Phosphatidylserine-microbubble targeting-activated microglia/macrophage in inflammation combined with ultrasound for breaking through the blood–brain barrier

作者：Ranran Zhao, Jie Jiang, Huiwen Li, Min Chen, Renfa Liu, Sujuan Sun, De Ma, Xiaolong Liang, Shumin Wang · 发表于：Journal of Neuroinflammation · 年份：2018 · DOI：10.1186/s12974-018-1368-1 · 被引用次数：46 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Ultrasound and Hyperthermia Applications、Barrier Structure and Function Studies

BACKGROUND AND PURPOSE: Inflammatory reaction plays a crucial role in cerebral ischemia reperfusion (IR) injury. It has been shown that activated microglia long-term existed in cerebral ischemia and induced second injury. Therefore, we hypothesize that prepared phosphatidylserine (PS)-modified microbubbles (PS-MBs) combined with ultrasound-targeted microbubble destruction (UTMD) can safely open the blood-brain barrier (BBB) and target activated microglia for inflammatory area in the later stage of ischemia reperfusion. METHODS: To verify our hypothesis, rat model of IR was established, then the change of activated microglia/macrophage (M/M) and permeability of BBB at 1, 7, 14, and 21 days could be clearly observed post IR. And the activated M/M still can be observed during the whole experiment. RESULTS: The Evans blue extravasation of BBB gradually declined from day 1 to day 21. Compared to the control group, microbubbles containing PS were taken up more by activated M/M (approximately twofold) both in vitro and in vivo. CONCLUSIONS: PS-MBs combined with ultrasound (US) exposure could safely open BBB, and the resulting PS nanoparticles (PS-NPs) could further target activated M/M in the neuroinflammation.