High concentrations of fructose cause brain damage in mice.

Excessive fructose consumption is associated with the incidence of obesity and systemic inflammation, resulting in increased oxidative damage and failure to the function of brain structures. Thus, we hypothesized that fructose consumption will significantly increase inflammation, oxidative damage, and mitochondrial dysfunction in the mouse brain and, consequently, memory damage. The effects of different fructose concentrations on inflammatory and biochemical parameters in the mouse brain were evaluated. Male Swiss mice were randomized into four groups: control, with exclusive water intake, 5%, 10%, and 20% fructose group. The 10% and 20% fructose groups showed an increase in epididymal fat, in addition to higher food consumption. Inflammatory markers were increased in epididymal fat and in some brain structures. In the evaluation of oxidative damage, it was possible to observe significant increases in the hypothalamus, prefrontal cortex, and hippocampus. In the epididymal fat and in the prefrontal cortex, there was a decrease in the activity of the mitochondrial respiratory chain complexes and an increase in the striatum. Furthermore, short memory was impaired in the 10% and 20% groups but not long memory. In conclusion, excess fructose consumption can cause fat accumulation, inflammation, oxidative damage, and mitochondrial dysfunction, which can damage brain structures and consequently memory.

The effect of modafinil on passive avoidance memory, brain level of BDNF and oxidative stress markers in sepsis survivor rats.

Propose/aim of study: Modafinil (MD) is a psychostimulant drug used off-label and cognitive dysfunction may be a significant emerging treatment target for this drug. The objective of this study was to evaluate the effect of MD on the neurochemical parameters and memory impairment of rats submitted to sepsis by cecal ligation and perforation (CLP).Material and method: Male Wistar rats (250-350g) were submitted to CLP, or sham as control, and divided into the sham + water, sham + MD (300 mg/kg), CLP + water, and CLP + MD (300 mg/kg) groups. Ten days after the administration of MD and CLP, the rats were submitted to a memory test by passive avoidance apparatus being sacrificed. The nitrite and nitrate (N/N) concentration, myeloperoxidase (MPO) and catalase (CAT) activity, lipid and protein oxidative damage, and brain-derived neurotrophic factor (BDNF) levels were measured in the prefrontal cortex and hippocampus.Results: The passive avoidance test verified an increase in the latency time compared training and test section in the groups sham + water and CLP + MD. Decreased N/N concentration and MPO activity were verified in the prefrontal cortex of rats submitted to CLP and MD treatment, as well as reduced protein and lipid oxidative damage in the hippocampus, which was accompanied by increased CAT activity and BDNF levels.Conclusion: Our data indicate the role of MD in attenuating oxidative stress parameters, the alteration of BDNF, and an improvement in memory impairment in rats ten days after induction of sepsis.

The Infected Lungs and Brain Interface in COVID-19: The Impact on Cognitive Function.

Many coronavirus disease 2019 (COVID-19)-recovered patients report signs and symptoms and are experiencing neurological, psychiatric, and cognitive problems. However, the exact prevalence and outcome of cognitive sequelae is unclear. Even though the severe acute respiratory syndrome coronavirus 2 has target brain cells through binding to angiotensin-converting enzyme 2 (ACE2) receptor in acute infection, several studies indicate the absence of the virus in the brain of many COVID-19 patients who developed neurological disorders. Thus, the COVID-19 mechanisms for stimulating cognitive dysfunction may include neuroinflammation, which is mediated by a sustained systemic inflammation, a disrupted brain barrier, and severe glial reactiveness, especially within the limbic system. This review explores the interplay of infected lungs and brain in COVID-19 and its impact on the cognitive function.

Lung-Brain Crosstalk in Sepsis: Protective Effect of Prophylactic Physical Exercise Against Inflammation and Oxidative Stress in Rats.

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. The crosstalk occurs between the primary focus of infection and lung and other organ systems including the central nervous system via soluble and cellular inflammatory mediators and that this involves both the innate and adaptive immune systems. These interactions are reflected by genomic changes and abnormal rates of cellular apoptosis. The lungs and the brain are rapidly affected due to an inflammatory response and oxidative stress in sepsis. Physical exercise promotes positive responses in the inflammatory cascade and oxidative/antioxidant system. In this sense, we aimed at determining the possible protectant effects of a physical exercise program against inflammation and oxidative stress on the lungs and the brain of rats subjected to sepsis. Adult male Wistar rats were randomly assigned to the sham + sedentary (S), sham + trained (T), and cecal ligation and perforation (CLP) + S and CLP + T and subjected to a physical exercise program using a treadmill for 21 days. Forty-eight hours after the last training session, sepsis was induced by the CLP model. Twenty-four hours later, the animals were euthanized and the lungs, the hippocampus, and the prefrontal cortex were harvested to determine the levels of cytokines by enzyme-linked immunosorbent assay (ELISA) and nitrite and reactive oxygen species production, oxidative damage to proteins, and antioxidant enzymes by spectrophotometric method. Sepsis increased the lung and brain levels of TNF-α, IL-1ß, and IL-6, while diminished IL-10 levels, elevated nitrite levels and reactive oxygen species production, augmented the levels of protein carbonyls and diminished the sulfhydryl content, and decreased SOD activity and GSH levels. The exercise program diminished the levels of TNF-α, IL-1ß, IL-6, nitrite, and reactive oxygen species production, as well as the levels of protein carbonyls but augmented the sulfhydryl content, and elevated SOD activity. In conclusion, the exercise program protected the lungs and the brain of septic rats against inflammation and oxidative stress.

Oxidative stress in multiple organs after sepsis in elderly rats.

Aging is a dynamic process, in which morphological and physiological changes occur at all levels, making the body more vulnerable to acute events. Elderly people are at greater risk of sepsis developing than younger people. Sepsis is a set of serious manifestations throughout the body produced by an infection, leading to events that compromise cell homeostasis as oxidative stress and is associated with organ dysfunction. The aim of this study was to evaluate multi-organ oxidative stress in old rats in an animal model of polymicrobial sepsis. Adult (60d) and old (210d) male Wistar rats were submitted to sepsis by cecal ligation and perforation (CLP) and control group (sham) only by laparotomy. The experimental groups were divided into sham 60d, sham 210d, CLP 60d and CLP 210d. Twenty-four hours after CLP, myeloperoxidase (MPO) activity, oxidative damage to lipids and proteins, superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in the lung, kidney, liver, heart, spleen, quadriceps and diaphragm. Aging potentiated the increase in MPO activity in the after sepsis in the lung, liver and spleen. Lipid oxidative damage occurred in all structures analyzed in the CLP groups, while only in the lung, liver and diaphragm the lipid peroxidation was higher in the CLP 210d group compared to 60d. Regarding protein damage, this potentiation happened only in the lung. The SOD activity in the lung, kidney, spleen and diaphragm there was a significant decrease in the CLP 210d group compared to the sham 60d group while in the CAT only in the lung and kidney. The findings in this study indicate that increasing age potentiated oxidative damage in different organs after sepsis by intensifying the presence of neutrophils, which possibly increased the damage to lipids and proteins with reduced activity of SOD and CAT.

Sexually transmitted infections in indigenous communities of the Alto Rio Solimões / Infecções sexualmente transmissíveis em comunidades indígenas do Alto Rio Solimões

Introduction: The prevalence of sexually transmitted infections (STI) among indigenous communities is an appalling issue related to Brazilian public health, as there is an increasing underreporting and neglect related to the study and care of these people. Objective: To determine the prevalence of STI in the indigenous population of the Alto Rio Solimões. Methods: STI diagnostic records from the database of the Indigenous Health Care Information System - SIASI, of the indigenous communities of the Alto Rio Solimões, belonging to the Nova Itália base, in Amazonas, were evaluated during the period from January 2010 to August 2020. Sociodemographic data were also evaluated to determine the profile of the diagnosed indigenous population and the geographical and temporal distribution of cases. Results: The overall prevalence rate of STIs was 3.91% (113 notifications of STI in the population of 2890 indigenous people). The largest number of diagnosed cases was in Nova Itália (60.17%). The ethnic group with the highest number of cases was Tikuna (92.03%). Among the STI studied, gonorrhea / chlamydia had the highest prevalence (68.14%), followed by Hepatitis B (13.27%) and Syphilis (10.61%). Most cases were found among women (71.7%), aged 30­34 years. Conclusion: A higher prevalence of STIs was observed in indigenous women, mainly from the Nova Itália town and the Tikuna ethnic group.

Introdução: A prevalência das infecções sexualmente transmissíveis (IST) entre comunidades indígenas é um tema consternador relacionado à saúde pública brasileira, pois há crescente subnotificação e negligência relacionada ao estudo e ao cuidado desses povos. Objetivo: Determinar a prevalência de IST na população indígena do Alto Rio Solimões. Métodos: Foram avaliados os registros diagnósticos de IST da base de dados do Sistema de Informação da Atenção à Saúde Indígena (SIASI), das comunidades indígenas do Alto Rio Solimões, pertencentes ao polo-base de Nova Itália, no Amazonas, durante o período de janeiro de 2010 a agosto de 2020. Também foram avaliados dados sociodemográficos para determinação do perfil da população indígena diagnosticada e a distribuição geográfica e temporal dos casos. Resultados: A taxa de prevalência geral de IST foi de 3,91% (113 notificações de IST na população de 2.890 indígenas). O maior número de casos diagnosticados foi em Nova Itália (60,17%). A etnia com maiores números de casos foi a Tikuna (92,03%). Entre as IST estudadas, gonorreia/clamídia tiveram a maior prevalência (68,14%), seguidas por hepatite B (13,27%) e sífilis (10,61%). A maioria dos casos ocorreu entre mulheres (71,7%) e na faixa de 30­34 anos. Conclusão: Observou-se maior prevalência de IST em mulheres indígenas, principalmente do município de Nova Itália e da etnia Tikuna

Depressão em dependentes químicos: uma revisão sistemática da literatura / Depression in drug addicts: a systematic literature review

Introdução: A coocorrência entre o abuso de substâncias químicas e o transtorno depressivo é reconhecida cada vez mais como um problema de saúde pública em âmbito mundial. Objetivos: Compreender a problemática da depressão no dependente químico, segundo uma análise da literatura nacional e internacional. Método: Realizou-se uma revisão de artigos científicos publicados nas seguintes plataformas de pesquisa: Portal de Periódicos Eletrônicos de Psicologia (PePSIC), Cochrane Collaboration e Scientific Electronic Library Online (SCIELO). Resultados: Foram encontrados 83 estudos relacionados aos descritores utilizados, sendo que, após a primeira e segunda análise de adequação aos objetivos da revisão, restaram oito. Os resultados evidenciaram que a prevalência de transtornos depressivos nos dependentes químicos teve uma média de 21,27%. O método diagnóstico utilizado com maior frequência foi o Inventário de Depressão de Beck (30%). Conclusão: Constatou-se que a prevalência de transtornos depressivos em dependentes químicos é de aproximadamente três vezes o da população em geral. Verificou-se que as "avaliações rápidas", como os instrumentos MINI e Inventário de Depressão de Beck, foram as mais utilizadas para realização do diagnóstico de depressão na pessoa com dependência química.

Introduction: The co-occurrence between substance abuse and depressive disorder is increasingly recognized as a public health problem worldwide. Objectives: To understand the problem of depression in drug addicts according to an analysis of national and international literature. Method: A review of scientific articles published in the following research platforms was carried out: Psychology Electronic Journal Portal (PePSIC), Cochrane Collaboration, and Scientific Electronic Library Online (SCIELO). Results: Eighty-three studies related to the keywords used were found, and after the first and second analysis of adequacy to the review objectives, eight remained. The results showed that the prevalence of depressive disorders in drug addicts had an average of 21.27%. The most frequently used diagnostic method was the Beck Depression Inventory (30%). Conclusions: It was found that the prevalence of depressive disorders in drug addicts is approximately three times that of the general population. It was found that "quick assessments" such as the MINI and the Beck Depression Inventory were the most used to diagnose depression in people with drug addiction.

Folic acid alleviates the blood brain barrier permeability and oxidative stress and prevents cognitive decline in sepsis-surviving rats.

Sepsis is a complication of an infection which imbalance the normal regulation of several organ systems, including the central nervous system (CNS). Evidence points towards inflammation and oxidative stress as major steps associated with brain dysfunction in sepsis. Thus, we investigated the folic acid (FA) effect as an important antioxidant compound on acute brain dysfunction in rats and long term cognitive impairment and survival. Wistar rats were subjected to sepsis by cecal ligation and perforation (CLP) or sham (control) and treated orally with FA (10 mg/kg after CLP) or vehicle (veh). Animals were divided into sham + veh, sham + FA, CLP + veh and CLP + FA groups. Twenty-four hours after surgery, the hippocampus and prefrontal cortex were obtained and assayed for levels of blood brain barrier (BBB) permeability, nitrite/nitrate concentration, myeloperoxidase (MPO) activity, thiobarbituric acid reactive species (TBARS) formation and protein carbonyls. Survival was performed during 10 days after surgery and memory was evaluated. FA reduced BBB permeability, MPO activity in hippocampus and pre frontal cortex in 24 h and lipid peroxidation in hippocampus and improves the survival rate after sepsis. Long term cognitive improvement was verified with FA in septic rats compared with CLP + veh. Our data demonstrates that FA reduces the memory impairment in 10 days after sepsis and mortality in part by decreasing BBB permeability and oxidative stress parameters in the brain.

Ketamine treatment protects against oxidative damage and the immunological response induced by electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is often recommended for major depressive disorder (MDD) for those who do not respond to the first and second antidepressant trials. A combination of two therapies could improve antidepressant efficacy. Thus, this study aimed to investigate the synergistic effects of ECT combined to antidepressants with a different mechanism of action. METHODS: Rats were treated once a day, for five days with ketamine (5 mg/kg), fluoxetine (1 mg/kg), and bupropion (4 mg/kg) alone or in combination with ECT (1 mA; 100 V). After, oxidative damage and antioxidant capacity were assessed in the prefrontal cortex (PFC) and hippocampus, and pro-inflammatory cytokines levels were evaluated in the serum. RESULTS: ECT alone increased lipid peroxidation in the PFC and hippocampus. In the PFC of rats treated with ECT in combination with fluoxetine and bupropion, and in the hippocampus of rats treated with ECT combined with ketamine and bupropion there was a reduction in the lipid peroxidation. The nitrite/nitrate was increased by ECT alone but reverted by combination with ketamine in the hippocampus. Superoxide dismutase (SOD) was increased by ECT and maintained by fluoxetine and bupropion in the PFC. ECT alone increased interleukin-1ß (IL-1ß) and the administration of ketamine was able to revert this increase showing a neuroprotective effect of this drug when in combination with ECT. CONCLUSION: The treatment with ECT leads to an increase in oxidative damage and alters the immunological system. The combination with ketamine was able to protect against oxidative damage and the immunological response induced by ECT.

Post-Match Recovery in Soccer with Far-Infrared Emitting Ceramic Material or Cold-Water Immersion.

We investigated the effects of two common recovery methods; far-infrared emitting ceramic materials (Bioceramic) or cold-water immersion on muscular function and damage after a soccer match. Twenty-five university-level soccer players were randomized into Bioceramic (BIO; n = 8), Cold-water immersion (CWI; n = 9), or Control (CON; n = 8) groups. Heart rate [HR], rating of perceived exertion [RPE], and activity profile through Global Positioning Satellite Systems were measured during the match. Biochemical (thiobarbituric acid reactive species [TBARS], superoxide dismutase [SOD], creatine kinase [CK], lactate dehydrogenase [LDH]), neuromuscular (countermovement [CMJ] and squat jump [SJ], sprints [20-m]), and perceptual markers (delayed-onset muscle soreness [DOMS], and the perceived recovery scale [PRS]) were assessed at pre, post, 24 h, and 48 h post-match. One-way ANOVA was used to compare anthropometric and match performance data. A two-way ANOVA with post-hoc tests compared the timeline of recovery measures. No significant differences existed between groups for anthropometric or match load measures (P > 0.05). Significant post-match increases were observed in SOD, and decreases in TBARS in all groups (p < 0.05), without differences between conditions (p > 0.05). Significant increases in CK, LDH, quadriceps and hamstring DOMS (p < 0.05), as well as decreases in 20-m, SJ, CMJ, and PRS were observed post-match in all groups (p < 0.05), without significant differences between conditions (p > 0.05). Despite the expected post-match muscle damage and impaired performance, neither Bioceramic nor CWI interventions improved post-match recovery.

Stanniocalcin 1 Inhibits the Inflammatory Response in Microglia and Protects Against Sepsis-Associated Encephalopathy.

Sepsis-associated encephalopathy is a serious consequence of sepsis, triggered by the host response against an infectious agent, that can lead to brain damage and cognitive impairment. Several mechanisms have been proposed in this bidirectional communication between the immune system and the brain after sepsis as neuroinflammation, oxidative stress, and mitochondrial dysfunction. Stanniocalcin-1 (STC-1), an endogen neuroprotective protein, acts as an anti-inflammatory and suppresses superoxide generation through induction of uncoupling proteins (UCPs) in the mitochondria. Here, we demonstrated a protective role of STC-1 on inflammatory responses in vitro, in activated microglia stimulated with LPS, and on neuroinflammation, oxidative stress, and mitochondrial function in the hippocampus of rats subjected to an animal model of sepsis by cecal ligation and puncture (CLP), as well the consequences on long-term memory. Recombinant human STC-1 (rhSTC1) suppressed the pro-inflammatory cytokine production in LPS-stimulated microglia without changing the UCP-2 expression. Besides, rhSTC1 injected into the cisterna magna decreased acute hippocampal inflammation and oxidative stress and increased the activity of complex I and II activity of mitochondrial respiratory chain and creatine kinase at 24 h after sepsis. rhSTC1 was effective in preventing long-term cognitive impairment after CLP. In conclusion, rhSTC1 confers significant neuroprotection by inhibiting the inflammatory response in microglia and protecting against sepsis-associated encephalopathy in rats.

NLRP3 Activation Contributes to Acute Brain Damage Leading to Memory Impairment in Sepsis-Surviving Rats.

Sepsis survivors present acute and long-term cognitive impairment and the pathophysiology of neurological dysfunction in sepsis involves microglial activation. Recently, the involvement of cytosolic receptors capable of forming protein complexes called inflammasomes have been demonstrated to perpetuate neuroinflammation. Thus, we investigated the involvement of the NLRP3 inflammasome activation on early and late brain changes in experimental sepsis. Two-month-old male Wistar rats were submitted to the sepsis model by cecal ligation and perforation (CLP group) or laparotomy only (sham group). Immediately after surgery, the animals received saline or NLRP3 inflammasome formation inhibitor (MCC950, 140 ng/kg) intracerebroventricularly. Prefrontal cortex and hippocampus were isolated for cytokine analysis, microglial and astrocyte activation, oxidative stress measurements, nitric oxide formation, and mitochondrial respiratory chain activity at 24 h after CLP. A subset of animals was followed for 10 days for survival assessment, and then behavioral tests were performed. The administration of MCC950 restored the elevation of IL-1ß, TNF-α, IL-6, and IL-10 cytokine levels in the hippocampus. NLRP3 receptor levels increased in the prefrontal cortex and hippocampus at 24 h after sepsis, associated with microglial, but not astrocyte, activation. MCC950 reduced oxidative damage to lipids and proteins as well as preserved the activity of the enzyme SOD in the hippocampus. Mitochondrial respiratory chain activity presented variations in both structures studied. MCC950 reduced microglial activation, decreased acute neurochemical and behavioral alteration, and increased survival after experimental sepsis.

Lipoic Acid and Fish Oil Combination Potentiates Neuroinflammation and Oxidative Stress Regulation and Prevents Cognitive Decline of Rats After Sepsis.

Sepsis causes organ dysfunction due to an infection, and it may impact the central nervous system. Neuroinflammation and oxidative stress are related to brain dysfunction after sepsis. Both processes affect microglia activation, neurotrophin production, and long-term cognition. Fish oil (FO) is an anti-inflammatory compound, and lipoic acid (LA) is a universal antioxidant substance. They exert neuroprotective roles when administered alone. We aimed at determining the effect of FO+LA combination on microglia activation and brain dysfunction after sepsis. Microglia cells from neonatal pups were co-treated with lipopolysaccharide (LPS) and FO or LA, alone or combined, for 24 h. Cytokine levels were measured. Wistar rats were subjected to sepsis by cecal ligation and perforation (CLP) and treated orally with FO, LA, or FO+LA. At 24 h after surgery, the hippocampus, prefrontal cortex, and total cortex were obtained and assayed for levels of cytokines, myeloperoxidase (MPO) activity, protein carbonyls, superoxide dismutase (SOD), and catalase (CAT) activity. At 10 days after surgery, brain-derived neurotrophic factor (BDNF) levels were determined and behavioral tests were performed. The combination diminished in vitro levels of pro-inflammatory cytokines. The combination reduced TNF-α in the cortex, IL-1ß in the prefrontal cortex, as well as MPO activity, and decreased protein carbonyls formation in all structures. The combination enhanced catalase activity in the prefrontal cortex and hippocampus, elevated BDNF levels in all structures, and prevented behavioral impairment. In summary, the combination was effective in preventing cognitive damage by reducing neuroinflammation and oxidative stress and increasing BDNF levels.

Donepezil Prevents Inhibition of Cerebral Energetic Metabolism Without Altering Behavioral Parameters in Animal Model of Obesity.

Obesity is characterized by chronic inflammation of low grade. The cholinergic anti-inflammatory pathway favors the reduction of the inflammatory response. In this work the effect of stimulation of the cholinergic anti-inflammatory pathway on SHIRPA behavioral test and mitochondrial respiratory chain activity in obese mice was evaluated. The animals were paired in four groups: saline + control diet; donepezil + control diet; saline + high-fat diet and donepezil + high-fat diet. 5 mg/kg/day orally of donepezil or saline were given 7 days before the beginning of the diet until completing 11 weeks of the experiment. Food intake and body weight were measured. At the end of the experiment the animals were submitted to the SHIRPA behavioral test, soon after they were killed by decapitation, the open abdominal cavity and the mesenteric fat were removed. The hypothalamus, hippocampus, prefrontal cortex, and striatum were removed for evaluation of the mitochondrial respiratory chain. It can be observed that donepezil prevented weight gain and food consumption, as well as a tendency to prevent the accumulation of mesenteric fat in obese animals. There was no behavioral change in obese animals, nor did the influence of donepezil on these parameters. On the other hand, donepezil did not prevent inhibition of complex I activity, prevented the inhibition of complex II, and showed a tendency to prevent IV complex activity inhibited in obesity. With these results it can be concluded that the activation of the cholinergic anti-inflammatory pathway is promising for the alterations found in obesity.

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

Sepsis is a set of serious manifestations throughout the body produced by an infection, leading to changes that compromise cellular homeostasis and can result in dysfunction of the central nervous system. The elderly have a higher risk of developing sepsis than younger peoples. Under the influence of inflammatory mediators and oxidizing agents released in the periphery as a result of the infectious stimulus, changes occur in the blood-brain barrier (BBB) permeability, with neutrophil infiltration, the passage of toxic compounds, activation of microglia and production of reactive species that results in potentiation of neuroimmune response, with the progression of neuronal damage and neuroinflammation. The objective of this study is to compare BBB permeability and the development of oxidative stress in the hippocampus and prefrontal cortex of young and old rats submitted to polymicrobial sepsis induction. Male Wistar rats grouped into sham (60d), sham (210d), cecal ligation and perforation (CLP) (60d) and CLP (210d) with n = 16 per experimental group were evaluated using the CLP technique to induce sepsis. The brain regions were collected at 24 h after sepsis induction to determine BBB permeability, myeloperoxidase (MPO) activity as marker of neutrophil activation, nitrite/nitrate (N/N) levels as marker of reactive nitrogen species, thiobarbituric acid reactive substances as marker of lipid peroxidation, protein carbonylation as marker of protein oxidation, and activity of antioxidant enzyme catalase (CAT). There was an increase in the BBB permeability in the CLP groups, and this was enhanced with aging in both brain region. MPO activity in the brain regions increased in the CLP groups, along with a hippocampal increase in the CLP 210d group compared to the 60d group. The concentration of N/N in the brain region was increased in the CLP groups. The damage to lipids and proteins in the two structures was enhanced in the CLP groups, while only lipid peroxidation was higher in the prefrontal cortex of the CLP 210d group compared to the 60d. CAT activity in the hippocampus was decreased in both CLP groups, and this was also influenced by age, whereas in the prefrontal cortex there was only a decrease in CAT in the CLP 60d group compared to the sham 60d. These findings indicate that aging potentiated BBB permeability in sepsis, which possibly triggered an increase in neutrophil infiltration and, consequently, an increase in oxidative stress.

Early life neuroimmune challenge protects the brain after sepsis in adult rats.

Evidences has suggested that in the early life the innate immune system presents plasticity and the time and dose-adequate stimuli in this phase may program long-lasting immunological responses that persist until adulthood. We aimed to evaluate whether LPS challenge in early childhood period may modulate brain alterations after sepsis in adult life. Experiments were performed to evaluate the LPS challenge in early childhood or adult period on acute and long-term brain alterations after model of sepsis by cecal ligation and perforation (CLP) in adult life. Wistar rats were divided in saline+sham, LPS+sham, saline+CLP and LPS+CLP groups to determine cytokine levels and nitrite/nitrate concentration in cerebrospinal fluid (CSF); oxidative damage, activity of antioxidant enzymes (superoxide dismutase-SOD and catalase-CAT); blood brain barrier (BBB) permeability; myeloperoxidase (MPO) and epigenetic enzymes activities in the hippocampus and prefrontal cortex (at 24 h after CLP) and cognitive function, survival and brain-derived neurotrophic factor (BDNF) level (at ten days after CLP). LPS-preconditioning in early life could lead to decreased levels of TNF-α and IL-6 and oxidative damage parameters in the brain after CLP in adult rats. In addition, LPS-preconditioning in early life increase CAT activity, attenuates the BBB permeability and epigenetic enzymes alterations and in long term, improves the memory, BDNF levels and survival. In conclusion, rats submitted to CLP in adulthood displayed acute neuroinflammation, neurochemical and epigenetic alteration improvement accompanied in long term by an increase in survival, neurotrophin level and memory performance when preconditioned with LPS in the early life.

Sickness Behavior Score Is Associated with Neuroinflammation and Late Behavioral Changes in Polymicrobial Sepsis Animal Model.

The use of reliable scores is a constant development in critical illness. According to Sepsis-3 consensus, the use of Sequential Organ Failure Assessment (SOFA) score of 2 or more is associated with a higher mortality of sepsis patients. In experimental research, due murine animal model limitations, the use of a score systems can be an alternative to assess sepsis severity. In this work, we suggest a sickness behavior score (SBS) that uses physiological variables to assess sepsis severity and mortality. Animals were evaluated daily by the presence of six indicators of sickness behavior: temperature alteration, preference of water/sucrose, liquid intake, food intake, body weight, and movimentation. Male adult Wistar rats were evaluated daily after sepsis induction by cecal ligation and puncture (CLP) or laparotomy only (sham) for determination of SBS. Oxidative stress, IL-6, and HPA axis markers (corticosterone and adrenal gland weight) were evaluated 24 h after CLP to determine the correlation with the acute SBS and neuroinflammation. Also, BDNF and four cognitive behavioral tests were correlated with the chronic SBS, i.e., sum of 8 days after surgery. In result, septic rats presented higher SBS than sham animals. Sepsis severity markers were associated with acute and chronic SBS. Also, SBS was negative correlated with the cognitive tests. In conclusion, SBS shows to be reliable score to predict sepsis severity and mortality. The use of score system provides the analysis of global sickness behavior, beyond evaluation of each parameter individually.

Gold nanoparticles potentiates N-acetylcysteine effects on neurochemicals alterations in rats after polymicrobial sepsis.

Herein, we report the effect of gold nanoparticles (AuNP) and n-acetylcysteine (NAC) isolated or in association as important anti-inflammatory and antioxidant compounds on brain dysfunction in septic rats. Male Wistar rats after sham operation or caecal ligation and perforation (CLP) were treated with subcutaneously injection of AuNP (50 mg/kg) and/or NAC (20 mg/kg) or saline immediately and 12 h after surgery. Twenty-four hours after CLP, hippocampus and prefrontal cortex were obtained and assayed for myeloperoxidase (MPO) activity, cytokines, lipid peroxidation, protein carbonyls formation, mitochondrial respiratory chain, and CK activity. AuNP + NAC association decreased MPO activity and pro-inflammatory cytokines production, being more effective than NAC or AuNP isolated treatment. AuNP + NAC association and NAC isolated treatment decreased oxidative stress to lipids in both brain structures, while protein oxidation decreased only in the hippocampus of AuNP + NAC association-treated animals. Complex I activity was increased with AuNP + NAC association and NAC isolated in the hippocampus. Regarding CK activity, AuNP and AuNP + NAC association increased this marker in both brain structures after CLP. Our data provide the first experimental demonstration that AuNP and NAC association was able to reduce sepsis-induced brain dysfunction in rats by decreasing neuroinflammation, oxidative stress parameters, mitochondrial dysfunction and CK activity.

Fish oil-rich lipid emulsion modulates neuroinflammation and prevents long-term cognitive dysfunction after sepsis.

OBJECTIVES: Sepsis is a severe organic dysfunction caused by an infection that affects the normal regulation of several organ systems, including the central nervous system. Inflammation and oxidative stress play crucial roles in the development of brain dysfunction in sepsis. The aim of this study was to determine the effect of a fish oil (FO)-55-enriched lipid emulsion as an important anti-inflammatory compound on brain dysfunction in septic rats. METHODS: Wistar rats were subjected to sepsis by cecal ligation and perforation (CLP) or sham (control) and treated orally with FO (600 µL/kg after CLP) or vehicle (saline; sal). Animals were divided into sham+sal, sham+FO, CLP+sal and CLP+FO groups. At 24 h and 10 d after surgery, the hippocampus, prefrontal cortex, and total cortex were obtained and assayed for levels of interleukin (IL)-1ß and IL-10, blood-brain barrier permeability, nitrite/nitrate concentration, myeloperoxidase activity, thiobarbituric acid reactive species formation, protein carbonyls, superoxide dismutase and catalase activity, and brain-derived neurotrophic factor levels. Behavioral tasks were performed 10 d after surgery. RESULTS: FO reduced BBB permeability in the prefrontal cortex and total cortex of septic rats, decreased IL-1ß levels and protein carbonylation in all brain structures, and diminished myeloperoxidase activity in the hippocampus and prefrontal cortex. FO enhanced brain-derived neurotrophic factor levels in the hippocampus and prefrontal cortex and prevented cognitive impairment. CONCLUSIONS: FO diminishes the negative effect of polymicrobial sepsis in the rat brain by reducing inflammatory and oxidative stress markers.