title: An Unexpected Transient Breakdown of the Blood Brain Barrier Triggers Passage of Large Intravenously Administered Nanoparticles.
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.
authors.affiliation: Experimental and Regenerative Neurosciences, School of Animal Biology, The University of Western Australia, Perth, WA 6009, Australia.|School of Chemistry and Biochemistry, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Smith
authors.affiliation: Experimental and Regenerative Neurosciences, School of Animal Biology, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Gachulincova
authors.affiliation: School of Chemistry and Biochemistry, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Diwei
authors.initials: D
authors.lastname: Ho
authors.affiliation: Experimental and Regenerative Neurosciences, School of Animal Biology, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Bailey
authors.affiliation: Experimental and Regenerative Neurosciences, School of Animal Biology, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Carole A
authors.initials: CA
authors.lastname: Bartlett
authors.affiliation: School of Chemistry and Biochemistry, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Marck
authors.initials: M
authors.lastname: Norret
authors.affiliation: Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Murphy
authors.affiliation: Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Alysia
authors.initials: A
authors.lastname: Buckley
authors.affiliation: Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Rigby
authors.affiliation: School of Physics, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: House
authors.affiliation: School of Physics, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Timothy
authors.initials: T
authors.lastname: St Pierre
authors.affiliation: Experimental and Regenerative Neurosciences, School of Animal Biology, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Melinda
authors.initials: M
authors.lastname: Fitzgerald
authors.affiliation: School of Chemistry and Biochemistry, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: K Swaminathan
authors.initials: KS
authors.lastname: Iyer
authors.affiliation: Experimental and Regenerative Neurosciences, School of Animal Biology, The University of Western Australia, Perth, WA 6009, Australia.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Dunlop
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001927:Brain Diseases / Q000503:physiopathology* / Q000601:surgery; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D053758:Nanoparticles / Q000378:metabolism*; D009900:Optic Nerve / Q000473:pathology* / Q000601:surgery; D020221:Optic Nerve Injuries; D011108:Polymers / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
chemical_list: D011108:Polymers