Francieli Guolo

Asthma represents a public health problem and traditionally is classified as an atopic disease, where the allergen can induce clinical airway inflammation, bronchial hyperresponsiveness, and reversible obstruction of airways. Studies have demonstrated the presence of T-helper 2 lymphocytes in the lung of patients with asthma. These cells are involved in cytokine production that regulates immunoglobulin synthesis. Recognizing that T cell interaction with antigens/allergens is key to the development of inflammatory diseases, the aim of this study is to evaluate the anti-inflammatory potential of cannabidiol (CBD) in this setting. Asthma was induced in 8-week-old Wistar rats by ovalbumin (OVA). In the last 2 days of OVA challenge animals received CBD (5 mg/kg, i.p.) and were killed 24 hours after. The levels of IL-4, IL-5, IL-13, IL-6, IL-10, and TNF-αwere determinate in the serum. CBD treatment was able to decrease the serum levels of all analyzed cytokines except for IL-10 levels. CB...

The aim of this study was to determine parameters of NO metabolism in plasma and placenta of preeclamptic (PE) patients. It was conducted a case-control study at São José Hospital, Brazil. Thirty-three PE and 33 normotensive pregnant were included in the study. The diagnosis of PE was established in accordance with the definitions of American College of Obstetricians and Gynecologists. Peripheral venous blood and placenta samples were obtained at postpartum period. Plasma NO levels and SOD activity were significantly lower and endothelin-1 levels and arginase activity were significantly higher in PE women when compared to controls. None of the analyzed parameters were different in the placenta between groups. Our findings suggest that parameters associated with NO metabolism are altered only at the systemic level, but not in placenta of PE patients.

Red blood cell transfusions are common in intensive care units. For many years, transfusions of red blood were thought to have obvious clinical benefits. However, in recent years, the risks and benefits of blood transfusions have been examined more carefully, including the risk of increased morbidity and mortality due to transfusion-related immunomodulation effects. To evaluate red blood cell transfusion effects and the relationship of this procedure to the production of inflammatory cytokines and oxidative damage in critically ill patients admitted to an intensive care unit. For 6 months in 2008, we evaluated patients admitted to an intensive care unit who underwent packed red blood cell transfusions. Pre- and post-transfusion levels of interleukin-6, carbonylated proteins and thiobarbituric acid reactive substances were assessed. Serum post-transfusion interleukin-6 levels were reduced, and thiobarbituric acid reactive substances and carbonylated proteins were significantly increa...

Major depression is characterized for symptoms at the psychological, behavioral and physiological levels. The chronic mild stress model has been used as an animal model of depression. The consumption of sweet food, locomotor activity, body weight, lipid and protein oxidation levels and superoxide dismutase and catalase activities in the rat hippocampus, prefrontal cortex and cortex were assessed in rats exposed

There is no description on the mechanisms associated with blood-brain barrier (BBB) disruption during sepsis development. Thus, we here determined changes in permeability of the BBB in an animal model of severe sepsis and the role of matrix metalloproteinase (MMP)-2 and MMP-9 in the dysfunction of the BBB. Sepsis was induced in Wistar rats by cecal ligation and perforation. BBB permeability was assessed using the Evans blue dye method. The content of MMP-2 and MMP-9 in the cerebral microvessels was determined by western blot. The activity of MMP-2 and MMP-9 was determined using zymography. An inhibitor of MMP-2 and MMP-9 or specific inhibitors of MMP-2 or MMP-9 were administered to define the role of MMPs on BBB permeability, brain inflammatory response, and sepsis-induced cognitive alterations. The increase of BBB permeability is time-related to the increase of MMP-9 and MMP-2 in the microvessels, both in cortex and hippocampus. Using an MMP-2 and MMP-9 inhibitor, or specific MMP-2 or MMP-9 inhibitors, the increase in the permeability of the BBB was reversed. This was associated with lower brain levels of interleukin (IL)-6 and lower oxidative damage. In contrast, only the inhibition of both MMP-9 and MMP-2 was able to improve acute cognitive alterations associated with sepsis. In conclusion, MMP-2 and MMP-9 activation seems to be a major step in BBB dysfunction, but BBB dysfunction seems not to be associated with acute cognitive dysfunction during sepsis development.

Oxidative stress and inflammation is likely to be a major step in the development of sepsis-associated encephalopathy (SAE) and long-term cognitive impairment. To date, it is not known whether brain inflammation and oxidative damage are a direct consequence of systemic inflammation or whether these events are driven by brain resident cells, such as microglia. Therefore, the aim of this study is to evaluate the effect of minocycline on behavioral and neuroinflammatory parameters in rats submitted to sepsis. Male Wistar rats were subjected to sepsis by cecal ligation and puncture (CLP). The animals were divided into sham-operated (Sham+control), sham-operated plus minocycline (sham+MIN), CLP (CLP+control) and CLP plus minocycline (CLP+MIN) (100 μg/kg, administered as a single intracerebroventricular (ICV) injection). Some animals were killed 24h after surgery to assess the breakdown of the blood brain barrier, cytokine levels, oxidative damage to lipids (TBARS) and proteins in the hippocampus. Some animals were allowed to recover for 10 days when step-down inhibitory avoidance and open-field tasks were performed. Treatment with minocycline prevented an increase in markers of oxidative damage and inflammation in the hippocampus after sepsis. This was associated with an improvement in long-term cognitive performance. In conclusion, we demonstrated that the inhibition of the microglia by an ICV injection of minocycline was able to decrease acute brain oxidative damage and inflammation as well as long-term cognitive impairment in sepsis survivors.

A growing body of evidence points toward an association between the glutamatergic system, as well as immune system dysregulation and major depression. So, the present study was aimed at evaluating the behavioral and molecular effects of the ketamine, an antagonist of the N-methyl-d-aspartate (NMDA) receptor of glutamate in maternally deprived adult rats. In deprived rats treated with saline, we observed an increase in the immobility time; however, ketamine treatment reversed this effect, decreasing immobility time. In addition, maternal deprivation induced an increase in cytokines: TNF-α and IL-1in serum, and in IL-6 in serum and cerebrospinal fluid (CSF). Interestingly, ketamine treatment reduced the levels of all the cytokines in deprived rats. In conclusion, these findings further support a relationship between immune activation and depression. Considering the action of ketamine, this study suggested that antagonists of the NMDA receptor, such as ketamine, could exert their effec...

Animal models of chronic stress represent valuable tools by which to investigate the behavioral, endocrine and neurobiological changes underlying stress-related psychopathologies, such as major depression, and the efficacy of antidepressant therapies. The present study was aimed at investigating the neurochemical effects of the antidepressant tianeptine in rats exposed to the chronic stress model. To this aim, rats were subjected to 40days of chronic unpredictable stressful stimuli, after which the animals received saline or tianeptine (15mg/kg) once a day for 7days. Additionally, IL-6, IL-1, TNF-α levels and oxidative stress parameters were assessed in the prefrontal cortex (PFC), hippocampus (HPC), amygdala (AMY) and nucleus accumbens (NAc) in all of the experimental groups studied. The results indicated that chronic mild stress and tianeptine did not exercise any effects on cytokines in all of the structures studied; in the PFC and AMY thiobarbituric acid reactive substances (TBARS) levels were decreased in control rats treated with tianeptine in the HPC; superoxide dismutase (SOD) activity was found to have decreased in stressed rats treated with saline in the PFC, HPC, AMY and NAc, and tianeptine reversed this effect; catalase (CAT) activity was found to have decreased in the PFC, HPC and NAc of stressed rats treated with saline, but was shown to have increased in stressed rats treated with tianeptine, and tianeptine also reversed the decreases in CAT activity in stressed rats treated with saline, suggesting that tianeptine exerted antioxidant activity. In conclusion, the present findings open new vistas on the pharmacological activity of tianeptine, in particular, concerning its ability to attenuate oxidative stress.

Bacterial meningitis is associated with intense inflammation and also linked to the production of reactive oxygen species. To this aim, animals underwent a magna cistern tap and received either sterile saline as a placebo or an equivalent volume of a Streptococcus pneumoniae suspension. The animals began antibiotic therapy 16h after induction. The animals were sacrificed at 24 or 48h post-infection and the hippocampus and cortex were harvested. The activity of the enzymes superoxide dismutase, catalase, and thiobarbituric acid reactive species, protein carbonyls, and free sulphydryl groups were altered, but reversed, in part, by the antibiotic treatment. Our results support the hypothesis that antibiotic treatment prevents, in part, the oxidative stress in the bacterial meningitis induced by Streptococcus pneumoniae.

The derangement in oxygen utilization occurring during sepsis is likely to be linked to impaired mitochondrial functioning. Skeletal muscle comprises 50%-60% of body cell mass and represents the largest organ potentially affected by systemic inflammation. Thus, we investigated whether sepsis induced by cecal ligation and puncture (CLP) modifies mitochondrial activity in respiratory and nonrespiratory skeletal muscle.

Sepsis is characterized by systemic biochemical alterations including the central nervous system in the early times and cognitive impairment at later times after sepsis induction in the animal model. Recent studies have shown that, besides its hematological activity, erythropoietin (EPO) has cytoprotective effects on various cells and tissues. In order to corroborate elucidating the effects of alternative drugs for sepsis treatment, we evaluated the effects of both acute and chronic EPO treatment on oxidative stress and energetic metabolism in the hippocampus, and cognitive impairment, respectively, after sepsis induction by cecal ligation and perforation (CLP). To this aim, male Wistar rats underwent CLP with "basic support" or sham operation. In the acute treatment, EPO was administered once immediately after CLP induction. The rats were then killed after 6 and 24 h, and the hippocampus was removed for analysis of oxidative stress and energetic metabolism, respectively. Regarding the chronic treatment, EPO was administered once daily until the 4th day after induction. Aversive memory was tested on the 10th day after surgery. It was observed that the acute use of EPO (a single dose) alters the oxidative parameters and energetic metabolism. Chronic use (4 days) reversed cognitive impairment in the sepsis animal model. Mortality rates were attenuated only during chronic treatment.

Pneumococcal meningitis is associated with neurologic sequelae, such as learning and memory impairment. Most recently, a nonbacteriolytic antibiotic has been investigated to minimise the inflammatory host response and prevent cognitive damage. In this study, we compared daptomycin (DPTO) or ceftriaxone (CFX) treatment on the inflammatory parameters and on the blood-brain barrier (BBB) integrity in experimental pneumococcal meningitis. In the first experiment, the animals received 10 µl of a Streptococcus pneumoniae suspension or artificial cerebrospinal fluid by intracerebroventricular (i.c.v.) and were treated with CFX or DPTO at 18 h post-infection. The animals were euthanised at 18, 20, 24, 36 and 40 h post-infection. In the hippocampus, brain-derived neurotrophic factor (BDNF), tumour necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and IL-10 levels were not different between treatment groups; however, IL-4 and cytokine-induced neutrophil chemoattractant 1 (CINC-1) levels decreased in the CFX group. In the frontal cortex, TNF-α, IL- 4, IL-6, IL-10 and BDNF levels were not different between treatment groups. Only CINC-1 levels decreased at 40 h postinfection with CFX treatment. In the second experiment, the animals received DPTO or CFX for 7 days and were euthanised 10 days after pneumococcal meningitis induction. TNF-α, IL-6, IL-10, CINC-1 and BDNF levels were not different between treatment groups in the hippocampus; however, IL-4 levels decreased in CFX group. In the third experiment, the animals received 10 µl of an S. pneumoniae suspension or artificial CSF by i.c.v. and were treated with a single dose of CFX or DTPO antibiotic; assessment of the BBB breakdown showed that both antibiotics prevented the BBB disruption. Both treatments equally protected the BBB integrity, and there were no significant difference in cytokine production.