Wang Hwai-Lee, Kuo Eva Yuhua, Lai Ted Weita
Graduate Institute of Clinical Medical Science.
Graduate Institute of Biomedical Sciences.
Neuroreport. 2018 Aug 1;29(11):924-931. doi: 10.1097/WNR.0000000000001052.
Blood-brain barrier (BBB) integrity can be determined by tracer infusion into the circulation followed by measurements of its penetration into the brain parenchyma. Tracer injection through the intraperitoneal (i.p.) route (rather than intravascular injection) avoids confounding effects of animal anesthesia or immobilization/surgical stress. Evans blue dye (EBD) can be administered by i.p. injection, and once in circulation, it binds to plasma albumin to become an endogenous protein tracer. Here, we investigated whether a similar level of EBD is extravasated into the brain following i.p. versus intravenous (i.v.) injection in rats. In comparison with i.v. EBD injection, i.p. EBD injection resulted in much of the tracer residing in the peritoneal cavity. Accordingly, comparatively less EBD was found in the blood, liver, or brain of BBB-intact rat. In addition, following unilateral osmotic BBB disruption, i.v. but not i.p. EBD stained the ipsilateral hemisphere blue. Nevertheless, following either route of tracer administration in these rats, spectrophotometric quantification detected more EBD in the ipsilateral (BBB-disrupted) than in the contralateral hemisphere. Taken together, in contrast to a recent report, we found that i.p. EBD resulted in less tracer in circulation and in peripheral/central organs than EBD delivered i.v. We nevertheless conclude that i.p. EBD delivered sufficient tracer for the detection of regional BBB disruption.
血脑屏障(BBB)的完整性可通过将示踪剂注入循环系统,随后测量其进入脑实质的渗透情况来确定。通过腹腔内(i.p.)途径注射示踪剂(而非血管内注射)可避免动物麻醉或固定/手术应激带来的混杂效应。伊文思蓝染料(EBD)可通过腹腔内注射给药,一旦进入循环,它会与血浆白蛋白结合,成为一种内源性蛋白质示踪剂。在此,我们研究了在大鼠中,腹腔内注射与静脉内(i.v.)注射相比,是否有相似水平的EBD渗入大脑。与静脉内注射EBD相比,腹腔内注射EBD导致大部分示踪剂留在腹腔内。因此,在血脑屏障完整的大鼠的血液、肝脏或大脑中发现的EBD相对较少。此外,在单侧渗透性血脑屏障破坏后,静脉内注射而非腹腔内注射的EBD使同侧半球染成蓝色。然而,在这些大鼠中,无论采用哪种示踪剂给药途径,分光光度法定量检测发现同侧(血脑屏障破坏)半球中的EBD比 contralateral半球中的更多。综上所述,与最近的一份报告相反,我们发现腹腔内注射EBD导致循环系统以及外周/中枢器官中的示踪剂比静脉内注射EBD时更少。尽管如此,我们得出结论,腹腔内注射EBD能提供足够的示踪剂用于检测局部血脑屏障破坏。