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

本研究旨在探讨脑缺血后血脑屏障(BBB)的功能变化及神经元保护机制。首先，在C57BL/6N小鼠上观察其对双侧颈总动脉结扎(2VO)所致短暂性脑缺血的神经保护作用。其次，研究了一种新型的阳离子血管活性肠肽类似物(CVIP)对通过血脑屏障进入大脑的短暂性脑缺血是否具有神经保护作用。腹腔注射能显著抑制C57BL/6N小鼠2VO再灌流1周后海马区CA1区神经细胞的丢失。静脉注射cVIP(1.0pmoL/kg)。此外，实时荧光定量聚合酶链式反应(TaqMan)和Western印迹分析表明，C57BL/6J小鼠给予cVIP后，缺血脑组织中FGFR1的表达显著增加。用大鼠原位脑灌流结合毛细血管耗竭法测定脑摄取~(125)I-cVIP的结果表明，~(125)&gt；i-cVIP通过血脑屏障转运。结果提示，cVIP通过血脑屏障进入脑内后，可能通过诱导FGFR1发挥神经保护作用。

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.