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.

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.

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.

Diabetes Exacerbates Sepsis-Induced Neuroinflammation and Brain Mitochondrial Dysfunction.

Sepsis is a life-threatening organ dysfunction, which demands notable attention for its treatment, especially in view of the involvement of immunodepressed patients, as the case of patients with diabetes mellitus (DM), who constitute a population susceptible to develop infections. Thus, considering this endocrine pathology as an implicatory role on the immune system, the aim of this study was to show the relationship between this disease and sepsis on neuroinflammatory and neurochemical parameters. Levels of IL-6, IL-10, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and mitochondrial respiratory chain complexes were evaluated in the hippocampus and prefrontal cortex 24 h after sepsis by cecal ligation and perforation (CLP) in Wistar rats induced to type 1 diabetes by alloxan (150 mg/kg). It was verified that diabetes implied immune function after 24 h of sepsis, since it contributed to the increase of the inflammatory process with higher production of IL-6 and decreased levels of IL-10 only in the hippocampus. In the same brain area, a several decrease in NGF level and activity of complexes I and II of the mitochondrial respiratory chain were observed. Thus, diabetes exacerbates neuroinflammation and results in mitochondrial impairment and downregulation of NGF level in the hippocampus after sepsis.

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.