外渗
血脑屏障
磁共振成像
缺血
胶束
医学
磁共振造影剂
病理
放射科
化学
中枢神经系统
内科学
物理化学
水溶液
作者
Koji Shiraishi,Zuojun Wang,Daisuke Kokuryo,Ichio Aoki,Masayuki Yokoyama
标识
DOI:10.1016/j.jconrel.2017.03.020
摘要
Blood–brain barrier (BBB) opening is a key phenomenon for understanding ischemia-reperfusion injuries that are directly linked to hemorrhagic transformation. The recombinant human tissue-type plasminogen activator (rtPA) increases the risk of symptomatic intracranial hemorrhages. Recent imaging technologies have advanced our understanding of pathological BBB disorders; however, an ongoing challenge in the pre-“rtPA treatment” stage is the task of developing a rigorous method for hemorrhage-risk assessments. Therefore, we examined a novel method for assessment of rtPA-extravasation through a hyper-permeable BBB. To examine the image diagnosis of rtPA-extravasation for a rat transient occlusion-reperfusion model, in this study we used a polymeric micelle MRI contrast-agent (Gd-micelles). Specifically, we used two MRI contrast agents at 1 h after reperfusion. Gd-micelles provided very clear contrast images in 15.5 ± 10.3% of the ischemic hemisphere at 30 min after i.v. injection, whereas a classic gadolinium chelate MRI contrast agent provided no satisfactorily clear images. The obtained images indicate both the hyper-permeable BBB area for macromolecules and the distribution area of macromolecules in the ischemic hemisphere. Owing to their large molecular weight, Gd-micelles remained in the ischemic hemisphere through the hyper-permeable BBB. Our results indicate the feasibility of a novel clinical diagnosis for evaluating rtPA-related hemorrhage risks.
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