title: CD40-CD40 Ligand Pathway is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis.
abstract: Sepsis-associated encephalopathy (SAE) is associated with an increased rate of morbidity and mortality. It is not understood what the exact mechanism is for the brain dysfunction that occurs in septic patients, but brain inflammation and oxidative stress are a possible theory. Such events can occur through the alteration of molecules that perpetuate the inflammatory response. Thus, it is possible to postulate that CD40 may be involved in this process. The aim of this work is to evaluate the role of CD40-CD40L pathway activation in brain dysfunction associated with sepsis in an animal model. Microglia activation induces the upregulation of CD40-CD40L, both in vitro and in vivo. The inhibition of microglia activation decreases levels of CD40-CD40L in the brain and decreases brain inflammation, oxidative damage and blood brain barrier dysfunction. Despite this, anti-CD40 treatment does not improve mortality in this model. However, it is able to improve long-term cognitive impairment in sepsis survivors. In conclusion, there is a major involvement of the CD40-CD40L signaling pathway in long-term brain dysfunction in an animal model of sepsis.
authors.affiliation: Laboratory of Clinical and Experimental Pathophysiology, Graduate Program in Health Sciences, University of South of Santa Catarina, Tubarão, SC, Brazil.
authors.forename: Monique
authors.initials: M
authors.lastname: Michels
authors.affiliation: Laboratory of Clinical and Experimental Pathophysiology, Graduate Program in Health Sciences, University of South of Santa Catarina, Tubarão, SC, Brazil.
authors.forename: Lucinéia Gainski
authors.initials: LG
authors.lastname: Danieslki
authors.affiliation: Laboratory of Clinical and Experimental Pathophysiology, Graduate Program in Health Sciences, University of South of Santa Catarina, Tubarão, SC, Brazil.
authors.forename: Andriele
authors.initials: A
authors.lastname: Vieira
authors.affiliation: Laboratory of Clinical and Experimental Pathophysiology, Graduate Program in Health Sciences, University of South of Santa Catarina, Tubarão, SC, Brazil.
authors.forename: Drielly
authors.initials: D
authors.lastname: Florentino
authors.affiliation: Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Dhébora
authors.initials: D
authors.lastname: Dall'Igna
authors.affiliation: Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Letícia
authors.initials: L
authors.lastname: Galant
authors.affiliation: Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sonai
authors.affiliation: Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Francieli
authors.initials: F
authors.lastname: Vuolo
authors.affiliation: Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Franciele
authors.initials: F
authors.lastname: Mina
authors.affiliation: Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Pescador
authors.affiliation: Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Diogo
authors.initials: D
authors.lastname: Dominguini
authors.affiliation: Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.|Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States of America.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Barichello
authors.affiliation: Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.|Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States of America.
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.affiliation: Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
authors.affiliation: Laboratory of Clinical and Experimental Pathophysiology, Graduate Program in Health Sciences, University of South of Santa Catarina, Tubarão, SC, Brazil.
authors.forename: Fabrícia
authors.initials: F
authors.lastname: Petronilho
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015415:Biomarkers; D001812:Blood-Brain Barrier / Q000378:metabolism; D019013:CD40 Antigens / Q000037:antagonists & inhibitors / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D017628:Microglia / Q000378:metabolism; D018805:Sepsis / Q000150:complications* / Q000378:metabolism* / Q000401:mortality; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D019013:CD40 Antigens; D023201:CD40 Ligand
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