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

本研究旨在探讨缺血性脑血脑屏障（BBB）的功能变化及其神经元保护机制。首先，观察双侧颈动脉闭塞（2VO）致C57BL/6N脑短暂性缺血的神经保护作用。其次，研究了一种新型阳离子VIP类似物（cVIP）通过血脑屏障摄取后，是否对短暂性脑缺血具有神经保护作用。腹腔注射cVIP （1.0 pmol/kg）可显著抑制C57BL/6N小鼠2vo再灌注后1周海马CA1区神经元细胞的损失。此外，定量实时PCR （TaqMan）和Western blot分析显示，cVIP给药后，FGFR1在C57BL/6J小鼠缺血脑中显著过表达。通过大鼠原位脑灌注结合毛细管耗用法评估^<125>I-cVIP的脑摄取，表明^<125>I-cVIP通过血脑屏障进行了显著的运输。目前的结果表明，cVIP可能通过血脑屏障进入大脑后通过诱导FGFR1表现出神经保护作用。

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.