title: The role of neuropeptide Y and aquaporin 4 in the pathogenesis of intestinal dysfunction caused by traumatic brain injury.
abstract: BACKGROUND
  Although the exact incidence is unknown, traumatic brain injury (TBI) can lead to intestinal dysfunction. It has important influence on the early nutrition and prognosis of TBI patients. Experiments were designed to study the roles of neuropeptide Y (NPY) and aquaporin 4 (AQP4) in the pathogenesis of intestinal dysfunction caused by TBI and to find some new solutions for the treatment of intestinal dysfunction after TBI.
  
  
  METHODS
  Forty adult male Wistar rats were randomly divided into control, mild trauma, moderate trauma, and severe trauma groups. TBI was induced by Feeney's impact method. Control animals were sham operated but not subjected to the impact test. All rats were killed 24 h after surgery. Blood samples were obtained from the abdominal aorta for enzyme-linked immunosorbent assay measurement of NPY concentrations. Jejunum segments 15 cm distal to the Treitz ligament were taken for analysis of NPY and AQP4 expression by polymerase chain reaction, Western blot, and immunohistochemistry. Pathologic changes in intestinal cell structure and ultrastructure were studied by light microscopy and transmission electron microscopy.
  
  
  RESULTS
  The specimens from different groups showed different degrees of structural changes, ranging from swelling and degeneration of villous epithelial cells to extensive denudation and collapse of the villi. The more severe the trauma, the more serious the degree of intestinal mucosal injury. Intestinal smooth muscle also showed varying degrees of edema and structural disorder. Electron microscopy showed that intestinal mitochondria had varying degrees of swelling and the structure of mitochondrial crista was disordered and even fractured. Plasma concentrations of NPY and jejunal gene and protein expressions of NPY and AQP4 increased significantly following TBI (P < 0.05), with greater increases at higher levels of injury. Moreover, there were positive correlations between NPY and AQP4 (P < 0.05).
  
  
  CONCLUSIONS
  Increasing grades of TBI caused increasing degrees of intestinal ischemia and edema, and thus caused increasingly severe intestinal dysfunction. AQP4 and NPY may be involved in the pathogenesis of intestinal dysfunction after TBI. Increased NPY levels may be responsible for intestinal ischemia and hypoxia, and AQP4 may play an important role in intestinal edema. Increased NPY levels may be one of the main causes for the increase in AQP4 after TBI.
authors.affiliation: Department of Neurosurgery, First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi Province, China.
authors.forename: Hubin
authors.initials: H
authors.lastname: Duan
authors.forename: Chunyan
authors.initials: C
authors.lastname: Hao
authors.forename: Yimin
authors.initials: Y
authors.lastname: Fan
authors.forename: Hongqin
authors.initials: H
authors.lastname: Wang
authors.forename: Yueting
authors.initials: Y
authors.lastname: Liu
authors.forename: Jiehe
authors.initials: J
authors.lastname: Hao
authors.forename: Cuiping
authors.initials: C
authors.lastname: Xu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Liu
authors.forename: Huaping
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D001930:Brain Injuries / Q000150:complications* / Q000503:physiopathology*; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D007422:Intestines / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D007583:Jejunum / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D009478:Neuropeptide Y / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index
chemical_list: D051401:Aquaporin 4; D015415:Biomarkers; D009478:Neuropeptide Y; D012333:RNA, Messenger
keywords: Aquaporin 4; Brain injury; Intestinal dysfunction; Neuropeptide Y; Pathogenesis