title: Early platelet dysfunction in a rodent model of blunt traumatic brain injury reflects the acute traumatic coagulopathy found in humans.
abstract: Acute coagulopathy is a serious complication of traumatic brain injury (TBI) and is of uncertain etiology because of the complex nature of TBI. However, recent work has shown a correlation between mortality and abnormal hemostasis resulting from early platelet dysfunction. The aim of the current study was to develop and characterize a rodent model of TBI that mimics the human coagulopathic condition so that mechanisms of the early acute coagulopathy in TBI can be more readily assessed. Studies utilizing a highly reproducible constrained blunt-force brain injury in rats demonstrate a strong correlation with important postinjury pathological changes that are observed in human TBI patients, namely, diminished platelet responses to agonists, especially adenosine diphosphate (ADP), and subarachnoid bleeding. Additionally, administration of a direct thrombin inhibitor, preinjury, recovers platelet functionality to ADP stimulation, indicating a direct role for excess thrombin production in TBI-induced early platelet dysfunction.
authors.affiliation: 1 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.forename: Julia
authors.initials: J
authors.lastname: Beck
authors.forename: Braxton
authors.initials: B
authors.lastname: Fritz
authors.forename: Patrick
authors.initials: P
authors.lastname: Davis
authors.forename: Mayra J
authors.initials: MJ
authors.lastname: Sandoval-Cooper
authors.forename: Scott G
authors.initials: SG
authors.lastname: Thomas
authors.forename: Robert A
authors.initials: RA
authors.lastname: Yount
authors.forename: Mark
authors.initials: M
authors.lastname: Walsh
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Ploplis
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Castellino
mesh_terms: D000208:Acute Disease; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001772:Blood Cell Count; D001778:Blood Coagulation Disorders / Q000097:blood* / Q000209:etiology / Q000473:pathology; D001792:Blood Platelets / Q000187:drug effects*; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000097:blood* / Q000150:complications / Q000473:pathology; D006629:Hirudins / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000502:physiology; D011516:Prothrombin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013345:Subarachnoid Hemorrhage / Q000097:blood; D013916:Thrombelastography; D013917:Thrombin / Q000037:antagonists & inhibitors; D014949:Wounds, Nonpenetrating / Q000097:blood* / Q000473:pathology
chemical_list: D006629:Hirudins; D011994:Recombinant Proteins; D000244:Adenosine Diphosphate; D011516:Prothrombin; D013917:Thrombin; C083544:lepirudin
references.citation: J Emerg Med. 2010 Oct;39(4):399-405
references.pmid: 18584993
references.citation: Am J Med. 1980 Aug;69(2):235-40
references.pmid: 7405945
references.citation: J Trauma Acute Care Surg. 2013 May;74(5):1252-9
references.pmid: 23609275
references.citation: J Neurotrauma. 2008 Aug;25(8):997-1001
references.pmid: 18687038
references.citation: Neurol India. 2005 Jun;53(2):178-82
references.pmid: 16010055
references.citation: Pharmacol Rep. 2008 Jan-Feb;60(1):3-11
references.pmid: 18276980
references.citation: J Trauma Acute Care Surg. 2012 Jul;73(1):13-9
references.pmid: 22743367
references.citation: Rehabil Res Pract. 2012;2012:659652
references.pmid: 22848836
references.citation: MMWR Surveill Summ. 2011 May 6;60(5):1-32
references.pmid: 21544045
references.citation: J Trauma. 2001 Oct;51(4):639-47
references.pmid: 11586152
references.citation: Thromb Haemost. 2009 Aug;102(2):248-57
references.pmid: 19652875
references.citation: Transfusion. 2013 Jan;53 Suppl 1:28S-37S
references.pmid: 23301970
references.citation: J Neurotrauma. 2007 Nov;24(11):1699-706
references.pmid: 18001200
references.citation: Proc Natl Acad Sci U S A. 1979 Jan;76(1):121-5
references.pmid: 218191
references.citation: J Trauma. 2009 Jan;66(1):55-61; discussion 61-2
references.pmid: 19131806
references.citation: J Clin Invest. 2001 Jun;107(12):1503-5
references.pmid: 11413156
references.citation: J Trauma. 2008 Oct;65(4):748-54
references.pmid: 18849786
references.citation: Neurocrit Care. 2013 Apr;18(2):201-8
references.pmid: 22847397
references.citation: Am J Surg. 2012 May;203(5):584-588
references.pmid: 22425448
references.citation: J Am Coll Surg. 2012 May;214(5):739-46
references.pmid: 22520693
references.citation: Thromb Res. 2012 May;129(5):551-6
references.pmid: 22197179
references.citation: Neurocrit Care. 2010 Apr;12(2):211-9
references.pmid: 19806475
references.citation: Crit Care Med. 1998 Jan;26(1):149-56
references.pmid: 9428558
references.citation: NeuroRx. 2005 Jul;2(3):410-22
references.pmid: 16389305
references.citation: J Neurosurg. 1973 Aug;39(2):178-80
references.pmid: 4719695
references.citation: J Trauma. 2002 Jun;52(6):1071-7; discussion 1077
references.pmid: 12045632