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3.
Int J Neurosci ; 133(4): 375-388, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33902404

RESUMO

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.


Assuntos
Lesões Encefálicas , Isquemia Encefálica , Ataque Isquêmico Transitório , Ratos , Masculino , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos Wistar , Encéfalo/metabolismo , Estresse Oxidativo , Antioxidantes/metabolismo , Lesões Encefálicas/metabolismo , Superóxido Dismutase/metabolismo
4.
Neuroimmunomodulation ; 29(4): 269-281, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36323239

RESUMO

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.


Assuntos
COVID-19 , Humanos , COVID-19/complicações , Peptidil Dipeptidase A/metabolismo , Pulmão/metabolismo , Encéfalo/metabolismo , Cognição
6.
Neurochem Int ; 135: 104712, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32126248

RESUMO

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.


Assuntos
Encéfalo/imunologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Neuroimunomodulação/imunologia , Neuroproteção/imunologia , Sepse/imunologia , Fatores Etários , Animais , Encéfalo/efeitos dos fármacos , Masculino , Neuroimunomodulação/efeitos dos fármacos , Neuroproteção/efeitos dos fármacos , Ratos , Ratos Wistar , Sepse/induzido quimicamente
7.
Inflammation ; 43(3): 1019-1034, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31981061

RESUMO

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.


Assuntos
Coinfecção/metabolismo , Modelos Animais de Doenças , Comportamento de Doença/fisiologia , Mediadores da Inflamação/metabolismo , Locomoção/fisiologia , Sepse/metabolismo , Animais , Coinfecção/psicologia , Ingestão de Alimentos/fisiologia , Ingestão de Alimentos/psicologia , Inflamação/metabolismo , Inflamação/psicologia , Masculino , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Sepse/psicologia
8.
J Drug Target ; 28(4): 428-436, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31594390

RESUMO

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.


Assuntos
Acetilcisteína/metabolismo , Ouro/farmacologia , Nanopartículas Metálicas/administração & dosagem , Sepse/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Ratos , Ratos Wistar , Sepse/metabolismo
9.
Microvasc Res ; 128: 103956, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31733304

RESUMO

Blood brain barrier (BBB) permeability and oxidative stress have been reported to be important mechanisms for brain damage following ischemic stroke and stanniocalcin-1 (STC-1), a neuroprotective protein, has anti-inflammatory and anti-oxidative stress properties. Herein, we report the effect of STC-1 on BBB permeability and brain oxidative stress after stroke in an animal model. Male Wistar received an intracerebroventricularly injection of human recombinant STC-1 (100 ng/kg) or saline and were subjected to sham procedure or global cerebral ischemia/reperfusion (I/R) model. Six and 24 h after I/R, neurological evaluation was performed; at 24 h brain water content was evaluated in the total brain, and BBB permeability, nitrite/nitrate (N/N) concentration, lipid peroxidation, protein carbonyls formation, superoxide dismutase (SOD) and catalase (CAT) activity were determined in the hippocampus, cortex, prefrontal cortex, striatum and cerebellum. Rats exhibited neurological deficit at 6 and 24 h after I/R and STC-1 reduction at 24 h. After I/R there were an increase of brain water content, BBB permeability in the hippocampus, cortex and pre-frontal cortex and N/N in the hippocampus, and STC-1 decreased this level only in the hippocampus. STC-1 decreased lipid peroxidation in the hippocampus, cortex and prefrontal cortex and protein oxidative damage in the hippocampus and cortex. SOD activity decreased in the hippocampus, cortex and prefrontal cortex after I/R and STC-1 reestablished these levels in the hippocampus and cortex. CAT activity decreased only in the hippocampus and cortex and STC-1 increased the CAT activity in the hippocampus. Our data provide the first experimental demonstration that STC-1 reduced brain dysfunction associated with cerebral I/R in rats, by decreasing BBB permeability and oxidative stress parameters.


Assuntos
Antioxidantes/administração & dosagem , Isquemia Encefálica/prevenção & controle , Encéfalo/efeitos dos fármacos , Permeabilidade Capilar/efeitos dos fármacos , Glicoproteínas/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/fisiopatologia , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Edema Encefálico/metabolismo , Edema Encefálico/fisiopatologia , Edema Encefálico/prevenção & controle , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatologia , Modelos Animais de Doenças , Injeções Intraventriculares , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Carbonilação Proteica/efeitos dos fármacos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Transdução de Sinais
10.
Nutrition ; 70: 110417, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30867119

RESUMO

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.


Assuntos
Anti-Inflamatórios/farmacologia , Disfunção Cognitiva/prevenção & controle , Óleos de Peixe/farmacocinética , Estresse Oxidativo/efeitos dos fármacos , Sepse/psicologia , Animais , Biomarcadores/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Doenças do Ceco/complicações , Doenças do Ceco/microbiologia , Ceco/irrigação sanguínea , Ceco/microbiologia , Disfunção Cognitiva/microbiologia , Modelos Animais de Doenças , Emulsões , Lobo Frontal/efeitos dos fármacos , Interleucina-1beta/metabolismo , Perfuração Intestinal/complicações , Perfuração Intestinal/microbiologia , Ligadura/efeitos adversos , Masculino , Permeabilidade , Carbonilação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar , Sepse/etiologia , Sepse/microbiologia
11.
Curr Protoc Immunol ; 126(1): e83, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31483106

RESUMO

The blood-brain barrier (BBB) is an active and selective barrier that shields the brain from endogenous and exogenous insults. Different stimuli may lead to the disruption of this barrier, including inflammation and trauma. Several methods are used to evaluate BBB disruption. The most widely used method is Evans blue (EB) dye extravasation. EB cannot normally pass through the BBB and thus its presence in brain tissue indicates alterations in permeability. This protocol details the steps of EB extravasation in rodents. Important aspects regarding critical steps and advantages are also provided. © 2019 by John Wiley & Sons, Inc.


Assuntos
Barreira Hematoencefálica/patologia , Lesões Encefálicas Traumáticas/patologia , Encéfalo/patologia , Azul Evans/metabolismo , Inflamação/patologia , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Camundongos , Ratos
12.
Neurochem Int ; 108: 436-447, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28606823

RESUMO

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 α-lipoic acid (ALA) effect as an important antioxidant compound on brain dysfunction in rats. Wistar rats were subjected to sepsis by cecal ligation and perforation (CLP) or sham (control) and treated orally with ALA (200 mg/kg after CLP) or vehicle. Animals were divided into sham + saline, sham + ALA, CLP + saline and CLP + ALA groups. Twelve, 24 h and 10 days after surgery, the hippocampus, prefrontal cortex and cortex were obtained and assayed for levels of TNF-α and IL-1ß, blood brain barrier (BBB) permeability, nitrite/nitrate concentration, myeloperoxidase (MPO) activity, thiobarbituric acid reactive species (TBARS) formation, protein carbonyls, superoxide dismutase (SOD) and catalase (CAT) activity and neurotrophins levels. Behavioral tasks were performed 10 days after surgery. ALA reduced BBB permeability and TNF-α levels in hippocampus in 24 h and IL-1ß levels and MPO activity in hippocampus and prefrontal cortex in 24 h. ALA reduced nitrite/nitrate concentration and lipid peroxidation in 24 h in all structures and protein carbonylation in 12 and 24 h in hippocampus and cortex. CAT activity increased in the hippocampus and cortex in all times. ALA enhanced NGF levels in hippocampus and cortex and prevented cognitive impairment. Our data demonstrates that ALA reduces the consequences of polymicrobial sepsis in rats by decreasing inflammatory and oxidative stress parameters in the brain.


Assuntos
Antioxidantes/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Coinfecção/tratamento farmacológico , Mediadores da Inflamação/antagonistas & inibidores , Sepse/tratamento farmacológico , Ácido Tióctico/uso terapêutico , Doença Aguda , Animais , Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Coinfecção/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Sepse/metabolismo , Ácido Tióctico/farmacologia , Fatores de Tempo
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