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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Campbell, M; Hanrahan, F; Gobbo, OL; Kelly, ME; Kiang, A-S; Humphries, MM; Nguyen, ATH; Ozaki, E; Keaney, J; Blau, CW; Kerskens, CM; Cahalan, SD; Callanan, JJ; Wallace, E; Grant, GA; Doherty, CP; Humphries, P

Published Date

  • May 22, 2012

Published In

Volume / Issue

  • 3 /

Start / End Page

  • 849 -

PubMed ID

  • 22617289

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms1852

Language

  • eng

Conference Location

  • England