title: Targeted suppression of claudin-5             decreases cerebral oedema and improves cognitive outcome following traumatic brain             injury.
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.
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland. matthew.campbell@tcd.ie
authors.forename: Matthew
authors.initials: M
authors.lastname: Campbell
authors.forename: Finnian
authors.initials: F
authors.lastname: Hanrahan
authors.forename: Oliviero L
authors.initials: OL
authors.lastname: Gobbo
authors.forename: Michael E
authors.initials: ME
authors.lastname: Kelly
authors.forename: Anna-Sophia
authors.initials: AS
authors.lastname: Kiang
authors.forename: Marian M
authors.initials: MM
authors.lastname: Humphries
authors.forename: Anh T H
authors.initials: AT
authors.lastname: Nguyen
authors.forename: Ema
authors.initials: E
authors.lastname: Ozaki
authors.forename: James
authors.initials: J
authors.lastname: Keaney
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Blau
authors.forename: Christian M
authors.initials: CM
authors.lastname: Kerskens
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Cahalan
authors.forename: John J
authors.initials: JJ
authors.lastname: Callanan
authors.forename: Eugene
authors.initials: E
authors.lastname: Wallace
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Grant
authors.forename: Colin P
authors.initials: CP
authors.lastname: Doherty
authors.forename: Peter
authors.initials: P
authors.lastname: Humphries
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D001929:Brain Edema / Q000000981:diagnostic imaging / Q000209:etiology* / Q000628:therapy*; D001930:Brain Injuries / Q000150:complications* / Q000000981:diagnostic imaging; D002648:Child; D062507:Claudin-5; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D003071:Cognition / Q000502:physiology*; D006801:Humans; D007427:Intracranial Pressure / Q000502:physiology; D008297:Male; D051379:Mice; D034622:RNA Interference; D014057:Tomography, X-Ray Computed
chemical_list: C107466:CLDN5 protein, human; D062507:Claudin-5; D057167:Claudins