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Effect of gold nanoparticles treatment on the acute expression of inflammatory transcription factors and on the chronic expression of excitatory neurotransmiters in brain of sepsis encephalophaty-induced mice

Grant number: 18/12258-6
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2018
Effective date (End): April 30, 2019
Field of knowledge:Biological Sciences - Pharmacology
Principal researcher:Stephen Fernandes de Paula Rodrigues
Grantee:João Paulo de Sousa Ferreira
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:14/05146-6 - Therapeutical efficacy of gold nanoparticles to glioblastoma multiform or septic encephalopathy in mice, AP.JP

Abstract

Sepsis is a disease that occurs after an exaggerated response against a germ takes place into the host. Several organs, such as lungs, liver, kidneys, blood vessels, and central nervous system (CNS), are affected; consequently, that disease can be fatal. Sepsis acutely acting on the CNS can cause encephalopathy. Some studies have showed that the number of people with sepsis encephalopathy may reach 71% of those with diagnosis of sepsis. Sepsis shock happens when patients' blood pressure dramatically falls after sepsis, which is followed by low organ perfusion and failure. For those who survive sepsis, 13 to 21% may have some cognitive impairment and there is no available treatment to prevent that brain failure. As important contributors for sepsis-induced encephalopathy are inflammation and oxidative stress. In this regard, we have demonstrated citrate-conjugated gold nanoparticles (cit-AuNPs), 20 nm in average diameter, reduces inflammation and oxidative stress, abrogates leukocyte and platelets adhesion to pial vessels, and diminishes parameters indicative of anxiety behavior in mice with sepsis; however, mechanisms governing those effects are still missing. Then, we aimed to study the effect of 20 nm diameter cit-AuNPs acute treatment on the inflammatory transcription factors expression, and on the excitatory neurotransmitors expression in the brain of mice with sepsis. In order to do that, sepsis will be induced in 8-to-12-week-old C57Bl/6 female mice using a cecal ligation and perforation model. Two hours later, 1.9x10 to the power of eleven cit-AuNPs (20 nm diameter and zeta potential equal to -26.1 mV), or saline (control) will be intravenously injected. Six hours after, mice will be euthanized and brain will be collected and frozen (- 80oC) for further use. Protein expression for the following inflammation related-transcription factors molecules: AP-1, HIF-1alpha, IkBalpha, and phosphorylated IkBalpha, will be measured by western blotting. An additional group of animals treated 6 and 24 h after sepsis with cit-AuNPs or saline will have their brain collected 30 days after sepsis induction (at this point, animals no longer have sepsis symptoms) and frozen, as mentioned above. Then the following neurotransmitters will be measured into the brain cortex, hippocampi, and striatum: serotonin, dopamine, and noradrenaline, by ELISA.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DI BELLA, DAVIDE; FERREIRA, JOAO P. S.; SILVA, RENEE DE NAZARE O.; ECHEM, CINTHYA; MILAN, ALINE; AKAMINE, ELIANA H.; CARVALHO, MARIA H.; RODRIGUES, STEPHEN F. Gold nanoparticles reduce inflammation in cerebral microvessels of mice with sepsis. JOURNAL OF NANOBIOTECHNOLOGY, v. 19, n. 1 FEB 19 2021. Web of Science Citations: 1.

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