Bacillus Calmette-Guérin (BCG)-Induced Protection in Brain Disorders.

The Bacille Calmette-Guerin (BCG) vaccine is one of the most widely used vaccines in the world for the prevention of tuberculosis. Its immunological capacity also includes epigenetic reprogramming, activation of T cells and inflammatory responses. Although the main usage of the vaccine is the prevention of tuberculosis, different works have shown that the effect of BCG can go beyond the peripheral immune response and be linked to the central nervous system by modulating the immune system at the level of the brain. This review therefore aims to describe the BCG vaccine, its origin, its relationship with the immune system, and its involvement at the brain level.

Hyperoxia and brain: the link between necessity and injury from a molecular perspective.

Oxygen (O2) supplementation is commonly used to treat hypoxia in patients with respiratory failure. However, indiscriminate use can lead to hyperoxia, a condition detrimental to living tissues, particularly the brain. The brain is sensitive to reactive oxygen species (ROS) and inflammation caused by high concentrations of O2, which can result in brain damage and mitochondrial dysfunction, common features of neurodegenerative disorders. Hyperoxia leads to increased production of ROS, causing oxidative stress, an imbalance between oxidants and antioxidants, which can damage tissues. The brain is particularly vulnerable to oxidative stress due to its lipid composition, high O2 consumption rate, and low levels of antioxidant enzymes. Moreover, hyperoxia can cause vasoconstriction and decreased O2 supply to the brain, posing a challenge to redox balance and neurodegenerative processes. Studies have shown that the severity of hyperoxia-induced brain damage varies with inspired O2 concentration and duration of exposure. Therefore, careful evaluation of the balance between benefits and risks of O2 supplementation, especially in clinical settings, is crucial.

Short-term hyperoxia induced mitochondrial respiratory chain complexes dysfunction and oxidative stress in lung of rats.

BACKGROUND: Oxygen therapy is an alternative for many patients with hypoxemia. However, this practice can be dangerous as oxygen is closely associated with the development of oxidative stress. METHODS: Male Wistar rats were exposed to hyperoxia with a 40% fraction of inspired oxygen (FIO2) and hyperoxia (FIO2 = 60%) for 120 min. Blood and lung tissue samples were collected for gas, oxidative stress, and inflammatory analyses. RESULTS: Hyperoxia (FIO2 = 60%) increased PaCO2 and PaO2, decreased blood pH and caused thrombocytopenia and lymphocytosis. In lung tissue, neutrophil infiltration, nitric oxide concentration, carbonyl protein formation and the activity of complexes I and II of the mitochondrial respiratory chain increased. FIO2 = 60% decreased SOD activity and caused several histologic changes. CONCLUSION: In conclusion, we have experimentally demonstrated that short-term exposure to high FIO2 can cause oxidative stress in the lung.

Cannabidiol effect on long-term brain alterations in septic rats: Involvement of PPARγ activation.

Sepsis is a life-threatening condition induced by a deregulated host response to infection. Post-sepsis injury includes long-term cognitive impairment, whose neurobiological mechanisms and effective treatment remain unknown. The present study was designed to determine the potential effects of cannabidiol (CBD) in a sepsis-associated encephalopathy (SAE) model and explore if peroxisome proliferator activated receptor gamma (PPARγ) is the putative mechanism underpinning the beneficial effects. SAE was induced in Wistar rats by cecal ligation and puncture (CLP) or sham (control). CLP rats received vehicle, CBD (10 mg/kg), PPARγ inhibitor (GW9662 - 1 mg/kg), or GW9662 (1 mg/kg) + CBD (10 mg/kg) intraperitoneally for ten days. During this period, the survival rate was recorded, and at the end of 10 days, a memory test was performed, and the prefrontal cortex and hippocampus were removed to verify brain-derived neurotrophic factor (BDNF), cytokines (IL-1ß, IL-6 and IL-10), myeloperoxidase activity, nitrite nitrate concentration, and lipid and protein carbonylation and catalase activity. Septic rats presented cognitive decline and an increase in mortality following CLP. Only CBD alone improved the cognitive impairment, which was accompanied by restoration of BDNF, reduced neuroinflammation, and oxidative stress, mainly in the hippocampus. This study shows that CLP induces an increase in brain damage and CBD has neuroprotective effects on memory impairment and neurotrophins, as well as against neuroinflammation and oxidative stress, and is mediated by PPARγ activation.

Blood-brain barrier permeability in the ischemic stroke: An update.

Stroke is the second leading cause of death globally and the major cause of long-term disability. Among the types of strokes, ischemic stroke, which occurs due to obstruction of blood vessels responsible for cerebral irrigation, is considered the most prevalent, accounting for approximately 86 % of all stroke cases. This interruption of blood supply leads to a critical pathophysiological mechanism, including oxidative stress and neuroinflammation which are responsible for structural alterations of the blood-brain barrier (BBB). The increased BBB permeability associated with cerebral ischemia-reperfusion may contribute to a worse outcome after stroke. Thus, this narrative review aims to update the pathophysiological mechanisms involved in the increase in BBB permeability and to list the possible therapeutic strategies.

From diabetic hyperglycemia to cerebrovascular Damage: A narrative review.

Diabetes mellitus is a globally significant disease that can lead to systemic complications, particularly vascular damage, including cardiovascular and cerebrovascular diseases of relevance. The physiological changes resulting from the imbalance in blood glucose levels play a crucial role in initiating vascular endothelial damage. Elevated glucose levels can also penetrate the central nervous system, triggering diabetic encephalopathy characterized by oxidative damage to brain components and activation of alternative and neurotoxic pathways. This brain damage increases the risk of ischemic stroke, a leading cause of mortality worldwide and a major cause of disability among surviving patients. The aim of this review is to highlight important pathways related to hyperglycemic damage that extend to the brain and result in vascular dysfunction, ultimately leading to the occurrence of a stroke. Understanding how diabetes mellitus contributes to the development of ischemic stroke and its impact on patient outcomes is crucial for implementing therapeutic strategies that reduce the incidence of diabetes mellitus and its complications, ultimately decreasing morbidity and mortality associated with the disease.

NLRP3 inflammasome activation increases brain oxidative stress after transient global cerebral ischemia in rats.

Pupurpose of the study: Oxidative stress has been reported to be an important mechanism for brain damage following ischemic stroke. Recently, the involvement of cytosolic receptors capable of forming protein complexes called inflammasomes has been demonstrated to perpetuate oxidative stress. Herein, we report the effect of NLRP3 inhibition with MCC950 on brain oxidative stress in an animal model of transient global cerebral ischemia.Materials and methods: Male Wistar rats received an intracerebroventricularly (icv) injection of MCC950 (140 ng/kg) or saline and were subjected to sham procedure or ischemia/reperfusion (I/R). Twenty-four hours after I/R, myeloperoxidase (MPO) activity, nitrite/nitrate (N/N) concentration, lipid peroxidation, protein carbonyls formation, superoxide dismutase (SOD) and catalase (CAT) activity were determined in the prefrontal cortex, hippocampus, cortex, cerebellum and striatum. Results: After I/R, MPO activity increased in the prefrontal cortex, hippocampus, cortex and cerebellum and N/N concentration elevated in the prefrontal cortex, hippocampus and cortex, while MCC950 decreased this level except in hippocampus. After I/R, lipid peroxidation enhanced in the prefrontal cortex and cerebellum and increased the oxidative protein damage in both structures and hippocampus. MCC950 decreased lipid peroxidation in the prefrontal cortex and decreased protein oxidative damage in all brain structures except in the striatum. SOD activity decreased in the cortex after I/R and MCC950 reestablished these levels. CAT activity decreased in the prefrontal cortex, hippocampus and cerebellum after I/R and MCC950 reestablished these levels in the prefrontal cortex.Conclusion: Our data provide novel demonstration that inhibiting NLRP3 activation with MCC950 reduces brain oxidative damage after cerebral I/R in rats.

Hyperoxia by short-term promotes oxidative damage and mitochondrial dysfunction in rat brain.

Oxygen (O2) therapy is used as a therapeutic protocol to prevent or treat hypoxia. However, a high inspired fraction of O2 (FIO2) promotes hyperoxia, a harmful condition for the central nervous system (CNS). The present study evaluated parameters of oxidative stress and mitochondrial dysfunction in the brain of rats exposed to different FIO2. Male Wistar rats were exposed to hyperoxia (FIO2 40 % and 60 %) compared to the control group (FIO2 21 %) for 2 h. Oxidative stress, neutrophilic infiltration, and mitochondrial respiratory chain enzymes were determined in the hippocampus, striatum, cerebellum, cortex, and prefrontal cortex after O2 exposure. The animals exposed to hyperoxia showed increased lipid peroxidation, formation of carbonyl proteins, N/N concentration, and neutrophilic infiltration in some brain regions, like hippocampus, striatum, and cerebellum being the most affected. Furthermore, CAT activity and activity of mitochondrial enzyme complexes were also altered after exposure to hyperoxia. Rats exposed to hyperoxia showed increase in oxidative stress parameters and mitochondrial dysfunction in brain structures.

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.

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.

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.

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.

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.

Omega-3 polyunsaturated fatty acids have beneficial effects on visceral fat in diet-induced obesity model.

This study evaluated the effects of omega-3 polyunsaturated fatty acids (PUFAs) on oxidative stress and energy metabolism parameters in the visceral fat of a high-fat-diet induced obesity model. Energy intake, body mass, and visceral fat mass were also evaluated. Male Swiss mice received either a control diet (control group) or a high-fat diet (obese group) for 6 weeks. After this period, the groups were divided into control + saline, control + omega-3, obese + saline, and obese + omega-3, and to these groups 400 mg·(kg body mass)-1·day-1 of fish oil (or saline) was administered orally, for 4 weeks. Energy intake and body mass were monitored throughout the experiment. In the 10th week, the animals were euthanized and the visceral fat (mesenteric) was removed. Treatment with omega-3 PUFAs did not affect energy intake or body mass, but it did reduced visceral fat mass. In visceral fat, omega-3 PUFAs reduced oxidative damage and alleviated changes to the antioxidant defense system and the Krebs cycle. The mitochondrial respiratory chain was neither altered by obesity nor by omega-3 PUFAs. In conclusion, omega-3 PUFAs have beneficial effects on the visceral fat of obese mice because they mitigate changes caused by the consumption of a high-fat diet.

Oxidative stress and mitochondrial dysfunction contributes to postoperative cognitive dysfunction in elderly rats.

Postoperative cognitive dysfunction (POCD) is defined by cognitive impairment determined by neuropsychological tests from before to after surgery. Several mechanisms have been proposed in this bidirectional communication between the immune system and the brain after surgery. We aimed at understanding the mechanisms underlying POCD elderly rats in an experimental tibial fracture model. Elderly male Wistar rats were subjected to tibial fracture (TF) model. Control (sham) and fracture (TF) groups were followed to determine nitrite/nitrate concentration; oxidative damage to lipids and proteins; the activity of antioxidant enzymes (superoxide dismutase-SOD and catalase-CAT), mitochondrial respiratory chain enzymes, and creatine kinase (CK); and BDNF levels in the hippocampus and prefrontal cortex (at 24 h and at seven days) and cognitive function through habituation to the open field task and novel object recognition task (only at seven days). TF group presented increased concentration of nitrite/nitrate, hippocampal lipid peroxidation at seven days, protein oxidative damage in the prefrontal cortex and hippocampus at 24 h, decreased antioxidant activity in both structures on the first postoperative day and compromised function of the mitochondrial respiratory chain complexes as well as the CK enzyme. In addition, the levels of BDNF were reduced and memory function was impaired in the TF group. In conclusion, elderly rats submitted to an experimental model of tibial fracture displayed memory impairment accompanied by an increase in oxidative stress, mitochondrial dysfunction and reduced neurotrophin level.

Effects of Different Parameters of Continuous Training and High-Intensity Interval Training in the Chronic Phase of a Mouse Model of Complex Regional Pain Syndrome Type I.

This study evaluated the effects of continuous and interval running on a treadmill on mechanical hyperalgesia in an animal model of chronic postischemia pain and analyzed the mechanism of action of this effect. Different groups of male Swiss mice with chronic postischemia pain, induced by 3 hours of paw ischemia followed by reperfusion, ran on the treadmill in different protocols-the speed (10, 13, 16, or 19 m/min), duration (15, 30, or 60 minutes), weekly frequency (3 or 5 times), weekly increase in continuous and interval running speed-were tested. Mechanical hyperalgesia was evaluated by von Frey filament 7, 14, and 21 days after paw ischemia followed by reperfusion. On day 11 after paw ischemia followed by reperfusion and after 5 days of continuous and interval running, concentrations of cytokines, oxidative stress parameters, and extracellular signal-regulated kinase 1/2 and AKT 1/2/3 expression in the spinal cord were measured. The results showed that continuous running has an antihyperalgesic effect that depends on intensity and volume. Interval running has a longer-lasting antihyperalgesic effect than continuous running. The antihyperalgesic effect depends on intensity and volume in continuous running, and increasing speed maintains the antihyperalgesic effect in both protocols. In the spinal cord, both runs decreased tumor necrosis factor-α and interleukin-6 levels and increased interleukin-10. Both running protocols reduced oxidative damage in the spinal cord. Only interval running had lower concentrations of phosphorylated extracellular signal-regulated kinase 1/2 in the spinal cord. Interval running presented a great antihyperalgesic potential with more promising results than continuous running, which may be owing to the fact that the interval running can activate different mechanisms from those activated by continuous running. PERSPECTIVE: A minimum of .5-hour sessions of moderate to high intensity ≥3 times a week are essential parameters for continuous and interval running-induced analgesia. However, interval running was shown to be more effective than continuous running and can be an important adjuvant treatment to chronic pain.

Dimethyl Fumarate Limits Neuroinflammation and Oxidative Stress and Improves Cognitive Impairment After Polymicrobial Sepsis.

Sepsis is caused by a dysregulated host response to infection, often associated with acute central nervous system (CNS) dysfunction, which results in long-term cognitive impairment. Dimethyl fumarate (DMF) is an important agent against inflammatory response and reactive species in CNS disorders. Evaluate the effect of DMF on acute and long-term brain dysfunction after experimental sepsis in rats. Male Wistar rats were submitted to the cecal ligation and puncture (CLP) model. The groups were divided into sham (control) + vehicle, sham + NAC, sham + DMF, CLP + vehicle, CLP + NAC, and CLP + DMF. The animals were treated with DMF (15 mg/kg at 0 and 12 h after CLP, per gavage) and the administration of n-acetylcysteine (NAC) (20 mg/kg; 3, 6, and 12 h after CLP, subcutaneously) was used as positive control. Twenty-four hours after CLP, cytokines, myeloperoxidase (MPO), nitrite/nitrate (N/N), oxidative damage to lipids and proteins, and antioxidant enzymes were evaluated in the hippocampus, total cortex, and prefrontal cortex. At 10 days after sepsis induction, behavioral tests were performed to assess cognitive damage. We observed an increase in cytokine levels, MPO activity, N/N concentration, and oxidative damage, a reduction in SOD and GPx activity in the brain structures, and cognitive damage in CLP rats. DMF treatment was effective in reversing these parameters. DMF reduces sepsis-induced neuroinflammation, oxidative stress, and cognitive impairment in rats subjected to the CLP model.

Acute treatment with ketamine and chronic treatment with minocycline exert antidepressant-like effects and antioxidant properties in rats subjected different stressful events.

Despite decades of research, the fundamental neurochemical and molecular mechanisms underlying the major depressive disorder (MDD) are still poorly understood, and current antidepressant treatments have limited clinical efficacy. In clinical conditions, the rapprochement between the disease and the corrective actions of drugs in laboratory animals is essential for developing effective therapies. Thus, the aim of this study was to evaluate the antidepressant effects of ketamine (N-metil-d-asparte (NMDA) receptor antagonist), minocycline (tetracycline antibiotic), and amitriptyline (classical antidepressant), on behavior and oxidative stress parameters in animals submitted to the chronic mild stress (CMS) and maternal deprivation protocols. For this aim, male Wistar rats were submitted to maternal deprivation or CMS. To induce maternal deprivation, Wistar rats were deprived of maternal care during the first 10 days of life. To induce CMS, Wistar rats were submitted to the CMS for 40 days. To reverse the effects of stress, treatment was done intraperitoneally with a single dose of ketamine (15 mg/kg), and minocycline (25 mg/kg) and amitriptyline (10 mg/kg) by 20 days. After treatment, the animals were submitted to the forced swimming test and then analyzed oxidative stress parameters in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens (NAc). Treatment with ketamine, minocycline and amitriptyline were able to exert antidepressant effects in the forced swimming test. However, these antidepressant effects were dependent on the stress model by which the animals were exposed. In certain brain regions some treatment strategies had a pro-oxidant effect. Though, most of the strategies used in this study had antioxidant effects, as reported by a decrease on protein and lipid damage, nitrite/nitrate concentration and myeloperoxidase activity. In addition, an increase in the antioxidant superoxide dismutase (SOD) and catalase (CAT) enzymes activities were also evident after treatments. In conclusion, the antidepressant effects of ketamine and minocycline, in the present study, may be associated, at least in part, with its antioxidant and neuroprotective effects in animals subjected to maternal deprivation or CMS.

Dimethyl Fumarate Modulates Oxidative Stress and Inflammation in Organs After Sepsis in Rats.

Sepsis is defined as life-threatening organ dysfunction induced by a disrupted host response to infecting pathogens. Evidences suggest that oxidative stress is intrinsically related to sepsis progression. Dimethyl fumarate (DMF) is a novel oral therapeutic agent with anti-oxidant properties which exerts protective effects through activation of nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2). Thus, the aim of this study is to evaluate the effect of DMF in different organs of rats submitted to an animal model of sepsis. Adult male Wistar rats were subjected to sepsis by cecal ligation and puncture (CLP) procedure and sham-operated rats was considered control group. The experimental groups were divided into sham + vehicle, sham + DMF, sham + NAC, CLP + vehicle, CLP + DMF, and CLP + NAC. Rats were treated by oral gavage with DMF immediately after and 12 h after surgery, or NAC (s.c.) at 3, 6, and 12 h after surgery. Twenty-four hours after sepsis induction, neutrophil infiltration, nitrite/nitrate concentrations, oxidative damage to lipids and proteins, superoxide dismutase (SOD), and catalase (CAT) activities were evaluated in the heart, liver, lung, and kidney. Septic animals presented increased neutrophil infiltration, NO metabolism, oxidative damage to lipids and proteins, and decreases of SOD and CAT activities, mainly in the heart, liver, and lung, while DMF-treated animals showed significant reduction in neutrophil infiltration, NO metabolism, and oxidative damage followed by increased SOD and CAT activities. DMF is effective in preventing oxidative stress and inflammation in rats 24 h after sepsis induction.

Vitamin B6 Reduces Neurochemical and Long-Term Cognitive Alterations After Polymicrobial Sepsis: Involvement of the Kynurenine Pathway Modulation.

Neurological dysfunction as a result of neuroinflammation has been reported in sepsis and cause high mortality. High levels of cytokines stimulate the formation of neurotoxic metabolites by kynurenine (KYN) pathway. Vitamin B6 (vit B6) has anti-inflammatory and antioxidant properties and also acts as a cofactor for enzymes of the KYN pathway. Thus, by using a relevant animal model of polymicrobial sepsis, we studied the effect of vit B6 on the KYN pathway, acute neurochemical and neuroinflammatory parameters, and cognitive dysfunction in rats. Male Wistar rats (250-300 g) were submitted to cecal ligation and perforation (CLP) and divided into sham + saline, sham + vit B6, CLP + saline, and CLP + vit B6 (600 mg/kg, s.c.) groups. Twenty-four hours later, the prefrontal cortex and hippocampus were removed for neurochemical and neuroinflammatory analyses. Animals were followed for 10 days to determine survival rate, when cognitive function was assessed by behavioral tests. Vitamin B6 interfered in the activation of kynurenine pathway, which led to an improvement in neurochemical and neuroinflammatory parameters and, consequently, in the cognitive functions of septic animals. Thus, the results indicate that vit B6 exerts neuroprotective effects in acute and late consequences after sepsis.