Journal
NEUROREPORT
Volume 29, Issue 11, Pages 924-931Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/WNR.0000000000001052
Keywords
blood-brain barrier; Evans blue dye; intraperitoneal injection; rat; route of administration
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Funding
- China Medical University Hospital [DMR-104-079]
- Ministry of Science and Technology [MOST106-2320-B-039-033]
- National Health Research Institutes [NHRI-EX106-10412NC]
- 'Drug Development Center, China Medical University' from The Featured Areas Research Center Program of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan
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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.
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