The story of an exceptional serine protease, tissue-type plasminogen activator (tPA).

The only acute treatment of ischemic stroke approved by the health authorities is tissue recombinant plasminogen activator (tPA)-induced thrombolysis. Under physiological conditions, tPA, belonging to the serine protease family, is secreted by endothelial and brain cells (neurons, astrocytes, microglia, oligodendrocytes). Although revascularisation induced by tPA is beneficial during a stroke, research over the past 20 years shows that tPA can also be deleterious for the brain parenchyma. Thus, in this review of the literature, after a brief history on the discovery of tPA, we reviewed current knowledge of mechanisms by which tPA can influence brain function in physiological and pathological conditions.

Assessment of general emergency medicine physicians' medical education regarding management of pediatric emergencies in western Normandy, France.

OBJECTIVES: General emergency medicine physicians sometimes have to deal with acute management of pediatric emergencies. The objectives of this study were to assess the pediatric medical education background of emergency physicians, how often they encounter pediatric emergencies, as well as the knowledge and organizational gaps regarding the management of children in general emergency departments. METHODS: A survey was conducted from March 25 to June 25, 2017, by emailing an anonymized questionnaire to all senior emergency physicians of the 22 general emergency departments of western Normandy public hospitals. RESULTS: A total of 81 responses were analyzed. In all, 83% percent of respondents had previously worked in a pediatric department. In total, 90% of the respondents reported caring for children within their emergency department and 93% out-of-hospital (100% of them during primary interventions and 39% during secondary interventions such as inter-hospital transfers). Fourteen percent of the respondents considered that the pediatric medical education they received was adapted to their current practice, while 73% reported experiencing difficulties during management of pediatric emergencies (technical difficulties, unsuitable material and therapeutics, relational problems, personal apprehension, disease- or age-specific difficulties, especially with children under the age of 2-3 years). CONCLUSION: Most general emergency physicians report caring for children despite a lack of medical education in pediatrics. Pediatric medical education as well as collaborations between general practitioners and specialized pediatric teams should be enhanced to better match the needs of general emergency departments and improve the quality of primary and acute care for children.

Unveiling an exceptional zymogen: the single-chain form of tPA is a selective activator of NMDA receptor-dependent signaling and neurotoxicity.

Unlike other serine proteases that are zymogens, the single-chain form of tissue plasminogen activator (sc-tPA) exhibits an intrinsic activity similar to that of its cleaved two-chain form (tc-tPA), especially in the presence of fibrin. In the central nervous system tPA controls brain functions and dysfunctions through its proteolytic activity. We demonstrated here, both in vitro and in vivo, that the intrinsic activity of sc-tPA selectively modulates N-methyl-D-aspartate receptor (NMDAR) signaling as compared with tc-tPA. Thus, sc-tPA enhances NMDAR-mediated calcium influx, Erk(½) activation and neurotoxicity in cultured cortical neurons, excitotoxicity in the striatum and NMDAR-dependent long-term potentiation in the hippocampal CA-1 network. As the first demonstration of a differential function for sc-tPA and tc-tPA, this finding opens a new area of investigations on tPA functions in the absence of its allosteric regulator, fibrin.