Demyelination in experimental intraventricular neurocysticercosis.

Neurocysticercosis (NCC) is classified as a neglected tropical disease, which affects mainly Latin America and Africa in spite of some reports in North America and Europe. NCC represents the cause of up to 30% of the reported cases of epilepsy in endemic countries. The NCC injuries present direct relation to the development stage, location, and number of parasites as well as to the host immune response. This study aimed the characterization of the inflammatory response and tissue injuries by means of the analyses of the periventricular and parenchymatous demyelination through the experimental intraventricular NCC infection. Therefore, BALB/c mice were submitted to experimental NCC inoculation with Taenia crassiceps cysticerci. Their brains were removed at 7, 30, 60, and 90 days after the inoculation (DAI), and analyzed after staining with hematoxylin and eosin (HE), Luxol Fast Blue, and Nissl. It was possible to observe ventriculomegaly, inflammatory infiltration composed by polymorphonuclear and mononuclear cells, and foamy macrophages. The presence of inflammatory cells was associated with neurodegeneration detected by the areas with demyelination observed initially in the periventricular area and lately in the parenchyma. In conclusion, the presence of cysticerci and the consequent inflammation were able to promote initial periventricular demyelination followed by parenchymatous demyelination as the infection progressed.

Demyelination in experimental intraventricular neurocysticercosis / Desmielinização na neurocisticercose intraventricular experimental

Abstract Neurocysticercosis (NCC) is classified as a neglected tropical disease, which affects mainly Latin America and Africa in spite of some reports in North America and Europe. NCC represents the cause of up to 30% of the reported cases of epilepsy in endemic countries. The NCC injuries present direct relation to the development stage, location, and number of parasites as well as to the host immune response. This study aimed the characterization of the inflammatory response and tissue injuries by means of the analyses of the periventricular and parenchymatous demyelination through the experimental intraventricular NCC infection. Therefore, BALB/c mice were submitted to experimental NCC inoculation with Taenia crassiceps cysticerci. Their brains were removed at 7, 30, 60, and 90 days after the inoculation (DAI), and analyzed after staining with hematoxylin and eosin (HE), Luxol Fast Blue, and Nissl. It was possible to observe ventriculomegaly, inflammatory infiltration composed by polymorphonuclear and mononuclear cells, and foamy macrophages. The presence of inflammatory cells was associated with neurodegeneration detected by the areas with demyelination observed initially in the periventricular area and lately in the parenchyma. In conclusion, the presence of cysticerci and the consequent inflammation were able to promote initial periventricular demyelination followed by parenchymatous demyelination as the infection progressed.

Resumo A neurocisticercose (NCC) é classificada como uma doença tropical negligenciada que afeta principalmente a América Latina e a África, apesar de alguns relatos na América do Norte e na Europa. A NCC é responsável por cerca de 30% dos casos de epilepsia em países endêmicos. Estas lesões parecem ter estreita relação com o estádio de desenvolvimento, com a localização e o número de parasitas, bem como a resposta imune do hospedeiro. O presente estudo objetivou caracterizar a resposta de células inflamatórias e as lesões teciduais pela análise da desmielinização periventricular e parenquimatosa ao longo da infecção experimental de NCC intraventricular. Para tanto, camundongos BALB/c foram submetidos a NCC experimental através da inoculação de cisticercos de Taenia crassiceps. O encéfalo foi retirado aos 7, 30, 60 e 90 dias após inoculação (DAI) e analisado após coloração por Hematoxilina e Eosina (HE), Luxol Fast Blue e Nissl. Observou-se ventriculomegalia, processo de infiltração inflamatório composto por células polimorfonucleares, mononucleares e macrófagos espumosos. A presença de células inflamatórias foi associada com neurodegeneração, observada pelas áreas de desmielinização que foram inicialmente periventricular e mais tardiamente no parênquima. Em conclusão, observa-se que a presença dos cisticercos e a inflamação foram capazes de promover desmielinização periventricular inicial e parenquimatosa conforme houve progressão tardia da infecção.

Taenia crassiceps antigens induce a Th2 immune response and attenuate injuries experimentally induced by neurotoxoplasmosis in BALB/c mice.

Toxoplasma gondii is a pathogenic agent responsible for causing both systemic and local disease which elicits a typically pro-inflammatory, Th1 immune response. Taenia crassiceps antigen induces a Th2 immune response that immunomodulates Th1 based infections. Therefore the aim of this study was to evaluate whether T. crassiceps cysticerci antigens are able to modulate the inflammatory response triggered in experimental neurotoxoplasmosis (NT). BALB/c mice were inoculated with T. gondii cysts and/or cysticerci antigens and euthanized at 60 and 90days after inoculation (DAI). The histopathology of the brains and cytokines produced by spleen cells culture were performed. The animals from the NT group, 90DAI (NT90), presented greater intensity of lesions such as vasculitis, meningitis and microgliosis and cytokines from Th1 profile characterized by high levels of IFN-gamma. While in the T. crassiceps antigens group, 60DAI, there were more discrete lesions and high levels of IL-4, a Th2 cytokine. In the NT co-inoculated with cysticerci antigens group the parenchyma lesions were more discrete with lower levels of IFN-gamma and higher levels of IL-4 when compared to NT90. Therefore the inoculation of T. crassiceps antigens attenuated the brain lesions caused by T. gondii inducing a Th2 immune response.

Cellular immune response in intraventricular experimental neurocysticercosis.

Neurocysticercosis (NCC) is considered a neglected parasitic infection of the human central nervous system. Its pathogenesis is due to the host immune response, stage of evolution and location of the parasite. The aim of this study was to evaluate the in situ and systemic immune response through cytokines dosage (IL-4, IL-10, IL-17 and IFN-γ) as well as the local inflammatory response of the experimental NCC with Taenia crassiceps. The in situ and systemic cellular and inflammatory immune response were evaluated through the cytokines quantification at 7, 30, 60 and 90 days after inoculation and histopathological analysis. All cysticerci were found within the cerebral ventricles. There was a discrete intensity of inflammatory cells of mixed immune profile, polymorphonuclear and mononuclear cells, at the beginning of the infection and predominance of mononuclear cells at the end. The systemic immune response showed a significant increase in all the analysed cytokines and predominance of the Th2 immune profile cytokines at the end of the infection. These results indicate that the location of the cysticerci may lead to ventriculomegaly. The acute phase of the infection showed a mixed Th1/Th17 profile accompanied by high levels of IL-10 while the late phase showed a Th2 immune profile.

Experimental encephalitis caused by Taenia crassiceps cysticerci in mice / Encefalite experimental causada por cisticercos de Taenia crassiceps em camundongos

OBJECTIVES: To present the experimental model of neurocysticercosis (NCC) caused by Taenia crassiceps cysticerci, to describe the inflammatory process, susceptibility, or resistance of BALB/c and C57BL/6 mice to this infection, and to describe the host-parasite relationship. METHODS: The animals were intracranially inoculated with initial stage T. crassiceps cysticerci. They were euthanized at 7, 30, 60, and 90 days after the inoculation. Their encephala were removed for the histopathologic analysis, classification of the parasites, and inflammatory lesions. RESULTS: Experimental NCC was observed on both mice lineages. BALB/c mice presented inflammatory lesions with greater intensity, inducing necrosis on late stage parasites, and with an acute inflammation pattern, while C57BL/6 mice showed greater capability on provoking early necrosis in the cysticerci, which showed a chronic inflammation pattern. CONCLUSIONS: This experimental model induced NCC on mice with characteristic inflammation and lesions. C57BL/6 mice were able to induce precocious necrosis of the parasites presenting inflammatory lesions with lower intensity.

OBJETIVOS: Apresentar o modelo experimental de neurocisticercose (NCC) com cisticercos de Taenia crassiceps, descrever a inflamação, suscetibilidade e resistência em camundongos BALB/c e C57BL/6, caracterizando melhor a relação parasito-hospedeiro. MÉTODOS: Os animais foram inoculados intracranialmente com cisticercos de T. crassiceps em estádio inicial e eutanasiados aos 7, 30, 60 e 90 dias após a infecção. Retiraram-se os encéfalos para análise histopatológica, classificação dos parasitos e lesões inflamatórias. RESULTADOS: Foi possível induzir NCC nas duas linhagens de camundongos utilizados como modelo experimental. Os animais BALB/c apresentaram lesões inflamatórias mais intensas do que os camundongos C57BL/6 e induziram nos parasitos necrose na fase tardia com padrão inflamatório agudo. Os C57BL/6 mostraram-se mais hábeis em provocar necrose precocemente nos cisticercos, mas com padrão inflamatório crônico. CONCLUSÕES: Este modelo experimental induziu NCC nos animais com inflamações e lesões. Os camundongos C57BL/6 foram hábeis em induzir precocemente necrose nos parasitos, apresentando lesões inflamatórias com menor intensidade.

Experimental encephalitis caused by Taenia crassiceps cysticerci in mice.

OBJECTIVES: To present the experimental model of neurocysticercosis (NCC) caused by Taenia crassiceps cysticerci, to describe the inflammatory process, susceptibility, or resistance of BALB/c and C57BL/6 mice to this infection, and to describe the host-parasite relationship. METHODS: The animals were intracranially inoculated with initial stage T. crassiceps cysticerci. They were euthanized at 7, 30, 60, and 90 days after the inoculation. Their encephala were removed for the histopathologic analysis, classification of the parasites, and inflammatory lesions. RESULTS: Experimental NCC was observed on both mice lineages. BALB/c mice presented inflammatory lesions with greater intensity, inducing necrosis on late stage parasites, and with an acute inflammation pattern, while C57BL/6 mice showed greater capability on provoking early necrosis in the cysticerci, which showed a chronic inflammation pattern. CONCLUSIONS: This experimental model induced NCC on mice with characteristic inflammation and lesions. C57BL/6 mice were able to induce precocious necrosis of the parasites presenting inflammatory lesions with lower intensity.