Aging influences in the blood-brain barrier permeability and cerebral oxidative stress in sepsis

Margotti, Willian; Giustina, Amanda Della; Hübner, Marcos; Cidreira, Thainá; Denicol, Taís; Joaquim, Larissa; Carli, Raquel Jaconi De; Danielski, Lucinéia Gainski; Metzker, Kiuanne Lino Lobo; Bonfante, Sandra; Barichello, Tatiana; Petronilho, Fabrícia

doi:10.1016/j.exger.2020.111063

Cited by 15 publications

(7 citation statements)

References 56 publications

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“…As shown in Fig. 2 C, p-STAT3 in macrophages was up-regulated obviously after incubated with IL-6 for 2 h. However, IL-6 induced p-STAT3 in macrophages could be reduced when pretreated with PLGA@M. In addition, myeloperoxidase (MPO) as the biomarker of neutrophils activation was detected in neutrophils under immunofluorescence microscopy [ 49 , 50 ]. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Macrophage biomimetic nanocarriers for anti-inflammation and targeted antiviral treatment in COVID-19

Tan

Meng

et al. 2021

J Nanobiotechnol

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Background The worldwide pandemic of COVID-19 remains a serious public health menace as the lack of efficacious treatments. Cytokine storm syndrome (CSS) characterized with elevated inflammation and multi-organs failure is closely correlated with the bad outcome of COVID-19. Hence, inhibit the process of CSS by controlling excessive inflammation is considered one of the most promising ways for COVID-19 treatment. Results Here, we developed a biomimetic nanocarrier based drug delivery system against COVID-19 via anti-inflammation and antiviral treatment simultaneously. Firstly, lopinavir (LPV) as model antiviral drug was loaded in the polymeric nanoparticles (PLGA-LPV NPs). Afterwards, macrophage membranes were coated on the PLGA-LPV NPs to constitute drugs loaded macrophage biomimetic nanocarriers (PLGA-LPV@M). In the study, PLGA-LPV@M could neutralize multiple proinflammatory cytokines and effectively suppress the activation of macrophages and neutrophils. Furthermore, the formation of NETs induced by COVID-19 patients serum could be reduced by PLGA-LPV@M as well. In a mouse model of coronavirus infection, PLGA-LPV@M exhibited significant targeted ability to inflammation sites, and superior therapeutic efficacy in inflammation alleviation and tissues viral loads reduction. Conclusion Collectively, such macrophage biomimetic nanocarriers based drug delivery system showed favorable anti-inflammation and targeted antiviral effects, which may possess a comprehensive therapeutic value in COVID-19 treatment.

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Section: Resultsmentioning

confidence: 99%

Macrophage biomimetic nanocarriers for anti-inflammation and targeted antiviral treatment in COVID-19

Tan

Meng

et al. 2021

J Nanobiotechnol

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“…There is evidence that age moderates the BBB response to systemic inflammation. Aged male Wistar rats rendered septic by the cecal ligation and perforation procedure demonstrated more profound BBB impairment than younger rats, and this affected both solute (Evans blue) and cellular (neutrophil) influx [ 146 ]. Higher-order interactions between moderators were evident between, for instance, sex and age in mice challenged with intraperitoneal LPS or vehicle; the increase in Evans blue BBB leakage with systemic inflammation was present in males only at a young age but present in both sexes at an older age [ 147 ].…”

Section: Moderators Of the Bbb Responsementioning

confidence: 99%

The blood–brain barrier in systemic infection and inflammation

2021

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The vascular blood–brain barrier is a highly regulated interface between the blood and brain. Its primary function is to protect central neurons while signaling the presence of systemic inflammation and infection to the brain to enable a protective sickness behavior response. With increasing degrees and duration of systemic inflammation, the vascular blood–brain barrier becomes more permeable to solutes, undergoes an increase in lymphocyte trafficking, and is infiltrated by innate immune cells; endothelial cell damage may occasionally occur. Perturbation of neuronal function results in the clinical features of encephalopathy. Here, the molecular and cellular anatomy of the vascular blood–brain barrier is reviewed, first in a healthy context and second in a systemic inflammatory context. Distinct from the molecular and cellular mediators of the blood–brain barrier’s response to inflammation, several moderators influence the direction and magnitude at genetic, system, cellular and molecular levels. These include sex, genetic background, age, pre-existing brain pathology, systemic comorbidity, and gut dysbiosis. Further progress is required to define and measure mediators and moderators of the blood–brain barrier’s response to systemic inflammation in order to explain the heterogeneity observed in animal and human studies.

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“…Recent studies have found that FO enriched lipid emulsion is able to prevent long-term cognitive impairment caused by sepsis, by protecting the BBB as well as inhibiting the activity of MPO ( Della Giustina et al, 2020 ) ( Figure 2 ). Interestingly, Margotti et al found that neutrophils infiltration into brain tissue due to BBB rupture caused an increased production of MPO, accompanied by lipid oxidative damage in the hippocampus and prefrontal cortex, suggesting a vicious circle between BBB destruction and MPO production ( Margotti et al, 2020 ). These results suggested that MPO may become a potential drug target for the treatment of brain dysfunction caused by sepsis ( Margotti et al, 2020 ).…”

Section: Bbb and Saementioning

confidence: 99%

“…Interestingly, Margotti et al found that neutrophils infiltration into brain tissue due to BBB rupture caused an increased production of MPO, accompanied by lipid oxidative damage in the hippocampus and prefrontal cortex, suggesting a vicious circle between BBB destruction and MPO production ( Margotti et al, 2020 ). These results suggested that MPO may become a potential drug target for the treatment of brain dysfunction caused by sepsis ( Margotti et al, 2020 ). Besides, anti-inflammatory and antioxidant drugs, such as metformin, platonin have been shown to exhibit neuroprotective effects, and can improve the decreased expression of TJ proteins induced by sepsis, thereby improving BBB function and attenuating sepsis-induced brain injury ( Yeh et al, 2015 ; Ismail Hassan et al, 2020 ).…”

Section: Bbb and Saementioning

confidence: 99%

Blood-Brain Barrier Disruption by Lipopolysaccharide and Sepsis-Associated Encephalopathy

Peng

Luo

et al. 2021

Front. Cell. Infect. Microbiol.

114

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As a complex multicellular structure of the vascular system at the central nervous system (CNS), the blood-brain barrier (BBB) separates the CNS from the system circulation and regulates the influx and efflux of substances to maintain the steady-state environment of the CNS. Lipopolysaccharide (LPS), the cell wall component of Gram-negative bacteria, can damage the barrier function of BBB and further promote the occurrence and development of sepsis-associated encephalopathy (SAE). Here, we conduct a literature review of the direct and indirect damage mechanisms of LPS to BBB and the relationship between these processes and SAE. We believe that after LPS destroys BBB, a large number of inflammatory factors and neurotoxins will enter and damage the brain tissue, which will activate brain immune cells to mediate inflammatory response and in turn further destroys BBB. This vicious circle will ultimately lead to the progression of SAE. Finally, we present a succinct overview of the treatment of SAE by restoring the BBB barrier function and summarize novel opportunities in controlling the progression of SAE by targeting the BBB.

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Aging influences in the blood-brain barrier permeability and cerebral oxidative stress in sepsis

Cited by 15 publications

References 56 publications

Macrophage biomimetic nanocarriers for anti-inflammation and targeted antiviral treatment in COVID-19

Macrophage biomimetic nanocarriers for anti-inflammation and targeted antiviral treatment in COVID-19

The blood–brain barrier in systemic infection and inflammation

Blood-Brain Barrier Disruption by Lipopolysaccharide and Sepsis-Associated Encephalopathy

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