title: The hormone ghrelin prevents traumatic brain injury induced intestinal dysfunction.
abstract: Intestinal barrier breakdown following traumatic brain injury (TBI) is characterized by increased intestinal permeability, leading to bacterial translocation, and inflammation. The hormone ghrelin may prevent intestinal injury and have anti-inflammatory properties. We hypothesized that exogenous ghrelin prevents intestinal injury following TBI. A weight-drop model created severe TBI in three groups of anesthetized Balb/c mice. Group TBI: animals underwent TBI only; Group TBI/ghrelin: animals were given 10 μg of ghrelin intraperitoneally prior and 1 h following TBI; Group sham: no TBI or ghrelin injection. Intestinal permeability was measured 6 h following TBI by detecting serum levels of FITC-Dextran after injection into the intact ileum. The terminal ileum was harvested for histology, expression of the tight junction protein MLCK and inflammatory cytokine TNF-α. Permeability increased in the TBI group compared to the sham group (109.7 ± 21.8 μg/mL vs. 32.2 ± 10.1 μg/mL; p < 0.002). Ghrelin prevented TBI-induced permeability (28.3 ± 4.2 μg/mL vs. 109.7 ± 21.8 μg/mL; p < 0.001). The intestines of the TBI group showed blunting and necrosis of villi compared to the sham group, while ghrelin injection preserved intestinal architecture. Intestinal MLCK increased 73% compared to the sham group (p < 0.03). Ghrelin prevented TBI-induced MLCK expression to sham levels. Intestinal TNF-α increased following TBI compared to the sham group (46.2 ± 7.1 pg/mL vs. 24.4 ± 2.2 pg/mL p < 0.001). Ghrelin reduced TNF-α to sham levels (29.2 ± 5.0 pg/mL; p = NS). We therefore conclude that ghrelin prevents TBI-induced injury, as determined by intestinal permeability, histology, and intestinal levels of TNF-α. The mechanism for ghrelin mediating intestinal protection is likely multifactorial, and further studies are needed to delineate these possibilities.
authors.affiliation: Department of Surgery, Division of Trauma, Surgical Critical Care and Burns, University of California San Diego, San Diego, California 92103, USA.
authors.forename: Vishal
authors.initials: V
authors.lastname: Bansal
authors.forename: Seok Yong
authors.initials: SY
authors.lastname: Ryu
authors.forename: Chelsea
authors.initials: C
authors.lastname: Blow
authors.forename: Todd
authors.initials: T
authors.lastname: Costantini
authors.forename: William
authors.initials: W
authors.lastname: Loomis
authors.forename: Brian
authors.initials: B
authors.lastname: Eliceiri
authors.forename: Andrew
authors.initials: A
authors.lastname: Baird
authors.forename: Paul
authors.initials: P
authors.lastname: Wolf
authors.forename: Raul
authors.initials: R
authors.lastname: Coimbra
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D054439:Ghrelin / Q000627:therapeutic use*; D007082:Ileum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007410:Intestinal Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010539:Permeability / Q000187:drug effects; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054439:Ghrelin; D014409:Tumor Necrosis Factor-alpha