Correlation of Acute Phase Inflammatory and Oxidative Markers With Long-term Cognitive Impairment in Sepsis Survivors Rats

Biff, Daiane; Petronilho, Fabrícia; Constantino, Larissa; Vuolo, Francieli; Zamora-Berridi, Grettel J.; Dall'Igna, Dhébora Mozena; Comim, Clarissa M.; Quevedo, Joao L De; Kapczinski, Flávio; Dal‐Pizzol, Felipe

doi:10.1097/shk.0b013e3182959cfa

Cited by 35 publications

(12 citation statements)

References 28 publications

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“…We demonstrated that septic animals presented low levels of BDNF in hippocampus 48 h after induction. Recently, our group showed that the maintenance of brain inflammation at early stages of sepsis development was associated with lower levels of BDNF in the hippocampus and worse performance in the inhibitory avoidance task 30 days after sepsis (Biff et al, 2013). It is well known that both acute and chronic stress can decrease the brain levels of BDNF (Kaplan et al, 2010); thus, it seems that sepsis-induced brain inflammation can be associated with lower brain levels of BDNF and consequent CNS dysfunction.…”

Section: Discussionmentioning

confidence: 98%

Evaluation of NCS-1, DARPP-32, and neurotrophins in hippocampus and prefrontal cortex in rats submitted to sepsis

Comim

Silva

Mina

et al. 2014

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Sepsis is defined as the host's reaction to infection and it is characterized by a systemic inflammatory response with important clinical implications. Central nervous system dysfunction secondary to sepsis is associated with local generation of pro- and anti-inflammatory cytokines, impaired cerebral microcirculation, disturbance of neurotransmitters, apoptosis, and cognitive impairment. It is known that during the process of learning and memory formation several pathways are involved such as dopaminergic and cholinergic systems. Thus, the objective of this study is to evaluate the neuronal calcium sensor (NCS-1) and dopamine-cAMP regulated phosphoprotein of 32,000 kDa (DARPP-32) expression as well as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in prefrontal cortex and hippocampus of rats 12, 24, and 48 h after sepsis induction. To this aim, we used sham-operated Wistar rats or submitted to the cecal ligation and perforation procedure. After 12 and 24 h, there was an increase of NGF levels in hippocampus; and up to 48 h, a decrease of NCS-1 expression in prefrontal cortex, a decrease of BDNF levels in hippocampus and an increase of NGF levels in hippocampus. In conclusion, we believe that the low expression of NCS-1 in prefrontal cortex and low levels of BDNF in hippocampus may be associated with the pathophysiology of cognitive impairment during sepsis and a putative role of the dopaminergic system.

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Section: Discussionmentioning

confidence: 98%

Evaluation of NCS-1, DARPP-32, and neurotrophins in hippocampus and prefrontal cortex in rats submitted to sepsis

Comim

Silva

Mina

et al. 2014

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“…We extensively characterized acute and long-term cognitive impairment and brain inflammation using this animal model. 3,[17][18][19]…”

Section: Sepsis Induction-clp Modelmentioning

confidence: 99%

Characterization and modulation of microglial phenotypes in an animal model of severe sepsis

Michels¹,

Abatti²,

Ávila³

et al. 2019

J Cellular Molecular Medi

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We aim to characterize the kinetics of early and late microglial phenotypes after systemic inflammation in an animal model of severe sepsis and the effects of minocycline on these phenotypes. Rats were subjected to CLP, and some animals were treated with minocycline (10 ug/kg) by i.c.v. administration. Animals were killed 24 hours, 5, 10 and 30 days after sepsis induction, and serum and hippocampus were collected for subsequent analyses. Real‐time PCR was performed for M1 and M2 markers. TNF‐α, IL‐1β, IL‐6, IL‐10, CCL‐22 and nitrite/nitrate levels were measured. Immunofluorescence for IBA‐1, CD11b and arginase was also performed. We demonstrated that early after sepsis, there was a preponderant up‐regulation of M1 markers, and this was not switched to M2 phenotype markers later on. We found that up‐regulation of both M1 and M2 markers co‐existed up to 30 days after sepsis induction. In addition, minocycline induced a down‐regulation, predominantly, of M1 markers. Our results suggest early activation of M1 microglia that is followed by an overlap of both M1 and M2 phenotypes and that the beneficial effects of minocycline on sepsis‐associated brain dysfunction may be related to its effects predominantly on the M1 phenotype.

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“…We had demonstrated previously that the control of acute inflammation was associated with improved long-term outcome in the CLP model of sepsis (45)(46)(47). Here we demonstrated that the downregulation of CD40 signaling was able to improve long-term cognitive function in sepsis survivor rats.…”

Section: Discussionmentioning

confidence: 59%

CD40-CD40 Ligand Pathway Is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis

Michels

Danieslki

Vieira

et al. 2015

Mol Med

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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.

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Correlation of Acute Phase Inflammatory and Oxidative Markers With Long-term Cognitive Impairment in Sepsis Survivors Rats

Cited by 35 publications

References 28 publications

Evaluation of NCS-1, DARPP-32, and neurotrophins in hippocampus and prefrontal cortex in rats submitted to sepsis

Evaluation of NCS-1, DARPP-32, and neurotrophins in hippocampus and prefrontal cortex in rats submitted to sepsis

Characterization and modulation of microglial phenotypes in an animal model of severe sepsis

CD40-CD40 Ligand Pathway Is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis

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