Abstract：
Vasogenic brain edema, a potentially life-threatening consequence following an acute ischemic stroke, is a major clinical problem. This research aims to explore the therapeutic benefits of nimodipine, a calcium channel blocker, in mitigating vasogenic cerebral edema and preserving blood-brain barrier (BBB) function in an ischemic stroke rat model. In this research, animals underwent the induction of ischemic stroke via a 60-minute blockage of the middle cerebral artery and treated with a nonhypotensive dose of nimodipine (1 mg/kg/day) for a duration of five days. The wet/dry method was employed to identify cerebral edema, and the Evans blue dye extravasation technique was used to assess the permeability of the BBB. Furthermore, immunofluorescence staining was utilized to assess the protein expression levels of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). The study also examined mitochondrial function by evaluating mitochondrial swelling, succinate dehydrogenase (SDH) activity, the collapse of mitochondrial membrane potential (MMP), and the generation of reactive oxygen species (ROS). Post-stroke administration of nimodipine led to a significant decrease in cerebral edema and maintained the integrity of the BBB. The protective effects observed were associated with a reduction in cell apoptosis as well as decreased expression of MMP-9 and ICAM-1. Furthermore, nimodipine was observed to reduce mitochondrial swelling and ROS levels while simultaneously restoring MMP and SDH activity. These results suggest that nimodipine may reduce cerebral edema and BBB breakdown caused by ischemia/reperfusion. This effect is potentially mediated through the reduction of MMP-9 and ICAM-1 levels and the enhancement of mitochondrial function.
摘要：
血管源性脑水肿，急性缺血性中风后可能危及生命的后果，是一个主要的临床问题。本研究旨在探索尼莫地平的治疗益处，钙通道阻滞剂,在缺血性中风大鼠模型中减轻血管源性脑水肿和保留血脑屏障（BBB）功能。在这项研究中,动物通过阻断大脑中动脉60分钟诱发缺血性卒中,并接受非低血压剂量的尼莫地平(1mg/kg/天)治疗5天.采用湿/干法鉴定脑水肿，用伊文思蓝染料外渗技术评估血脑屏障的通透性。此外，免疫荧光染色用于评估基质金属蛋白酶-9（MMP-9）和细胞间粘附分子-1（ICAM-1）的蛋白质表达水平。该研究还通过评估线粒体肿胀来检查线粒体功能，琥珀酸脱氢酶（SDH）活性，线粒体膜电位（MMP）的崩溃，和活性氧（ROS）的产生。中风后给予尼莫地平导致脑水肿的显着减少并保持BBB的完整性。观察到的保护作用与细胞凋亡的减少以及MMP-9和ICAM-1表达的减少有关。此外，观察到尼莫地平可降低线粒体肿胀和ROS水平，同时恢复MMP和SDH活性。这些结果表明，尼莫地平可以减轻缺血/再灌注引起的脑水肿和BBB破坏。这种作用可能通过降低MMP-9和ICAM-1水平以及增强线粒体功能来介导。
