Presenting Author: Lucille ADAM
, Scientist at Univ. Paris Saclay, Univ. Paris Saclay
Abstract:
Sepsis via innate immune system activation causes organ dysfunction. Among these, the central nervous system (CNS) is particularly affected by sepsis-associated encephalopathies. These symptoms are linked with the activation of microglia and leukocyte infiltration. These immune cells have been discovered to have the ability to produce extracellular traps (ETs). While these components capture and destroy pathogens, deleterious effects occur such as reduced neuronal excitability with excessive production. In this study, the objectives were to determine whether (1) immune cells form ETs in the CNS by using two models of sepsis: lipopolysaccharide (LPS) and cecal ligation and puncture (CLP); (2) ETs produce neuromuscular disorders, and (3) a threshold is necessary to produce these disorders. Our results demonstrate a systemic inflammation for both models. As expected, the LPS administration increases leukocyte infiltration into the CNS, activates immune cells and produces ETs, which directly impair the gastrocnemius motoneuron excitability. Sivelastat, an inhibitor of ET formation significantly decreases the production of ETs in immune cells and induces a preservation of the neuromuscular function without decrease of the inflammatory response. This infiltration of leukocytes and production of ETs is also observed using the CLP model, at a lower stage, without neuromuscular dysfunctions, suggesting that the CNS has an ET threshold in order to display these deleterious effects.
Modulation of neuromuscular function through extracellular traps in septic shock models
Category
Poster and Podium (Block Symposium)
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Date: May 4 Presentation Time: 11:30 AM to 12:45 PM Room: Exhibit Hall F1