title: Early coagulation events induce acute lung injury in a rat model of blunt traumatic brain injury.
abstract: Acute lung injury (ALI) and systemic coagulopathy are serious complications of traumatic brain injury (TBI) that frequently lead to poor clinical outcomes. Although the release of tissue factor (TF), a potent initiator of the extrinsic pathway of coagulation, from the injured brain is thought to play a key role in coagulopathy after TBI, its function in ALI following TBI remains unclear. In this study, we investigated whether the systemic appearance of TF correlated with the ensuing coagulopathy that follows TBI in ALI using an anesthetized rat blunt trauma TBI model. Blood and lung samples were obtained after TBI. Compared with controls, pulmonary edema and increased pulmonary permeability were observed as early as 5 min after TBI without evidence of norepinephrine involvement. Systemic TF increased at 5 min and then diminished 60 min after TBI. Lung injury and alveolar hemorrhaging were also observed as early as 5 min after TBI. A biphasic elevation of TF was observed in the lungs after TBI, and TF-positive microparticles (MPs) were detected in the alveolar spaces. Fibrin(ogen) deposition was also observed in the lungs within 60 min after TBI. Additionally, preadministration of a direct thrombin inhibitor, Refludan, attenuated lung injuries, thus implicating thrombin as a direct participant in ALI after TBI. The results from this study demonstrated that enhanced systemic TF may be an initiator of coagulation activation that contributes to ALI after TBI.
authors.affiliation: W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana;
authors.forename: Hideki
authors.initials: H
authors.lastname: Yasui
authors.affiliation: W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana;
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Donahue
authors.affiliation: W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana; Memorial Hospital of South Bend, South Bend, Indiana.
authors.forename: Mark
authors.initials: M
authors.lastname: Walsh
authors.affiliation: W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana; and.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Castellino
authors.affiliation: W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana; and vploplis@nd.edu.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Ploplis
mesh_terms: D055371:Acute Lung Injury / Q000097:blood* / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D000991:Antithrombins / Q000494:pharmacology; D001777:Blood Coagulation; D000070642:Brain Injuries, Traumatic / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006629:Hirudins / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000502:physiology; D008297:Male; D010974:Platelet Aggregation; D010976:Platelet Count; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D000991:Antithrombins; C000614142:Gfap protein, rat; D005904:Glial Fibrillary Acidic Protein; D006629:Hirudins; D011994:Recombinant Proteins; C083544:lepirudin
keywords: acute lung injury; coagulation pathway; coagulopathy; tissue factor; traumatic brain injury