title: The role of microglia activation in the development of sepsis-induced long-term cognitive impairment.
abstract: Oxidative stress and inflammation is likely to be a major step in the development of sepsis-associated encephalopathy (SAE) and long-term cognitive impairment. To date, it is not known whether brain inflammation and oxidative damage are a direct consequence of systemic inflammation or whether these events are driven by brain resident cells, such as microglia. Therefore, the aim of this study is to evaluate the effect of minocycline on behavioral and neuroinflammatory parameters in rats submitted to sepsis. Male Wistar rats were subjected to sepsis by cecal ligation and puncture (CLP). The animals were divided into sham-operated (Sham+control), sham-operated plus minocycline (sham+MIN), CLP (CLP+control) and CLP plus minocycline (CLP+MIN) (100 μg/kg, administered as a single intracerebroventricular (ICV) injection). Some animals were killed 24h after surgery to assess the breakdown of the blood brain barrier, cytokine levels, oxidative damage to lipids (TBARS) and proteins in the hippocampus. Some animals were allowed to recover for 10 days when step-down inhibitory avoidance and open-field tasks were performed. Treatment with minocycline prevented an increase in markers of oxidative damage and inflammation in the hippocampus after sepsis. This was associated with an improvement in long-term cognitive performance. In conclusion, we demonstrated that the inhibition of the microglia by an ICV injection of minocycline was able to decrease acute brain oxidative damage and inflammation as well as long-term cognitive impairment in sepsis survivors.
authors.affiliation: Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, 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: Andriele S
authors.initials: AS
authors.lastname: Vieira
authors.affiliation: Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Francieli
authors.initials: F
authors.lastname: Vuolo
authors.affiliation: Laboratory of Inborn Errors of Metabolism, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Hugo Galvane
authors.initials: HG
authors.lastname: Zapelini
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: Mendonça
authors.affiliation: Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Francielle
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: Diogo
authors.initials: D
authors.lastname: Dominguini
authors.affiliation: Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil; Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Amanda
authors.initials: A
authors.lastname: Steckert
authors.affiliation: Laboratory of Inborn Errors of Metabolism, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil.
authors.forename: Patrícia Fernanda
authors.initials: PF
authors.lastname: Schuck
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, USA.
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.affiliation: Laboratory of Clinical and Experimental Pathophysiology, Graduate Program in Health Sciences, University of South of Santa Catarina, Tubarão, 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, USA.
authors.forename: Fabrícia
authors.initials: F
authors.lastname: Petronilho
authors.affiliation: Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil. Electronic address: fdpizzol@gmail.com.
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D003072:Cognition Disorders / Q000209:etiology* / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D006624:Hippocampus / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000150:complications* / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D016207:Cytokines; D017392:Thiobarbituric Acid Reactive Substances
keywords: Blood brain-barrier; Encephalopathy; Microglia; Minocycline; Sepsis