title: Labetalol Prevents Intestinal Dysfunction Induced by Traumatic Brain Injury.
abstract: BACKGROUND
  Beta-adrenergic blockade has been hypothesized to have a protective effect on intestinal dysfunction and increased intestinal permeability associated with the epinephrine surge after traumatic brain injury (TBI).
  
  
  METHODS
  Wister rats were subjected to either a weight drop TBI, and intraperitoneally injected or not with labetalol, or a sham procedure (18 rats per group). After 3, 6, or 12h (6 rats per subgroup), intestinal permeability to 4.4 kDa FITC-Dextran and plasma epinephrine levels were measured as was intestinal tight junction protein ZO-1 expression at 12h. Terminal ileum was harvested to measure levels of intestinal tumor necrosis factor (TNF)-α and to evaluate histopathology.
  
  
  RESULTS
  In TBI group vs. sham group, intestinal permeability (P<0.01) was significantly higher at all time-points, and intestinal ZO-1 expression was lower at 12h. In TBI with vs. without labetalol group, 1) intestinal permeability was significantly lower at 6 and 12h (94.31±7.64 vs. 102.16±6.40 μg/mL; 110.21±7.52 vs. 118.95±7.11 μg/mL, respectively); 2) levels of plasma epinephrine and intestinal TNF-α were significantly lower at 3, 6 and 12h; and 3) intestinal ZO-1 expression was higher at 3, 6 and 12h (p=0.018). Histopathological evaluation showed that labetalol use preserved intestinal architecture throughout.
  
  
  CONCLUSIONS
  In a rat model of TBI, labetalol reduced TBI-induced sympathetic hyperactivity, and prevented histopathological intestinal injury accompanied by changes in gut permeability and gut TNF-α expression.
authors.affiliation: Department of Emergency, Shanghai Fifth Hospital affiliated Fudan University, Shanghai, China.
authors.forename: Yuhuang
authors.initials: Y
authors.lastname: Lang
authors.affiliation: Intensive Care Unit, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Fengming
authors.initials: F
authors.lastname: Fu
authors.affiliation: Department of Gastroenterology, Shanghai Fifth Hospital affiliated Fudan University, Shanghai, China.
authors.forename: Dalong
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Emergency, Shanghai Fifth Hospital affiliated Fudan University, Shanghai, China.
authors.forename: Chenhui
authors.initials: C
authors.lastname: Xi
authors.affiliation: Department of Gastroenterology, Shanghai Fifth Hospital affiliated Fudan University, Shanghai, China.
authors.forename: Fengyuan
authors.initials: F
authors.lastname: Chen
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000473:pathology; D007741:Labetalol / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; C569044:Tjp1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D007741:Labetalol