Targeted suppression of claudin-5 decreases cerebral oedema and improves cognitive outcome following traumatic brain injury

Matthew Campbell (), Finnian Hanrahan, Oliviero L. Gobbo, Michael E. Kelly, Anna-Sophia Kiang, Marian M. Humphries, Anh T.H. Nguyen, Ema Ozaki, James Keaney, Christoph W. Blau, Christian M. Kerskens, Stephen D. Cahalan, John J. Callanan, Eugene Wallace, Gerald A. Grant, Colin P. Doherty and Peter Humphries
Additional contact information
Matthew Campbell: Smurfit Institute of Genetics, Trinity College Dublin
Finnian Hanrahan: Smurfit Institute of Genetics, Trinity College Dublin
Oliviero L. Gobbo: School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin
Michael E. Kelly: FMRIB Centre, University of Oxford, John Radcliffe Hospital
Anna-Sophia Kiang: Smurfit Institute of Genetics, Trinity College Dublin
Marian M. Humphries: Smurfit Institute of Genetics, Trinity College Dublin
Anh T.H. Nguyen: Smurfit Institute of Genetics, Trinity College Dublin
Ema Ozaki: Smurfit Institute of Genetics, Trinity College Dublin
James Keaney: Smurfit Institute of Genetics, Trinity College Dublin
Christoph W. Blau: Smurfit Institute of Genetics, Trinity College Dublin
Christian M. Kerskens: Trinity College Institute of Neuroscience, Lloyd building, Trinity College Dublin
Stephen D. Cahalan: UCD School of Veterinary Medicine & Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
John J. Callanan: UCD School of Veterinary Medicine & Conway Institute of Biomolecular & Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
Eugene Wallace: Health Care Centre, Hospital 5, St James's Hospital
Gerald A. Grant: Duke University Medical Center
Colin P. Doherty: Health Care Centre, Hospital 5, St James's Hospital
Peter Humphries: Smurfit Institute of Genetics, Trinity College Dublin

Nature Communications, 2012, vol. 3, issue 1, 1-12

Abstract: Abstract Traumatic brain injury is the leading cause of death in children and young adults globally. Malignant cerebral oedema has a major role in the pathophysiology that evolves after severe traumatic brain injury. Added to this is the significant morbidity and mortality from cerebral oedema associated with acute stroke, hypoxic ischemic coma, neurological cancers and brain infection. Therapeutic strategies to prevent cerebral oedema are limited and, if brain swelling persists, the risks of permanent brain damage or mortality are greatly exacerbated. Here we show that a temporary and size-selective modulation of the blood-brain barrier allows enhanced movement of water from the brain to the blood and significantly impacts on brain swelling. We also show cognitive improvement in mice with focal cerebral oedema following administration in these animals of short interfering RNA directed against claudin-5. These observations may have profound consequences for early intervention in cases of traumatic brain injury, or indeed any neurological condition where cerebral oedema is the hallmark pathology.

Date: 2012
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms1852 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1852

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms1852

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().