Intrathecal injection, drugs transporting along perivascular spaces, represents an important route for maintaining blood-brain barrier (BBB) integrity after cerebral ischemia/reperfusion (I/R) injury. However, after being directly injected into cerebrospinal fluid (CSF), the temporal and spatial changes in the distribution of therapeutic protein drugs have remained unknown. Here, with positron emission tomography (PET) imaging, the uptake of 89Zr-agrin is noninvasively and dynamically monitored. These data demonstrate the time-activity curve of drugs in the brain subregions and their spatial distribution in different organs after intrathecal administration. Furthermore, agrin treatment effectively inhibits BBB disruption by reducing the loss of tight-junctional proteins. Importantly, the infarct volume is reduced; the number of apoptotic neurons is decreased; and neurological function is improved in mouse I/R injury models. Thus, intrathecal injection of agrin provides the basis for a new strategy to research and develop protein drugs for reducing the aggravation of I/R injury.

中文翻译：

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鞘内注射后Agrin的时空分布及其在脑缺血/再灌注损伤中的保护作用。

鞘内注射是沿血管周围空间运输的药物，是维持脑缺血/再灌注（I / R）损伤后血脑屏障（BBB）完整性的重要途径。然而，在直接注射入脑脊液（CSF）后，治疗性蛋白药物分布的时空变化仍然未知。在这里，通过正电子发射断层扫描（PET）成像，可以无创且动态地监测89Zr-agrin的摄取。这些数据证明了鞘内给药后，大脑亚区域中药物的时间活性曲线及其在不同器官中的空间分布。此外，凝集素处理可通过减少紧密连接蛋白的损失来有效抑制BBB的破坏。重要的是，减少了梗塞的数量。凋亡神经元数量减少；在小鼠I / R损伤模型中神经功能得到改善。因此，鞘内注射凝集素为研究和开发减少I / R损伤加重的蛋白药物的新策略提供了基础。