An Unexpected Transient Breakdown of the Blood Brain Barrier Triggers Passage of Large Intravenously Administered Nanoparticles

Nicole Smith, I. Gachulincova, Diwei Ho, Charlotte Bailey, Carole Bartlett, Marck Norret, John Murphy, Alysia Buckley, Paul Rigby, Mike House, Tim St Pierre, Melinda Fitzgerald, Killugudi Swaminatha Iyer, Sarah Dunlop

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The highly restrictive blood-brain barrier (BBB) plays a critically important role in maintaining brain homeostasis and is pivotal for proper neuronal function. The BBB is currently considered the main limiting factor restricting the passage of large (up to 200 nm) intravenously administered nanoparticles to the brain. Breakdown of the barrier occurs as a consequence of cerebrovascular diseases and traumatic brain injury. In this article, we report that remote injuries in the CNS are also associated with BBB dysfunction. In particular, we show that a focal partial transection of the optic nerve triggers a previously unknown transient opening of the mammalian BBB that occurs in the visual centres. Importantly, we demonstrate that this transient BBB breakdown results in a dramatic change in the biodistribution of intravenously administered large polymeric nanoparticles which were previously deemed as BBB-impermeable.
Original languageEnglish
Article number22595
Pages (from-to)1-9
Number of pages9
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 4 Mar 2016

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