Death receptor (DR) signaling has a major impact on the outcome of numerous neurological diseases, including ischemic stroke. DRs mediate not only cell death signals, but also proinflammatory responses and cell proliferation. Identification of regulatory proteins that control the switch between apoptotic and alternative DR signaling opens new therapeutic opportunities. Fas apoptotic inhibitory molecule 2 (Faim2) is an evolutionary conserved, neuron-specific inhibitor of Fas/CD95-mediated apoptosis. To investigate its role during development and in disease models, we generated Faim2-deficient mice. The ubiquitous null mutation displayed a viable and fertile phenotype without overt deficiencies. However, lack of Faim2 caused an increase in susceptibility to combined oxygen-glucose deprivation in primary neurons in vitro as well as in caspase-associated cell death, stroke volume, and neurological impairment after cerebral ischemia in vivo. These processes were rescued by lentiviral Faim2 gene transfer. In summary, we provide evidence that Faim2 is a novel neuroprotective molecule in the context of cerebral ischemia.
BackgroundHyperfibrinolysis (HF) is a major contributor to coagulopathy and mortality in trauma patients. This study investigated (i) the rate of HF during the pre-hospital management of patients with multiple injuries and (ii) the effects of pre-hospital tranexamic acid (TxA) administration on the coagulation system.MethodsFrom 27 trauma patients with pre-hospital an estimated injury severity score (ISS) ≥16 points blood was obtained at the scene and on admission to the emergency department (ED). All patients received 1 g of TxA after the first blood sample was taken. Rotational thrombelastometry (ROTEM) was performed for both blood samples, and the results were compared. HF was defined as a maximum lysis (ML) >15 % in EXTEM.ResultsThe median (min-max) ISS was 17 points (4–50 points). Four patients (15 %) had HF diagnosed via ROTEM at the scene, and 2 patients (7.5 %) had HF diagnosed via ROTEM on admission to the ED. The median ML before TxA administration was 11 % (3–99 %) vs. 10 % after TxA administration (4–18 %; p > 0.05). TxA was administered 37 min (10–85 min) before ED arrival. The ROTEM results before and after TxA administration did not significantly differ. No adverse drug reactions were observed after TxA administration.DiscussionHF can be present in severely injured patients during pre-hospital care. Antifibrinolytic therapy administered at the scene is a significant time saver. Even in milder trauma fibrinogen can be decreased to critically low levels. Early administration of TxA cannot reverse or entirely stop this decrease.ConclusionsThe pre-hospital use of TxA should be considered for severely injured patients to prevent the worsening of trauma-induced coagulopathy and unnecessarily high fibrinogen consumption.Trial registrationClinicalTrials.gov ID NCT01938768 (Registered 5 September 2013).
The implementation of an accurate and patient status-based alarm system to mobilize the trauma team can improve the quality of treatment while the duration of treatment of the severely injured patients in the TRU can be decreased. It also provides a most efficient mobilization of personnel resources while sustaining patient safety.
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