Assessing a Novel Adaptation to CCI Devices to Model Human Mild Traumatic Brain Injury

Background: Traumatic Brain Injuries (TBIs) are a health crisis with over a million people suffering injuries each year in the United States. The majority of TBIs are mild injuries which often produce no period of unconsciousness and no gross damage to the brain or skull. A range of TBI animal models exist but many produce injuries too severe to characterize as mild. One TBI induction method commonly used is Controlled Cortical Impact (CCI) devices. New Method: The purpose of this study is to assess a novel adaptation to CCI devices that allows for the induction of mild injuries that mimic human mild TBI (mTBI). In this apparatus, the mouse is placed on an elevated platform which utilizes a sensor to collapse the platform as the impactor hits the head. Results: On the first day of injury, the repetitive dropping platform group had a significantly lower Time to Righting (TTR) than both control and single hit stationary platform groups. Additionally, on the first day of injury the single-hit stationary group had a significantly increased Time to Ambulation (TTA) compared to all other groups. Furthermore, this adaptation produces significantly less GFAP than CCI injuries performed without the falling platform. Comparison with existing models: This model incorporates the high control of the CCI device that may be lost in weight-drop models of mild injury while also producing translational mild injuries. Conclusion: This adaptation can be used in any CCI research lab to translationally study mild injuries. This will facilitate murine research into mTBI

Coagulopathy as a result of factor V inhibitor after exposure to bovine topical thrombin

AbstractWe describe a case of severe coagulopathy after mesenteric revascularization. Laboratory investigation results revealed the presence of plasma inhibitors of factor V believed to result from exposure to bovine thrombin used for intraoperative hemostasis. Vascular and cardiothoracic surgeons commonly use topical thrombin for surgical hemostasis, and many patients undergo multiple exposure. More patients likely have factor V inhibitors develop than has previously been realized, and this may account for some otherwise unexplained postoperative coagulation disorders. This report may alert surgeons to coagulation disturbances that can result from exposure to bovine thrombin and provide guidelines for diagnosis and management. (J Vasc Surg 2002;35:400-2.

Progressive intermittent claudication is associated with impaired fibrinolysis

AbstractPurpose: Acute complications of atherosclerosis such as stroke and myocardial infarction are caused by thrombosis and may be associated with impaired fibrinolytic activity. The current study was performed to determine whether peripheral arterial disease (PAD) and its progression are also associated with impaired fibrinolysis, by measurement of tissue plasminogen activator (tPA, the activator of fibrinolysis) and its inhibitor plasminogen activator inhibitor-1 (PAI-1). Methods: The study group consisted of 80 men with a mean age of 69 years. This included 18 patients with mild intermittent claudication (MC, pain-free walking distance ≥200 meters) and 51 patients with severe claudication (SC, walking distance <200 meters). Eleven age- and sex-matched patients without PAD served as controls. All patients had measurements of serum tPA antigen using an enzyme-linked immunoadsorbent assay. Serum levels of tPA and PAI-1 activity were assayed with an amidolytic method. Mean ± SEM levels of the enzyme levels in patients with progressively more severe PAD were compared with normal controls. Results: Serum PAI-1 activity levels were significantly elevated in both PAD groups compared with normal controls (p < 0.02). There were no significant differences in the PAI-1 activity levels in groups with worsening degrees of PAD. There was a significant decrease in tPA activity levels in patients with SC (p = 0.01) relative to those with MC and the normal subjects. There was also a significant increase in tPA antigen level in the patients with SC compared with those with MC and the control subjects, as well as a significant inverse correlation between tPA antigen levels and pain-free walking time in patients with claudication (p = 0.001). Conclusions: All patients with PAD in this study had significant reductions in endogenous fibrinolytic activity. Patients with SC had more impaired fibrinolytic activity than those with MC and the control subjects, suggesting that the progression to more severe levels of PAD may be associated with worsening endogenous fibrinolysis. (J Vasc Surg 1998;27:645-50.