Gold nanoparticles reduce inflammation in cerebral microvessels of mice with sepsis
Abstract Background Sepsis is an emergency medical condition that can lead to death and it is defined as a life-threatening organ dysfunction caused by immune dysregulation in response to an infection. It is considered the main killer in intensive care units. Sepsis associated-encephalopathy (SAE) i...
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doaj-e98cb7baf0a94dc9b0a00f72a76aff3b2021-02-21T12:07:31ZengBMCJournal of Nanobiotechnology1477-31552021-02-0119111510.1186/s12951-021-00796-6Gold nanoparticles reduce inflammation in cerebral microvessels of mice with sepsisDavide Di Bella0João P. S. Ferreira1Renee de Nazare O. Silva2Cinthya Echem3Aline Milan4Eliana H. Akamine5Maria H. Carvalho6Stephen F. Rodrigues7Laboratory of Hypertension, Diabetes and Vascular Biology, Department of Pharmacology, Institute of Biomedical Sciences, University of Sao PauloLaboratory of Hypertension, Diabetes and Vascular Biology, Department of Pharmacology, Institute of Biomedical Sciences, University of Sao PauloLaboratory of Hypertension, Diabetes and Vascular Biology, Department of Pharmacology, Institute of Biomedical Sciences, University of Sao PauloLaboratory of Hypertension, Diabetes and Vascular Biology, Department of Pharmacology, Institute of Biomedical Sciences, University of Sao PauloLaboratory of Hypertension, Diabetes and Vascular Biology, Department of Pharmacology, Institute of Biomedical Sciences, University of Sao PauloLaboratory of Hypertension, Diabetes and Vascular Biology, Department of Pharmacology, Institute of Biomedical Sciences, University of Sao PauloLaboratory of Hypertension, Diabetes and Vascular Biology, Department of Pharmacology, Institute of Biomedical Sciences, University of Sao PauloLaboratory of Hypertension, Diabetes and Vascular Biology, Department of Pharmacology, Institute of Biomedical Sciences, University of Sao PauloAbstract Background Sepsis is an emergency medical condition that can lead to death and it is defined as a life-threatening organ dysfunction caused by immune dysregulation in response to an infection. It is considered the main killer in intensive care units. Sepsis associated-encephalopathy (SAE) is mostly caused by a sepsis-induced systemic inflammatory response. Studies report SAE in 14–63% of septic patients. Main SAE symptoms are not specific and usually include acute impairment of consciousness, delirium and/or coma, along with electroencephalogram (EEG) changes. For those who recover from sepsis and SAE, impaired cognitive function, mobility and quality of life are often observed months to years after hospital discharge, and there is no treatment available today to prevent that. Inflammation and oxidative stress are key players for the SAE pathophysiology. Gold nanoparticles have been demonstrated to own important anti-inflammatory properties. It was also reported 20 nm citrate-covered gold nanoparticles (cit-AuNP) reduce oxidative stress. In this context, we tested whether 20 nm cit-AuNP could alleviate the acute changes caused by sepsis in brain of mice, with focus on inflammation. Sepsis was induced in female C57BL/6 mice by cecal ligation and puncture (CLP), 20 nm cit-AuNP or saline were intravenously (IV) injected 2 h after induction of sepsis and experiments performed 6 h after induction. Intravital microscopy was used for leukocyte and platelet adhesion study in brain, blood brain barrier (BBB) permeability carried out by Evans blue assay, cytokines measured by ELISA and real time PCR, cell adhesion molecules (CAMs) by flow cytometry and immunohistochemistry, and transcription factors, by western blotting. Results 20 nm cit-AuNP treatment reduced leukocyte and platelet adhesion to cerebral blood vessels, prevented BBB failure, reduced TNF- concentration in brain, and ICAM-1 expression both in circulating polymorphonuclear (PMN) leukocytes and cerebral blood vessels of mice with sepsis. Furthermore, 20 nm cit-AuNP did not interfere with the antibiotic effect on the survival rate of mice with sepsis. Conclusions Cit-AuNP showed important anti-inflammatory properties in the brain of mice with sepsis, being a potential candidate to be used as adjuvant drug along with antibiotics in the treatment of sepsis to avoid SAEhttps://doi.org/10.1186/s12951-021-00796-6Gold nanoparticlesSeptic encephalopathyMiceCell adhesion molecules |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Davide Di Bella João P. S. Ferreira Renee de Nazare O. Silva Cinthya Echem Aline Milan Eliana H. Akamine Maria H. Carvalho Stephen F. Rodrigues |
spellingShingle |
Davide Di Bella João P. S. Ferreira Renee de Nazare O. Silva Cinthya Echem Aline Milan Eliana H. Akamine Maria H. Carvalho Stephen F. Rodrigues Gold nanoparticles reduce inflammation in cerebral microvessels of mice with sepsis Journal of Nanobiotechnology Gold nanoparticles Septic encephalopathy Mice Cell adhesion molecules |
author_facet |
Davide Di Bella João P. S. Ferreira Renee de Nazare O. Silva Cinthya Echem Aline Milan Eliana H. Akamine Maria H. Carvalho Stephen F. Rodrigues |
author_sort |
Davide Di Bella |
title |
Gold nanoparticles reduce inflammation in cerebral microvessels of mice with sepsis |
title_short |
Gold nanoparticles reduce inflammation in cerebral microvessels of mice with sepsis |
title_full |
Gold nanoparticles reduce inflammation in cerebral microvessels of mice with sepsis |
title_fullStr |
Gold nanoparticles reduce inflammation in cerebral microvessels of mice with sepsis |
title_full_unstemmed |
Gold nanoparticles reduce inflammation in cerebral microvessels of mice with sepsis |
title_sort |
gold nanoparticles reduce inflammation in cerebral microvessels of mice with sepsis |
publisher |
BMC |
series |
Journal of Nanobiotechnology |
issn |
1477-3155 |
publishDate |
2021-02-01 |
description |
Abstract Background Sepsis is an emergency medical condition that can lead to death and it is defined as a life-threatening organ dysfunction caused by immune dysregulation in response to an infection. It is considered the main killer in intensive care units. Sepsis associated-encephalopathy (SAE) is mostly caused by a sepsis-induced systemic inflammatory response. Studies report SAE in 14–63% of septic patients. Main SAE symptoms are not specific and usually include acute impairment of consciousness, delirium and/or coma, along with electroencephalogram (EEG) changes. For those who recover from sepsis and SAE, impaired cognitive function, mobility and quality of life are often observed months to years after hospital discharge, and there is no treatment available today to prevent that. Inflammation and oxidative stress are key players for the SAE pathophysiology. Gold nanoparticles have been demonstrated to own important anti-inflammatory properties. It was also reported 20 nm citrate-covered gold nanoparticles (cit-AuNP) reduce oxidative stress. In this context, we tested whether 20 nm cit-AuNP could alleviate the acute changes caused by sepsis in brain of mice, with focus on inflammation. Sepsis was induced in female C57BL/6 mice by cecal ligation and puncture (CLP), 20 nm cit-AuNP or saline were intravenously (IV) injected 2 h after induction of sepsis and experiments performed 6 h after induction. Intravital microscopy was used for leukocyte and platelet adhesion study in brain, blood brain barrier (BBB) permeability carried out by Evans blue assay, cytokines measured by ELISA and real time PCR, cell adhesion molecules (CAMs) by flow cytometry and immunohistochemistry, and transcription factors, by western blotting. Results 20 nm cit-AuNP treatment reduced leukocyte and platelet adhesion to cerebral blood vessels, prevented BBB failure, reduced TNF- concentration in brain, and ICAM-1 expression both in circulating polymorphonuclear (PMN) leukocytes and cerebral blood vessels of mice with sepsis. Furthermore, 20 nm cit-AuNP did not interfere with the antibiotic effect on the survival rate of mice with sepsis. Conclusions Cit-AuNP showed important anti-inflammatory properties in the brain of mice with sepsis, being a potential candidate to be used as adjuvant drug along with antibiotics in the treatment of sepsis to avoid SAE |
topic |
Gold nanoparticles Septic encephalopathy Mice Cell adhesion molecules |
url |
https://doi.org/10.1186/s12951-021-00796-6 |
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