RESUMO
The pathophysiology of post-traumatic brain injury (TBI) behavioral and cognitive changes is not fully understood, especially in its mild presentation. We designed a weight drop TBI model in mice to investigate the role of neuroinflammation in behavioral and cognitive sequelae following mild TBI. C57BL/6 mice displayed depressive-like behavior at 72 h after mild TBI compared with controls, as indicated by a decrease in the latency to first immobility and climbing time in the forced swim test. Additionally, anxiety-like behavior and hippocampal-associated spatial learning and memory impairment were found in the elevated plus maze and in the Barnes maze, respectively. Levels of a set of inflammatory mediators and neurotrophic factors were analyzed at 6 h, 24 h, 72 h, and 30 days after injury in ipsilateral and contralateral hemispheres of the prefrontal cortex and hippocampus. Principal components analysis revealed two principal components (PC), which represented 59.1% of data variability. PC1 (cytokines and chemokines) expression varied between both hemispheres, while PC2 (neurotrophic factors) expression varied only across the investigated brain areas. Our model reproduces mild TBI-associated clinical signs and pathological features and might be a valuable tool to broaden the knowledge regarding mild TBI pathophysiology as well as to test potential therapeutic targets.
Assuntos
Concussão Encefálica , Lesões Encefálicas Traumáticas , Camundongos , Animais , Concussão Encefálica/complicações , Camundongos Endogâmicos C57BL , Encéfalo/patologia , Lesões Encefálicas Traumáticas/complicações , Fatores de Crescimento Neural , Cognição , Aprendizagem em Labirinto/fisiologia , Modelos Animais de DoençasRESUMO
PURPOSE: To evaluate a biofilm model of Pseudomonas aeruginosa in excisional cutaneous wound in mice. METHODS: Preclinical, translational study conducted with 64 C57BL/6 mice randomly assigned to control and intervention groups. Evaluation was on days D0, D3, D5, D7 and D10 of wound making. The profile of biofilm formation and induction was evaluated using wound closure kinetics, quantitative culture, and evaluation of wounds using transmission electron microscopy (TEM). Clinical evaluation was performed by liver tissue culture, weight variation, and quantification of leukocytes in peripheral blood. Analyses were performed with GraphPad Prism software. RESULTS: Bacterial load for induction of infection with P. aeruginosa and survival of animals was 104 UFC·mL-1. In D5 (p < 0.0001) and D7 (p < 0.01), animals in the intervention group showed a delay in the healing process and had their wounds covered by necrotic tissue until D10. Statistical differences were observed in wound cultures and weight at D5 and D7 (p < 0.01). Liver cultures and leukocyte quantification showed no statistical differences. No bacteria in planktonic or biofilm form were identified by TEM. CONCLUSIONS: The findings raise questions about the understanding of the ease of formation and high occurrence of biofilm in chronic wounds.
Assuntos
Infecções por Pseudomonas , Infecção dos Ferimentos , Animais , Camundongos , Biofilmes , Camundongos Endogâmicos C57BL , Pseudomonas aeruginosa , Infecções por Pseudomonas/microbiologia , Infecção dos Ferimentos/microbiologiaRESUMO
Purpose: To evaluate a biofilm model of Pseudomonas aeruginosa in excisional cutaneous wound in mice. Methods: Preclinical, translational study conducted with 64 C57BL/6 mice randomly assigned to control and intervention groups. Evaluation was on days D0, D3, D5, D7 and D10 of wound making. The profile of biofilm formation and induction was evaluated using wound closure kinetics, quantitative culture, and evaluation of wounds using transmission electron microscopy (TEM). Clinical evaluation was performed by liver tissue culture, weight variation, and quantification of leukocytes in peripheral blood. Analyses were performed with GraphPad Prism software. Results: Bacterial load for induction of infection with P. aeruginosa and survival of animals was 104 UFC·mL-1. In D5 (p < 0.0001) and D7 (p < 0.01), animals in the intervention group showed a delay in the healing process and had their wounds covered by necrotic tissue until D10. Statistical differences were observed in wound cultures and weight at D5 and D7 (p < 0.01). Liver cultures and leukocyte quantification showed no statistical differences. No bacteria in planktonic or biofilm form were identified by TEM. Conclusions: The findings raise questions about the understanding of the ease of formation and high occurrence of biofilm in chronic wounds.
Assuntos
Animais , Ratos , Pseudomonas aeruginosa , Cicatrização , Ferimentos e Lesões , Biofilmes , InfecçõesRESUMO
Objetivo:validar método de fixação de curativos em feridas cutâneas excisionais de camundongos. Método: estudo pré-clínico. Amostra composta por animais da linhagem C57BL/6, que tiveram duas feridas excisionais confeccionadas na região dorsal. Foram avaliados diferentes métodos e produtos, amplamente aceitos na prática clínica, para fixação de curativos no modelo animal. Os desfechos avaliados foram tempo de permanência do curativo e ocorrência de eventos adversos. Resultados: atadura de crepom, fita microporosa e bandagem autoaderente apresentaram menor tempo de permanência quando comparadas ao filme de poliuretano. Esse, por sua vez, variou o tempo quando comparadas diferentes marcas (E, F, G e H) e número de voltas ao redor do corpo do animal. Com 1 volta, o tempo variou de < 24 a 36 horas. Com 2 voltas, as marcas E e G permaneceram 48 e 96 horas, respectivamente, e F e H tempo < 24 horas. Filme da marca G, cortado no tamanho 3 cm x 15 cm, dando 2 voltas no corpo do camundongo, manteve o curativo por 96 horas. A pele permaneceu íntegra, sem evento adverso. Conclusão: foi criado modelo de fixação de curativos para feridas em camundongos com produto disponível no Brasil e compatível com a estrutura copórea do animal.
Objective:validate method of fixation of dressings on excisional cutaneous wounds of mice. Method: preclinical study. Sample made up of animals of the C57BL/6 strain, which had two excision wounds made in the dorsal region. Different methods and products, widely accepted in clinical practice, for fixing dressings in the animal model were evaluated. The evaluated outcomes were the length of stay of the dressing and the occurrence of adverse events. Results: crepe bandage, microporous tape and self-adhesive bandage had a shorter residence time when compared to polyurethane film. This, in turn, varied the time when comparing different marks (E, F, G and H) and number of turns around the animal's body. With 1 lap, the time varied from <24 to 36 hours. With 2 laps, the marks E and G remained 48 and 96 hours, respectively, and F and H time <24 hours. G-brand film, cut to size 3 cm x 15 cm, giving the mouse body 2 turns, kept the dressing for 96 hours. The skin remained intact, with no adverse event. Conclusion: a dressing fixation model for wounds in mice was created with a product available in Brazil and compatible with the animal's body structure
Objetivo:validar método de fijación de apósitos en heridas cutáneas excisionales de ratones. Método: estudio preclínico. Muestra compuesta por animales del linaje C57BL/6 que tuvieron dos heridas excisionales confeccionadas en la región dorsal. Se evaluaron distintos métodos y productos, ampliamente aceptados en la práctica clínica, para fijación de apósitos en el modelo animal. Los resultados evaluados fueron tiempo de permanencia del apósito y ocurrencia de eventos adversos. Resultados: La venda de crepé, la cinta microporosa y el vendaje autoadherente presentaron menor tiempo de permanencia cuando comparados con la película de poliuretano. Esta, a su vez, varió en el tiempo cuando comparadas distintas marcas (E, F, G y H) y número de vueltas alrededor del cuerpo del animal. Con una vuelta completa, el tiempo varió de menos de 24 a 36 horas. Con dos vueltas, las marcas E y G permanecieron 48 y 96 horas, respectivamente, y F y H, tiempo igual e inferior a 24 horas. La piel permaneció íntegra, sin evento adverso. Conclusión: se creó un modelo de fijación de apósitos en ratones con un producto disponible en Brasil y compatible con la estructura del cuerpo del animal
Assuntos
Bandagens , Cicatrização , Pesquisa BásicaRESUMO
Sclareol is a bioactive hydrophobic diterpene in the essential oil isolated from Salvia sclarea (Fam. Lamiaceae). Sclareol has been widely studied due to its anti-inflammatory and antioxidant effects. AIMS: The present study aimed to evaluate the effects of Sclareol in different formulations (solid lipid nanoparticle and free) on the metabolic profile of obese mice. MAIN METHODS: Swiss male mice were randomly divided into two groups: standard diet (STD) and high-fat diet (HFD). After obesity induction, each group was divided into three treatment groups: free Sclareol (Sc), Sclareol-loaded lipid nanoparticle (L-Sc) and blank lipid nanoparticle (L). Treatments were performed every day during 30â¯days. KEY FINDINGS: L-Sc improves obese mice metabolic profile by decreasing adiposity, ameliorating insulin sensitivity, glucose tolerance and increasing the HDL plasma levels. In addition, L-Sc decreased the expression of NF-KB, MCP-1 and SERBP-1. SIGNIFICANCE: The use of sclareol together with lipid nanocarriers may be promising for the treatment of metabolic disorders by reducing adipose tissue.
Assuntos
Diterpenos/farmacologia , Intolerância à Glucose/metabolismo , Lipídeos/química , Metaboloma , Nanopartículas/administração & dosagem , Obesidade/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Intolerância à Glucose/tratamento farmacológico , Intolerância à Glucose/etiologia , Masculino , Camundongos , Camundongos Obesos , Nanopartículas/química , Obesidade/tratamento farmacológico , Obesidade/etiologiaRESUMO
PURPOSE: To investigated the inflammatory, angiogenic and fibrogenic activities of the Schinus terebinthifolius Raddi leaves oil (STRO) on wound healing. METHODS: The excisional wound healing model was used to evaluate the effects of STRO. The mice were divided into two groups: Control, subjected to vehicle solution (ointment lanolin/vaseline base), or STRO- treated group, administered topically once a day for 3, 7 and 14 days post-excision. We evaluated the macroscopic wound closure rate; the inflammation was evaluated by leukocytes accumulation and cytokine levels in the wounds. The accumulation of neutrophil and macrophages in the wounds were determined by assaying myeloperoxidase and N-acetyl-ß-D-glucosaminidase activities. The levels of TNF-α, CXCL-1 and CCL-2 in wound were evaluated by ELISA assay. Angiogenesis and collagen fibers deposition were evaluated histologically. RESULTS: We observed that macroscopic wound closure rate was improved in wounds from STRO-group than Control-group. The wounds treated with STRO promoted a reduction in leucocyte accumulation and in pro-inflammatory cytokine. Moreover, STRO treatment increased significantly the number of blood vessels and collagen fibers deposition, as compared to control group. CONCLUSION: Topical application of STRO display anti-inflammatory and angiogenic effects, as well as improvement in collagen replacement, suggesting a putative use of this herb for the development of phytomedicines to treat inflammatory diseases, including wound healing.
Assuntos
Anacardiaceae/química , Indutores da Angiogênese/uso terapêutico , Inflamação/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Óleos de Plantas/uso terapêutico , Cicatrização/efeitos dos fármacos , Animais , Colágeno/análise , Imuno-Histoquímica , Masculino , Camundongos , Folhas de Planta/química , Tela Subcutânea/efeitos dos fármacos , Tela Subcutânea/patologia , Fatores de TempoRESUMO
Abstract Purpose: To investigated the inflammatory, angiogenic and fibrogenic activities of the Schinus terebinthifolius Raddi leaves oil (STRO) on wound healing. Methods: The excisional wound healing model was used to evaluate the effects of STRO. The mice were divided into two groups: Control, subjected to vehicle solution (ointment lanolin/vaseline base), or STRO- treated group, administered topically once a day for 3, 7 and 14 days post-excision. We evaluated the macroscopic wound closure rate; the inflammation was evaluated by leukocytes accumulation and cytokine levels in the wounds. The accumulation of neutrophil and macrophages in the wounds were determined by assaying myeloperoxidase and N-acetyl-β-D-glucosaminidase activities. The levels of TNF-α, CXCL-1 and CCL-2 in wound were evaluated by ELISA assay. Angiogenesis and collagen fibers deposition were evaluated histologically. Results: We observed that macroscopic wound closure rate was improved in wounds from STRO-group than Control-group. The wounds treated with STRO promoted a reduction in leucocyte accumulation and in pro-inflammatory cytokine. Moreover, STRO treatment increased significantly the number of blood vessels and collagen fibers deposition, as compared to control group. Conclusion: Topical application of STRO display anti-inflammatory and angiogenic effects, as well as improvement in collagen replacement, suggesting a putative use of this herb for the development of phytomedicines to treat inflammatory diseases, including wound healing.
Assuntos
Animais , Masculino , Ratos , Cicatrização/efeitos dos fármacos , Óleos de Plantas/uso terapêutico , Extratos Vegetais/uso terapêutico , Anacardiaceae/química , Indutores da Angiogênese/uso terapêutico , Inflamação/tratamento farmacológico , Fatores de Tempo , Imuno-Histoquímica , Colágeno/análise , Folhas de Planta/química , Tela Subcutânea/efeitos dos fármacos , Tela Subcutânea/patologiaRESUMO
Purpose: To investigated the inflammatory, angiogenic and fibrogenic activities of the Schinus terebinthifolius Raddi leaves oil (STRO) on wound healing. Methods: The excisional wound healing model was used to evaluate the effects of STRO. The mice were divided into two groups: Control, subjected to vehicle solution (ointment lanolin/vaseline base), or STRO- treated group, administered topically once a day for 3, 7 and 14 days post-excision. We evaluated the macroscopic wound closure rate; the inflammation was evaluated by leukocytes accumulation and cytokine levels in the wounds. The accumulation of neutrophil and macrophages in the wounds were determined by assaying myeloperoxidase and N-acetyl--D-glucosaminidase activities. The levels of TNF-, CXCL-1 and CCL-2 in wound were evaluated by ELISA assay. Angiogenesis and collagen fibers deposition were evaluated histologically. Results: We observed that macroscopic wound closure rate was improved in wounds from STRO-group than Control-group. The wounds treated with STRO promoted a reduction in leucocyte accumulation and in pro-inflammatory cytokine. Moreover, STRO treatment increased significantly the number of blood vessels and collagen fibers deposition, as compared to control group. Conclusion: Topical application of STRO display anti-inflammatory and angiogenic effects, as well as improvement in collagen replacement, suggesting a putative use of this herb for the development of phytomedicines to treat inflammatory diseases, including wound healing.
Assuntos
Animais , Ratos , Anacardiaceae/química , Anti-Inflamatórios/uso terapêutico , CicatrizaçãoRESUMO
Purpose: To investigated the inflammatory, angiogenic and fibrogenic activities of the Schinus terebinthifolius Raddi leaves oil (STRO) on wound healing. Methods: The excisional wound healing model was used to evaluate the effects of STRO. The mice were divided into two groups: Control, subjected to vehicle solution (ointment lanolin/vaseline base), or STRO- treated group, administered topically once a day for 3, 7 and 14 days post-excision. We evaluated the macroscopic wound closure rate; the inflammation was evaluated by leukocytes accumulation and cytokine levels in the wounds. The accumulation of neutrophil and macrophages in the wounds were determined by assaying myeloperoxidase and N-acetyl--D-glucosaminidase activities. The levels of TNF-, CXCL-1 and CCL-2 in wound were evaluated by ELISA assay. Angiogenesis and collagen fibers deposition were evaluated histologically. Results: We observed that macroscopic wound closure rate was improved in wounds from STRO-group than Control-group. The wounds treated with STRO promoted a reduction in leucocyte accumulation and in pro-inflammatory cytokine. Moreover, STRO treatment increased significantly the number of blood vessels and collagen fibers deposition, as compared to control group. Conclusion: Topical application of STRO display anti-inflammatory and angiogenic effects, as well as improvement in collagen replacement, suggesting a putative use of this herb for the development of phytomedicines to treat inflammatory diseases, including wound healing.(AU)
Assuntos
Animais , Ratos , Anacardiaceae/química , Anti-Inflamatórios/uso terapêutico , CicatrizaçãoRESUMO
Stroke is one of the most frequent causes of death and disability worldwide leading to a significant clinical and socioeconomic burden. Although different mechanisms are involved in the pathogenesis of stroke, inflammatory response occurs after ischemia and contributes to the expansion of brain injury. Platelet-activating factor receptor (PAF) plays crucial roles in both physiological and pathological conditions in the brain. PAF receptor (PAFR) may be expressed on cellular and nuclear membranes of various cell types, especially leukocytes, platelets, endothelial cells, neuronal cells and microglia. Herein, using mice lacking the PAFR receptor (PAFR(-/-)), we investigate a potential role for this receptor during experimental transient global cerebral ischemia and reperfusion (BCCAo). In PAFR deficiency, we observed a significant improvement in the neurological deficits, which were associated with a reduction of brain infarcted area as evaluated by triphenyltetrazolium chloride (TTC). Moreover, a decrease in the percentage of necrotic cavities areas and in the frequency of ischemic neurons was also found by employing histometric analysis. In addition, in PAFR(-/-) mice there was prevention of caspase-3 activation and decreased vascular permeability and brain edema. Decreased brain levels of the cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and the chemokine (C-X-C motif) ligand 1 (CXCL1) by ELISA were also detected in PAFR(-/-) BCCAo animals. Taken together, our results suggest that PAFR activation might be crucial for the global brain ischemia and reperfusion injury.
Assuntos
Ataque Isquêmico Transitório/metabolismo , Glicoproteínas da Membrana de Plaquetas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Barreira Hematoencefálica/fisiopatologia , Infarto Encefálico/etiologia , Caspase 3/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/genética , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Doenças do Sistema Nervoso/etiologia , Glicoproteínas da Membrana de Plaquetas/genética , Receptores Acoplados a Proteínas G/genética , Traumatismo por Reperfusão/patologia , Estatísticas não ParamétricasRESUMO
Acute inflammation and angiogenesis are persistent features of several pathological conditions induced by biological agents leading to the resolution of local and systemic events. Glycoproteins derived from the protozoan Trypanosoma cruzi are suggested to mediate angiogenesis induced by inflammatory cells with still undescribed mechanisms. In this study, we investigated the effects of total antigen from trypomastigote forms of T. cruzi (Y strain), inoculated in sponges 24h after implantation in mice, on angiogenesis, inflammatory cell pattern and endogenous production of inflammatory and angiogenic mediators on days 1, 4, 7 and 14 post-implant. There was an increase in hemoglobin content and in the number of blood vessels associated with T. cruzi antigen stimuli on the 14th day, assessed by the hemoglobin of the implants and by morphometric analysis. However, these antigens were not able to increase type I collagen content on the 14th day. Parasite antigens also induced high production of vascular endothelial growth factor (VEGF) and inflammatory mediators TNF-alpha, CCL2 and CCL5 on the 7th day in sponges when compared to the unstimulated group. Neutrophils and macrophages were determined by measuring myeloperoxidase (MPO) and N-acetyl-ß-d-glucosaminidase (NAG) enzyme activities, respectively. Only NAG was increased after stimulation with antigens, starting from day 4 and peaking at day 7. Together, these data showed that antigens from the Y strain of T. cruzi are able to promote inflammatory neovascularization probably induced by macrophage-induced angiogenic mediators in T. cruzi antigen-stimulated sponges in Swiss mice.
Assuntos
Antígenos de Protozoários/imunologia , Inflamação/imunologia , Inflamação/parasitologia , Neovascularização Patológica , Tampões de Gaze Cirúrgicos , Trypanosoma cruzi/imunologia , Acetilglucosaminidase/metabolismo , Proteínas Angiogênicas/metabolismo , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Feminino , Inflamação/metabolismo , Inflamação/fisiopatologia , Mediadores da Inflamação/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/parasitologia , Camundongos , Infiltração de Neutrófilos , Neutrófilos/imunologia , Neutrófilos/metabolismo , Neutrófilos/parasitologia , Peroxidase/metabolismo , Fatores de TempoRESUMO
OBJECTIVE: Ischemic stroke may result from transient or permanent reductions of regional cerebral blood flow. Polymorphonuclear neutrophils have been described as the earliest inflammatory cells to arrive in ischemic tissue. CXCR1/2 receptors are involved in the recruitment of these cells. However, the contribution of these chemokine receptors during transient brain ischemia in mice remains poorly understood. In this work, we investigated the effects of reparixin, an allosteric antagonist of CXCR1/2 receptors, in a model of middle cerebral artery occlusion and reperfusion in mice. METHODS: C57BL/6J male mice treated with reparixin or vehicle were subjected to a middle cerebral artery occlusion procedure 1 h after the treatment. Ninety minutes after ischemia induction, the monofilament that prevented blood flow was removed. Twenty-four hours after the reperfusion procedure, behavioral changes, including motor signs, were analyzed with the SmithKline/Harwell/lmperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. The animals were sacrificed, and brain tissue was removed for histological and biochemical analyses. Histological sections were stained with hematoxylin and eosin, neutrophil infiltration was estimated by myeloperoxidase activity and the inflammatory cytokine IL-iß was measured by ELISA. RESULTS: Pre-treatment with reparixin reduced the motor deficits observed in this model of ischemia and reperfusion. Myeloperoxidase activity and IL-iß were reduced in the reparixin-treated group. Histological analysis revealed that ischemic injury was also attenuated by reparixin pre-treatment. CONCLUSIONS: Our results suggest that the blockade of the CXCR1/2 receptors by reparixin promotes neuroprotective effects by reducing the levels of polymorphonuclear infiltration in the brain and the tissue damage associated with middle cerebral artery occlusion and reperfusion.
Assuntos
Lesões Encefálicas/prevenção & controle , Isquemia Encefálica/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Receptores de Interleucina-8A/antagonistas & inibidores , Receptores de Interleucina-8B/antagonistas & inibidores , Acidente Vascular Cerebral/tratamento farmacológico , Sulfonamidas/uso terapêutico , Animais , Lesões Encefálicas/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Peroxidase/metabolismo , Reprodutibilidade dos Testes , Sulfonamidas/farmacologia , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: Studies have shown that shrimps reduced the tensile strength of scars in rat skin. The aim of the present study was to assess the cytokine profile of rats fed shrimp. METHODS: Group 1 (control) received a regular diet and Group 2 (experimental) received a diet containing 33% shrimp for nine days. The two diets contained the same amounts of proteins, fats and carbohydrates. Serum cytokine levels were determined by ELISA and a segment of the jejunum was taken to investigate its histological morphology and eosinophil infiltrate. RESULTS: The experimental group had lower serum levels of interleukin-4 (IL-4) (14.4±1.9 versus 18.11±2.6pg/mL; p<0.05) and IL-10 (5.0±0.98 versus 7.5±1.2pg/mL; p<0.05) and higher levels of IL-6 (17.8±2.3 versus 3.2±0.4pg/mL, p<0.001) than controls. Morphologically, the shrimp-based diet caused an architectural disorganization of the intestinal mucosa and a greater amount of eosinophils in the jejunal villus. CONCLUSION: Our data suggests that shrimp consumption leads to a significant increase in the cytokine IL-6, a decrease in the immunomodulatory cytokine IL-10 in the serum of rats, and high eosinophil infiltration in the jejunum. The cytokine profile typical of inflammation and the histological aspect of the jejunum are compatible with food allergy.
OBJETIVO: Estudos mostraram que a dieta suplementada com camarão reduziu a resistência cicatricial na pele de ratos. Nesse contexto, o objetivo do presente estudo foi avaliar o perfil das citocinas de ratos que receberam dieta adicionada com camarão. MÉTODOS: Foram comparados um grupo controle e um grupo experimental, que receberam uma dieta enriquecida com camarão (33%) durante nove dias. As duas dietas continham quantidades semelhantes de proteínas, lipídeos, e carboidratos. Os níveis séricos de citocinas foram avaliados por ELISA, assim como um segmento de jejuno foi obtido para exame histológico da morfologia e infiltrado de eosinófilos. RESULTADOS: A dieta adicionada com camarão diminuiu os níveis séricos de IL-4 (14,4±1,9 versus 18,11±2,6pg/mL, p<0,05) e IL-10 (5,0±0,98 versus 7,5±1,2pg/mL, p<0,05 e aumentou os níveis séricos de IL-6 (3,2±0,4 versus 17,8±2,3pg/mL, p<0,001) quando comparada com os animais controle. Morfologicamente, a dieta adicionada com camarão causou uma desorganização da arquitetura da mucosa intestinal, juntamente com uma abundância de eosinófilos nas vilosidades jejunais. CONCLUSÃO: Os dados sugerem que a ingestão de dieta adicionada com camarão leva a um aumento significativo da citocina IL-6, juntamente com uma diminuição da citocina imunomoduladora IL-10 no soro de ratos e um infiltrado de eosinófilos no jejuno. O padrão inflamatório das citocinas e o aspecto histológico do jejuno são compatíveis com alergia alimentar.
Assuntos
Animais , Ratos , Citocinas , Dieta , Eosinófilos , Interleucinas , Ratos WistarRESUMO
OBJECTIVE: Ischemic stroke may result from transient or permanent reductions of regional cerebral blood flow. Polymorphonuclear neutrophils have been described as the earliest inflammatory cells to arrive in ischemic tissue. CXCR1/2 receptors are involved in the recruitment of these cells. However, the contribution of these chemokine receptors during transient brain ischemia in mice remains poorly understood. In this work, we investigated the effects of reparixin, an allosteric antagonist of CXCR1/2 receptors, in a model of middle cerebral artery occlusion and reperfusion in mice. METHODS: C57BL/6J male mice treated with reparixin or vehicle were subjected to a middle cerebral artery occlusion procedure 1 h after the treatment. Ninety minutes after ischemia induction, the monofilament that prevented blood flow was removed. Twenty-four hours after the reperfusion procedure, behavioral changes, including motor signs, were analyzed with the SmithKline/Harwell/lmperial College/Royal Hospital/Phenotype Assessment (SHIRPA) battery. The animals were sacrificed, and brain tissue was removed for histological and biochemical analyses. Histological sections were stained with hematoxylin and eosin, neutrophil infiltration was estimated by myeloperoxidase activity and the inflammatory cytokine IL-iβ was measured by ELISA. RESULTS: Pre-treatment with reparixin reduced the motor deficits observed in this model of ischemia and reperfusion. Myeloperoxidase activity and IL-iβ were reduced in the reparixin-treated group. Histological analysis revealed that ischemic injury was also attenuated by reparixin pre-treatment. CONCLUSIONS: Our results suggest that the blockade of the CXCR1/2 receptors by reparixin promotes neuroprotective effects by reducing the levels of polymorphonuclear infiltration in the brain and the tissue damage associated with middle cerebral artery occlusion and reperfusion.
Assuntos
Animais , Masculino , Camundongos , Lesões Encefálicas/prevenção & controle , Isquemia Encefálica/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , /antagonistas & inibidores , /antagonistas & inibidores , Acidente Vascular Cerebral/tratamento farmacológico , Sulfonamidas/uso terapêutico , Lesões Encefálicas/tratamento farmacológico , Ensaio de Imunoadsorção Enzimática , Fármacos Neuroprotetores/farmacologia , Peroxidase/metabolismo , Reprodutibilidade dos Testes , Sulfonamidas/farmacologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Phosphatidylinositol-3-kinase gamma (PI3Kgamma) plays an important role in the motility of leukocytes in several models of inflammation. In this work, the role of PI3Kgamma in experimental autoimmune encephalomyelitis (EAE) was investigated. EAE was induced in wild-type and PI3Kgamma deficient mice (PI3Kgamma(-)(/)(-)). WT animals had a peak of clinical symptoms around day 14 post-induction (p.i.). PI3Kgamma(-)(/)(-) animals developed milder EAE signs and peak of disease was noticed only on day 21 p.i. Better clinical outcome correlated with the absence of perivascular cuffs on day 14 p.i. and with decreased levels of CCL2 and CCL5 in brain of PI3Kgamma(-)(/)(-) mice. There was increased leukocyte rolling and adhesion in pial vessels, as assessed by intravital microscopy, at day 14 after EAE induction in WT mice. The latter parameters were unaltered in PI3Kgamma(-)(/)(-) mice subjected to EAE. Moreover, the PI3Kgamma inhibitor AS-605240 given just before the intravital microscopy failed to affect leukocyte rolling or adhesion. Finally, there was a significant increase in the number of apoptotic cells in the CNS of EAE-induced PI3Kgamma(-/-) mice. Our results suggest that PI3Kgamma is involved in EAE and plays a more important role in mediating leukocyte survival than leukocyte adhesion in this experimental model of multiple sclerosis.
Assuntos
Apoptose/imunologia , Autoimunidade/fisiologia , Encefalomielite Autoimune Experimental/enzimologia , Encefalomielite Autoimune Experimental/imunologia , Leucócitos/imunologia , Fosfatidilinositol 3-Quinases/metabolismo , Animais , Animais Recém-Nascidos , Apoptose/genética , Encéfalo/imunologia , Encéfalo/metabolismo , Encéfalo/patologia , Adesão Celular/genética , Adesão Celular/imunologia , Sobrevivência Celular/genética , Sobrevivência Celular/imunologia , Quimiocinas/metabolismo , Quimiotaxia de Leucócito/genética , Quimiotaxia de Leucócito/imunologia , Classe Ib de Fosfatidilinositol 3-Quinase , Modelos Animais de Doenças , Regulação para Baixo/genética , Regulação para Baixo/imunologia , Encefalomielite Autoimune Experimental/genética , Inibidores Enzimáticos/farmacologia , Tolerância Imunológica/genética , Tolerância Imunológica/imunologia , Isoenzimas/genética , Isoenzimas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Esclerose Múltipla/enzimologia , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Fosfatidilinositol 3-Quinases/genéticaRESUMO
Glycosylphosphatidylinositol-anchored mucin-like glycoproteins (tGPI-mucin) present on the surface of the cellular membrane of Trypanosoma cruzi forms activate toll-like receptors 2 (TLR2) on the surface of immune cells and induce the release of several mediators of inflammation which may be relevant in the context of Chagas disease. Here, we evaluated the ability of tGPI-mucins to activate murine peritoneal macrophages to induce nitric oxide (NO) and monocyte chemoattractant protein-1 (MCP-1/CCL2). We also investigated the ability of compounds which increase or mimic cyclic adenosine monophosphate (AMP) to modulate the production of NO and CCL2. Our data show that elevation of intracellular levels of cyclic AMP prevents the release of NO and CCL2 induced by tGPI-mucins in macrophages. Overall, the release of CCL2 was decreased to a greater extent and at lower concentrations of cyclic AMP-modifying agents than the production of NO. It is suggested that the elevation of cyclic AMP during T. cruzi infection may modify the release of pro-inflammatory mediators and alter significantly the course of T. cruzi infection.