title: Protective effects of urinary trypsin inhibitor on vascular permeability following subarachnoid hemorrhage in a rat model.
abstract: OBJECTIVE
  Inflammation and apoptosis play important roles in increasing vascular permeability following subarachnoid hemorrhage (SAH). The objective of this study was to evaluate whether urinary trypsin inhibitor (UTI), a serine protease inhibitor, attenuates vascular permeability by its antiinflammatory and antiapoptotic effects after experimental SAH.
  
  
  METHODS
  Subarachnoid hemorrhage models were established in adult male Sprague-Dawley rats by endovascular perforation. UTI was administered by intraperitoneal injection immediately following SAH. Brain edema was assessed by magnetic resonance imaging (MRI) at 24 h after SAH. Neurological deficits, brain water content, vascular permeability, malondialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity were evaluated. Immunohistochemical staining and Western blot were used to explore the underlying protective mechanism of UTI.
  
  
  RESULTS
  Urinary trypsin inhibitor 50,000 U/kg significantly attenuated brain edema and neurological deficits and reduced vascular permeability at 24 h after SAH. MDA concentration and MPO activity in hippocampus were significantly decreased with UTI treatment. Furthermore, the levels of phosphorylated JNK, NF-κB (p65), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and proapoptotic protein p53, caspase-3 were elevated in the microvascular endothelial cells of the hippocampus after SAH, which were alleviated with UTI treatment.
  
  
  CONCLUSIONS
  Urinary trypsin inhibitor reduced vascular permeability after SAH through its antiinflammatory and antiapptotic effects via blocking the activity of JNK, NF-κB, and p53.
authors.affiliation: Department of Intensive Care Unit, Jishuitan Hospital, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhou
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.forename: Ying
authors.initials: Y
authors.lastname: Bai
authors.forename: Sherchan
authors.initials: S
authors.lastname: Prativa
authors.forename: Jia-Zhou
authors.initials: JZ
authors.lastname: Xu
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Han
authors.forename: Jun-Hao
authors.initials: JH
authors.lastname: Yan
mesh_terms: D000818:Animals; D002199:Capillary Permeability; D004195:Disease Models, Animal; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D016328:NF-kappa B / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D014361:Trypsin Inhibitors / Q000502:physiology* / Q000652:urine
chemical_list: D016328:NF-kappa B; D014361:Trypsin Inhibitors; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Magnetic resonance imaging; Rat; Subarachnoid hemorrhage; Urinary trypsin inhibitor; Vascular permeability