title: Ghrelin prevents disruption of the blood-brain barrier after traumatic brain injury.
abstract: Significant effort has been focused on reducing neuronal damage from post-traumatic brain injury (TBI) inflammation and blood-brain barrier (BBB)-mediated edema. The orexigenic hormone ghrelin decreases inflammation in sepsis models, and has recently been shown to be neuroprotective following subarachnoid hemorrhage. We hypothesized that ghrelin modulates cerebral vascular permeability and mediates BBB breakdown following TBI. Using a weight-drop model, TBI was created in three groups of mice: sham, TBI, and TBI/ghrelin. The BBB was investigated by examining its permeability to FITC-dextran and through quantification of perivascualar aquaporin-4 (AQP-4). Finally, we immunoblotted for serum S100B as a marker of brain injury. Compared to sham, TBI caused significant histologic neuronal degeneration, increases in vascular permeability, perivascular expression of AQP-4, and serum levels of S100B. Treatment with ghrelin mitigated these effects; after TBI, ghrelin-treated mice had vascular permeability and perivascular AQP-4 and S100B levels that were similar to sham. Our data suggest that ghrelin prevents BBB disruption after TBI. This is evident by a decrease in vascular permeability that is linked to a decrease in AQP-4. This decrease in vascular permeability may diminish post-TBI brain tissue damage was evident by decreased S100B.
authors.affiliation: Department of Surgery, University of California-San Diego, San Diego, California, USA.
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Lopez
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Krzyzaniak
authors.forename: Chelsea
authors.initials: C
authors.lastname: Blow
authors.forename: James
authors.initials: J
authors.lastname: Putnam
authors.forename: Yan
authors.initials: Y
authors.lastname: Ortiz-Pomales
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Hageny
authors.forename: Brian
authors.initials: B
authors.lastname: Eliceiri
authors.forename: Raul
authors.initials: R
authors.lastname: Coimbra
authors.forename: Vishal
authors.initials: V
authors.lastname: Bansal
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D054439:Ghrelin / Q000502:physiology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D054439:Ghrelin