Donahue Deborah L, Beck Julia, Fritz Braxton, Davis Patrick, Sandoval-Cooper Mayra J, Thomas Scott G, Yount Robert A, Walsh Mark, Ploplis Victoria A, Castellino Francis J
1 W.M. Keck Center for Transgene Research, University of Notre Dame , Notre Dame, Indiana.
J Neurotrauma. 2014 Feb 15;31(4):404-10. doi: 10.1089/neu.2013.3089. Epub 2013 Nov 21.
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.
急性凝血功能障碍是创伤性脑损伤（TBI）的一种严重并发症，由于TBI的复杂性，其病因尚不确定。然而，最近的研究表明，死亡率与早期血小板功能障碍导致的异常止血之间存在关联。本研究的目的是建立并表征一种模拟人类凝血病状态的TBI啮齿动物模型，以便更易于评估TBI早期急性凝血功能障碍的机制。利用大鼠高度可重复的限制性钝性脑损伤进行的研究表明，其与人类TBI患者中观察到的重要损伤后病理变化密切相关，即血小板对激动剂（尤其是二磷酸腺苷（ADP））的反应减弱以及蛛网膜下腔出血。此外，在损伤前给予直接凝血酶抑制剂可恢复血小板对ADP刺激的功能，表明过量凝血酶生成在TBI诱导的早期血小板功能障碍中起直接作用。
