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

© 2016 The Authors. 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) intravenous...

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Main Authors: Smith, N.M., Gachulincova, I., Ho, D., Bailey, C., Bartlett, C.A., Norret, M., Murphy, J., Buckley, A., Rigby, P.J., House, M.J., Pierre, T.S., Fitzgerald, Melinda, Iyer, K.S., Dunlop, S.A.
Format: Journal Article
Language:English
Published: NATURE PUBLISHING GROUP 2016
Subjects:
Online Access:http://purl.org/au-research/grants/nhmrc/1028681
http://hdl.handle.net/20.500.11937/81495
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author Smith, N.M.
Gachulincova, I.
Ho, D.
Bailey, C.
Bartlett, C.A.
Norret, M.
Murphy, J.
Buckley, A.
Rigby, P.J.
House, M.J.
Pierre, T.S.
Fitzgerald, Melinda
Iyer, K.S.
Dunlop, S.A.
author_facet Smith, N.M.
Gachulincova, I.
Ho, D.
Bailey, C.
Bartlett, C.A.
Norret, M.
Murphy, J.
Buckley, A.
Rigby, P.J.
House, M.J.
Pierre, T.S.
Fitzgerald, Melinda
Iyer, K.S.
Dunlop, S.A.
author_sort Smith, N.M.
building Curtin Institutional Repository
collection Online Access
description © 2016 The Authors. 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.
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spelling curtin-20.500.11937-814952020-11-03T01:53:21Z An Unexpected Transient Breakdown of the Blood Brain Barrier Triggers Passage of Large Intravenously Administered Nanoparticles Smith, N.M. Gachulincova, I. Ho, D. Bailey, C. Bartlett, C.A. Norret, M. Murphy, J. Buckley, A. Rigby, P.J. House, M.J. Pierre, T.S. Fitzgerald, Melinda Iyer, K.S. Dunlop, S.A. Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics CENTRAL-NERVOUS-SYSTEM SECONDARY DEGENERATION IN-VIVO NEUROLOGICAL DISEASES DELIVERY INJURY CONTRIBUTE TRANSPORT IMMUNE DRUGS © 2016 The Authors. 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. 2016 Journal Article http://hdl.handle.net/20.500.11937/81495 10.1038/srep22595 English http://purl.org/au-research/grants/nhmrc/1028681 http://purl.org/au-research/grants/nhmrc/1087114 http://creativecommons.org/licenses/by/4.0/ NATURE PUBLISHING GROUP fulltext
spellingShingle Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CENTRAL-NERVOUS-SYSTEM
SECONDARY DEGENERATION
IN-VIVO
NEUROLOGICAL DISEASES
DELIVERY
INJURY
CONTRIBUTE
TRANSPORT
IMMUNE
DRUGS
Smith, N.M.
Gachulincova, I.
Ho, D.
Bailey, C.
Bartlett, C.A.
Norret, M.
Murphy, J.
Buckley, A.
Rigby, P.J.
House, M.J.
Pierre, T.S.
Fitzgerald, Melinda
Iyer, K.S.
Dunlop, S.A.
An Unexpected Transient Breakdown of the Blood Brain Barrier Triggers Passage of Large Intravenously Administered Nanoparticles
title An Unexpected Transient Breakdown of the Blood Brain Barrier Triggers Passage of Large Intravenously Administered Nanoparticles
title_full An Unexpected Transient Breakdown of the Blood Brain Barrier Triggers Passage of Large Intravenously Administered Nanoparticles
title_fullStr An Unexpected Transient Breakdown of the Blood Brain Barrier Triggers Passage of Large Intravenously Administered Nanoparticles
title_full_unstemmed An Unexpected Transient Breakdown of the Blood Brain Barrier Triggers Passage of Large Intravenously Administered Nanoparticles
title_short An Unexpected Transient Breakdown of the Blood Brain Barrier Triggers Passage of Large Intravenously Administered Nanoparticles
title_sort unexpected transient breakdown of the blood brain barrier triggers passage of large intravenously administered nanoparticles
topic Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CENTRAL-NERVOUS-SYSTEM
SECONDARY DEGENERATION
IN-VIVO
NEUROLOGICAL DISEASES
DELIVERY
INJURY
CONTRIBUTE
TRANSPORT
IMMUNE
DRUGS
url http://purl.org/au-research/grants/nhmrc/1028681
http://purl.org/au-research/grants/nhmrc/1028681
http://hdl.handle.net/20.500.11937/81495