册（Abba J.Kastin 编）

• 发表时间: 2006
• 作者: Ishibashi Y;Sugita T;他;Deguchi Y. et al.;Deguchi Y. et al.
• 通讯作者: Deguchi Y. et al.

Transport of basic peptides at the blood-brain barrier

碱性肽在血脑屏障的转运

• 发表时间: 2006
• 期刊: In Handbook of Biologically Active Peptides (Ed. by Abba J.Kastin) (Elsevier, San Diego)
• 作者: Sugita T;他;Deguchi Y. et al.
• 通讯作者: Deguchi Y. et al.

Blood-Brain Barrier Transport and Neuroprotective Effect of a novel cationic VIP analogue

新型阳离子 VIP 类似物的血脑屏障转运和神经保护作用

• 发表时间: 2005
• 期刊: Drug Metabol. Rev. Biotransform. Dispos. Xenobio. 37 Suppl. 2
• 作者: Imaoka;S. et al.;Deguchi Y. et al.
• 通讯作者: Deguchi Y. et al.

In Handbook of Biologically Active Peptides, Et. by Abba J. Kastin, Elsevier, San Diego, pp. 1461-1466.

在《生物活性肽手册》等中。

• 发表时间: 2006
• 作者: Ishibashi Y;Sugita T;他;Deguchi Y. et al.
• 通讯作者: Deguchi Y. et al.