RESUMO
Naegleria fowleri causes a fatal disease known as primary amoebic meningoencephalitis. This condition is characterized by an acute inflammation that originates from the free passage of peripheral blood cells to the central nervous system through the alteration of the blood-brain barrier. In this work, we established models of the infection in rats and in a primary culture of endothelial cells from rat brains with the aim of evaluating the activation and the alterations of these cells by N. fowleri. We proved that the rat develops the infection similar to the mouse model. We also found that amoebic cysteine proteases produced by the trophozoites and the conditioned medium induced cytopathic effect in the endothelial cells. In addition, N. fowleri can decrease the transendothelial electrical resistance by triggering the destabilization of the tight junction proteins claudin-5, occludin, and ZO-1 in a time-dependent manner. Furthermore, N. fowleri induced the expression of VCAM-1 and ICAM-1 and the production of IL-8, IL-1ß, TNF-α, and IL-6 as well as nitric oxide. We conclude that N. fowleri damaged the blood-brain barrier model by disrupting the intercellular junctions and induced the presence of inflammatory mediators by allowing the access of inflammatory cells to the olfactory bulbs.
Assuntos
Barreira Hematoencefálica/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/metabolismo , Células Endoteliais/metabolismo , Naegleria fowleri/metabolismo , Naegleria fowleri/patogenicidade , Proteínas de Junções Íntimas/metabolismo , Animais , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/patologia , Claudina-5/metabolismo , Cisteína Proteases/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Inflamação , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , Masculino , Meningoencefalite/parasitologia , Meningoencefalite/patologia , Camundongos , Mucosa/parasitologia , Mucosa/patologia , Ocludina/metabolismo , Ratos , Ratos Wistar , Trofozoítos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Conchas Nasais/patologia , Molécula 1 de Adesão de Célula Vascular/metabolismo , Proteína da Zônula de Oclusão-1/metabolismoRESUMO
Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and causes severe cardiac and brain damage, leading to behavioral alterations in humans and animals. However, the mechanisms involved in memory impairment during T. cruzi infection remain unknown. It has long been recognized that the enzymatic activities of acetylcholinesterase (AChE) and Na+, K+-ATPase are linked with memory dysfunction during other trypanosomiasis. Thus, the aim of this study was to evaluate the involvement of cerebral AChE and Na+, K+-ATPase activities in the memory impairment during T. cruzi (Colombian strain) infection. A significant decrease on latency time during the inhibitory avoidance task was observed in animals infected by T. cruzi compared to uninfected animals, findings compatible to memory dysfunction. Moreover, the cerebral AChE activity increased, while the Na+, K+-ATPase decreased in T. cruzi infected compared to uninfected animals. Histopathology revealed mild to moderate multifocal gliosis in the cerebral cortex and light focal meningeal lymphoplasmacytic infiltrate, which may have contributed to memory loss. Based on these evidences, we can conclude that T. cruzi (Colombian strain) causes memory impairment in mice experimentally infected. Moreover, the changes in AChE and Na+, K+-ATPase activities may be considered a mechanism involved in disease pathogenesis.
Assuntos
Acetilcolinesterase/metabolismo , Infecções Protozoárias do Sistema Nervoso Central/enzimologia , Córtex Cerebral/enzimologia , Transtornos da Memória/enzimologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Trypanosoma cruzi/patogenicidade , Animais , Comportamento Animal , Encéfalo/enzimologia , Encéfalo/parasitologia , Encéfalo/patologia , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/patologia , Infecções Protozoárias do Sistema Nervoso Central/psicologia , Córtex Cerebral/parasitologia , Córtex Cerebral/patologia , Doença de Chagas , Modelos Animais de Doenças , Feminino , Gliose/enzimologia , Gliose/parasitologia , Gliose/patologia , Coração , Humanos , Transtornos da Memória/parasitologia , Transtornos da Memória/patologia , Transtornos da Memória/psicologia , Camundongos , Tripanossomíase/parasitologia , Tripanossomíase/psicologiaRESUMO
Naegleria fowleri causes acute and fulminant primary amoebic meningoencephalitis. This microorganism invades its host by penetrating the olfactory mucosa and then traveling up the mesaxonal spaces and crossing the cribriform plate; finally, the trophozoites invade the olfactory bulbs. During its invasion, the protozoan obtains nutrients such as proteins, lipids, carbohydrates, and cationic ions (e.g., iron, calcium, and sodium) from the host. However, the mechanism by which these ions are obtained, particularly iron, is poorly understood. In the present study, we evaluated the ability of N. fowleri to degrade iron-binding proteins, including hololactoferrin, transferrin, ferritin, and hemoglobin. Zymography assays were performed for each substrate under physiological conditions (pH 7 at 37°C) employing conditioned medium (CM) and total crude extracts (TCEs) of N. fowleri. Different degradation patterns with CM were observed for hololactoferrin, transferrin, and hemoglobin; however, CM did not cause ferritin degradation. In contrast, the TCEs degraded only hololactoferrin and transferrin. Inhibition assays revealed that cysteine proteases were involved in this process. Based on these results, we suggest that CM and TCEs of N. fowleri degrade iron-binding proteins by employing cysteine proteases, which enables the parasite to obtain iron to survive while invading the central nervous system.
Assuntos
Infecções Protozoárias do Sistema Nervoso Central/metabolismo , Cisteína Proteases/metabolismo , Interações Hospedeiro-Patógeno , Ferro/metabolismo , Proteólise , Animais , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/patologia , Proteínas de Ligação ao Ferro/metabolismo , Lactoferrina/metabolismo , Naegleria fowleri/enzimologia , Naegleria fowleri/patogenicidade , Bulbo Olfatório/metabolismo , Bulbo Olfatório/patologia , Transferrina/metabolismo , Trofozoítos/metabolismoRESUMO
This study aimed to characterize astrocytic and microglial response in the central nervous system (CNS) of equines experimentally infected with T. evansi. The experimental group comprised males and females with various degrees of crossbreeding, ages between four and seven years. The animals were inoculated intravenously with 10(6) trypomastigotes of T. evansi originally isolated from a naturally infected dog. All equines inoculated with T. evansi were observed until they presented symptoms of CNS disturbance, characterized by motor incoordination of the pelvic limbs, which occurred 67 days after inoculation (DAI) and 124 DAI. The animals in the control group did not present any clinical symptom and were observed up to the 125th DAI. For this purpose the HE histochemical stain and the avidin biotin peroxidase method was used. Lesions in the CNS of experimentally infected horses were those of a wide spread non suppurative meningoencephalomyelitis.The severity of lesions varied in different parts of the nervous system, reflecting an irregular distribution of inflammatory vascular changes. The infiltration of mononuclear cells was associated with anisomorphic gliosis and reactive microglia was identified. The intensity of the astrocytic response in the CNS of the equines infected by T. evansi characterizes the importance of the performance of these cells in this trypanosomiasis. The characteristic gliosis observed in the animals in this experiment suggests the ability of these cells as mediators of immune response. The parasite, T. evansi, was not identified in the nervous tissues.
Assuntos
Astrócitos/patologia , Encéfalo/patologia , Infecções Protozoárias do Sistema Nervoso Central/veterinária , Doença de Chagas/veterinária , Doenças dos Cavalos/patologia , Microglia/patologia , Trypanosoma/imunologia , Animais , Astrócitos/parasitologia , Encéfalo/imunologia , Infecções Protozoárias do Sistema Nervoso Central/imunologia , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/patologia , Doença de Chagas/imunologia , Doença de Chagas/parasitologia , Doença de Chagas/patologia , Doença Crônica , Encefalomielite/imunologia , Encefalomielite/parasitologia , Encefalomielite/patologia , Encefalomielite/veterinária , Feminino , Doenças dos Cavalos/imunologia , Doenças dos Cavalos/parasitologia , Cavalos , Masculino , Meningoencefalite/imunologia , Meningoencefalite/parasitologia , Meningoencefalite/patologia , Meningoencefalite/veterinária , Microglia/parasitologia , Índice de Gravidade de Doença , Trypanosoma/classificaçãoRESUMO
This study aimed to characterize astrocytic and microglial response in the central nervous system (CNS) of equines experimentally infected with T. evansi. The experimental group comprised males and females with various degrees of crossbreeding, ages between four and seven years. The animals were inoculated intravenously with 10(6) trypomastigotes of T. evansi originally isolated from a naturally infected dog. All equines inoculated with T. evansi were observed until they presented symptoms of CNS disturbance, characterized by motor incoordination of the pelvic limbs, which occurred 67 days after inoculation (DAI) and 124 DAI. The animals in the control group did not present any clinical symptom and were observed up to the 125th DAI. For this purpose the HE histochemical stain and the avidin biotin peroxidase method was used. Lesions in the CNS of experimentally infected horses were those of a wide spread non suppurative meningoencephalomyelitis.The severity of lesions varied in different parts of the nervous system, reflecting an irregular distribution of inflammatory vascular changes. The infiltration of mononuclear cells was associated with anisomorphic gliosis and reactive microglia was identified. The intensity of the astrocytic response in the CNS of the equines infected by T. evansi characterizes the importance of the performance of these cells in this trypanosomiasis. The characteristic gliosis observed in the animals in this experiment suggests the ability of these cells as mediators of immune response. The parasite, T. evansi, was not identified in the nervous tissues.
Este estudo objetivou caracterizar a participação astrocítica e microglial no sistema nervoso central (SNC) de eqüinos experimentalmente infectados com T. evansi. O grupo experimental foi formado por machos e fêmeas com vários graus de cruzamentos e idade variando entre quatro e sete anos. Os animais foram inoculados com 10(6) tripomastigotas de T. evansi, originalmente isolada de um cão infectado naturalmente. Todos os eqüinos inoculados foram observados até o aparecimento dos sintomas neurológicos, caracterizados por incoordenação motora dos membros pélvicos, o qual ocorreu entre 67 e 124 dias após a inoculação (DPI). Os animais do grupo controle não apresentaram sinais clínicos e foram observados até o 125º DPI. Para este propósito, foram utilizados os métodos histoquímicos (HE) e imunoistoquímicos do complexo avidina-biotina peroxidase (ABC). A lesão no sistema nervoso central (SNC) dos eqüinos infectados com T. evansi foi caracterizada como meningoencefalomielite não supurativa. A gravidade das lesões variou em diferentes segmentos do SNC, refletindo distribuição irregular das alterações vasculares. Infiltrado perivascular e meníngeo foi associado a gliose anisomórfica e microgliose reativa. A intensidade da resposta astrocítica no SNC dos equinos infectados com T. evansi caracteriza a importância da performance destas células nas tripanossomíases. A gliose observada nos animais deste experimento sugerem a habilidade destas células como mediadoras da resposta imune. T. evansi não foi identificado no parênquima do SNC.
Assuntos
Animais , Feminino , Masculino , Astrócitos/patologia , Encéfalo/patologia , Infecções Protozoárias do Sistema Nervoso Central/veterinária , Doença de Chagas/veterinária , Doenças dos Cavalos/patologia , Microglia/patologia , Trypanosoma/imunologia , Astrócitos/parasitologia , Encéfalo/imunologia , Doença Crônica , Infecções Protozoárias do Sistema Nervoso Central/imunologia , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/patologia , Doença de Chagas/imunologia , Doença de Chagas/parasitologia , Doença de Chagas/patologia , Encefalomielite/imunologia , Encefalomielite/parasitologia , Encefalomielite/patologia , Encefalomielite/veterinária , Cavalos , Doenças dos Cavalos/imunologia , Doenças dos Cavalos/parasitologia , Meningoencefalite/imunologia , Meningoencefalite/parasitologia , Meningoencefalite/patologia , Meningoencefalite/veterinária , Microglia/parasitologia , Índice de Gravidade de Doença , Trypanosoma/classificaçãoRESUMO
Toxoplasmosis is one of the most important diseases of the nervous central system, leading to severe symptoms and, many times, irreversible sequelae. This work demonstrated the main anatomopathological lesions caused by Toxoplasma gondii in brains from experimentally infected BALB/c mice. We analyzed 51 cases of mice that developed toxoplasmosis after experimental infection by intraperitoneal inoculation of blood, amniotic liquid and cerebrospinal fluid from fetuses, newly born children and pregnant women with clinical and laboratory signals of toxoplasmosis. In all experiments where we detected the parasite in mice we also detected pathological lesions in the animal brains with great polymorphism between experiments. Edema was the most found lesion in all cases. Besides, it was possible to demonstrate the inflammatory process in 82.4% of cases and necrosis in 64.7% of cases, in agreement with the literature that describes severe neurological damage in its hosts.
Assuntos
Encéfalo/patologia , Infecções Protozoárias do Sistema Nervoso Central/patologia , Toxoplasmose Animal/patologia , Animais , Encéfalo/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Feminino , Humanos , Recém-Nascido , Camundongos , Camundongos Endogâmicos BALB C , GravidezRESUMO
OBJECTIVES: The objective of this study was to evaluate clinical and microbiological characteristics of Chagas disease (ChD) with central nervous system (CNS) involvement in AIDS patients. METHODS: This was a retrospective study of clinical and laboratory findings of HIV-infected patients with a confirmed diagnosis of ChD involving the CNS during the period 1992-2007 at the "Francisco J. Muñiz" Infectious Diseases Hospital, Buenos Aires, Argentina. RESULTS: Of a total of 15 patients, 14 were male and the median age was 33 years (range 25-54 years). Seven out of nine had lived in a Chagas endemic area and 7/10 were intravenous drug users (IDUs). The disease was reactivated during corticosteroid therapy in three patients. Clinical manifestations were: headache (11/15), focal neurological deficits (9/15), fever (9/15), meningismus (7/15), seizures (7/15), altered mental status (5/15), and cardiac involvement (3/10). The median CD4 T-cell count at the time of reactivation was 64cells/microl (range 1-240). Twelve of 14 had positive serology for Trypanosoma cruzi; the two negative were IDUs. Cerebrospinal fluid (CSF) findings (median (range)): cell count 5/mm(3) (2-90), protein level 0.68g/l (0.1-1.84), and glucose level 0.45g/l (0.13-0.73). CSF direct examination for T. cruzi was positive in 11/13. Neuroimaging findings showed a single hypodense lesion in 7/14 and normal images in 2/14. Twelve patients were treated with benznidazole. The global mortality was 79% (11/14). CONCLUSIONS: ChD reactivation should be considered as a differential diagnosis of meningoencephalitis in HIV patients with low CD4 T-cell counts, previous residency in an endemic area, and/or IDUs. Whenever possible, lumbar puncture should be performed because of the high accuracy for early diagnosis.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS , Doença de Chagas/patologia , Infecções por HIV/complicações , Trypanosoma cruzi/patogenicidade , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/parasitologia , Infecções Oportunistas Relacionadas com a AIDS/patologia , Adulto , Animais , Argentina/epidemiologia , Encéfalo/diagnóstico por imagem , Encéfalo/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/epidemiologia , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/patologia , Líquido Cefalorraquidiano/parasitologia , Doença de Chagas/parasitologia , Feminino , Humanos , Masculino , Meningoencefalite/epidemiologia , Meningoencefalite/parasitologia , Meningoencefalite/patologia , Pessoa de Meia-Idade , Radiografia , Trypanosoma cruzi/isolamento & purificaçãoRESUMO
Toxoplasmosis is one of the most important diseases of the nervous central system, leading to severe symptoms and, many times, irreversible sequelae. This work demonstrated the main anatomopathological lesions caused by Toxoplasma gondii in brains from experimentally infected BALB/c mice. We analyzed 51 cases of mice that developed toxoplasmosis after experimental infection by intraperitoneal inoculation of blood, amniotic liquid and cerebrospinal fluid from fetuses, newly born children and pregnant women with clinical and laboratory signals of toxoplasmosis. In all experiments where we detected the parasite in mice we also detected pathological lesions in the animal brains with great polymorphism between experiments. Edema was the most found lesion in all cases. Besides, it was possible to demonstrate the inflammatory process in 82.4 percent of cases and necrosis in 64.7 percent of cases, in agreement with the literature that describes severe neurological damage in its hosts.
Assuntos
Animais , Feminino , Humanos , Recém-Nascido , Camundongos , Gravidez , Encéfalo/patologia , Infecções Protozoárias do Sistema Nervoso Central/patologia , Toxoplasmose Animal/patologia , Encéfalo/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Camundongos Endogâmicos BALB CRESUMO
The case of a 7 month-old baby boy is presented, with a history of several weeks of evolution of personality changes, convulsions and fever. While he was hospitalized, the brain image study showed multifocal cavity lesions, which varied from millimeters to 4 cm of diameter, not producing mass effect. Their biopsy revealed necrotizing encephalitis. In spite of treatment, the lesions progressed and the boy died. The autopsy demonstrated an extensive necrotizing encephalitis with fibrinoid necrotic arteritis, signs of organization, and the presence of parasitic elements with characteristics of trophozoites and cysts of free-living amoebas belonging to the genus Acanthamoeba or Balamuthia. In addition, hypoplasia-dysplasia of the thymus and signs of shock were found. The morphologic elements correspond to the disease described as granulomatous amebic encephalitis and the agent found was identified as Balamuthia mandrillaris (Centers for Diseases Control and Prevention, Atlanta, USA ).
Assuntos
Amebíase/parasitologia , Amoeba/isolamento & purificação , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Encefalite/parasitologia , Granuloma/parasitologia , Amebíase/epidemiologia , Amebíase/patologia , Amoeba/classificação , Animais , Infecções Protozoárias do Sistema Nervoso Central/epidemiologia , Infecções Protozoárias do Sistema Nervoso Central/patologia , Chile , Encefalite/epidemiologia , Encefalite/patologia , Evolução Fatal , Granuloma/epidemiologia , Granuloma/patologia , Humanos , Lactente , MasculinoRESUMO
The free-living amebas Naegleria and Acanthamoeba are recognized as causal agents of central nervous system infections. Recently a third free-living ameba, Balamuthia mandrillaris, was identified as the causal agent of granulomatous encephalitis in humans. We report a case of Balamuthia encephalitis in an immunocompetent school-age girl who presented cutaneous lesions that compromised the central portion of the face. The skin biopsy revealed granulomatous lesion with positive PCR for non-tuberculous Mycobacterium. We started treatment for atypical extrapulmonary mycobacteriosis. Nevertheless, the child was readmitted six months later, with progressive neurological involvement, dying about one year after the onset of cutaneous symptoms. The brain necropsy showed the presence of B. mandrillaris cysts and trophozoites. Balamuthia mandrillaris infection should be considered in the differential diagnosis of a patient with chronic granulomatous disease with neurologic symptoms.
Assuntos
Amebíase/parasitologia , Amoeba/isolamento & purificação , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Granuloma/parasitologia , Meningoencefalite/parasitologia , Dermatopatias Parasitárias/parasitologia , Amebíase/patologia , Amoeba/classificação , Animais , Infecções Protozoárias do Sistema Nervoso Central/patologia , Pré-Escolar , Evolução Fatal , Feminino , Granuloma/patologia , Humanos , Hospedeiro Imunocomprometido , Meningoencefalite/patologia , Dermatopatias Parasitárias/patologiaRESUMO
Central nervous system (CNS) damage can occur during Trypanosoma cruzi infection, especially in immunosuppressed patients. The enhanced susceptibility of C3H/He mice to CD8-mediated acute meningoencephalitis is associated with higher up-regulation of vascular cell adhesion molecule-1 (VCAM-1) on CNS vascular endothelia than in the less susceptible C57BL/6. Further, in vitro adhesion of activated peripheral blood cells to CNS blood vessels was abrogated by anti-VLA-4 antibodies that also inhibited cell migration into the CNS of T. cruzi-infected mice. Lastly, the reactivation of meningoencephalitis in immunosuppressed chronically infected mice was associated with VCAM-1 up-regulation. Therefore, we hypothesize that VLA-4/VCAM-1 pathway plays a pivotal role in the establishment of T. cruzi-elicited encephalitis.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções Protozoárias do Sistema Nervoso Central/imunologia , Doença de Chagas/imunologia , Integrina alfa4beta1/fisiologia , Meningoencefalite/imunologia , Transdução de Sinais/imunologia , Trypanosoma cruzi/imunologia , Molécula 1 de Adesão de Célula Vascular/fisiologia , Animais , Antígenos de Protozoários/análise , Linfócitos T CD8-Positivos/parasitologia , Adesão Celular/imunologia , Movimento Celular/imunologia , Infecções Protozoárias do Sistema Nervoso Central/metabolismo , Infecções Protozoárias do Sistema Nervoso Central/parasitologia , Infecções Protozoárias do Sistema Nervoso Central/patologia , Doença de Chagas/metabolismo , Doença de Chagas/parasitologia , Doença de Chagas/patologia , Doença Crônica , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/imunologia , Endotélio Vascular/parasitologia , Endotélio Vascular/patologia , Feminino , Predisposição Genética para Doença , Imunofenotipagem , Imunossupressores/administração & dosagem , Integrina alfa4beta1/biossíntese , Molécula 1 de Adesão Intercelular/biossíntese , Leucócitos Mononucleares/química , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/parasitologia , Meningoencefalite/metabolismo , Meningoencefalite/parasitologia , Meningoencefalite/patologia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Recidiva , Molécula 1 de Adesão de Célula Vascular/biossínteseRESUMO
We describe the pathologic alterations of the central nervous system (CNS) observed in experimental tegumentary leishmaniasis in BALB/c and Swiss mice. The mice were subcutaneously infected with 10(4) amastigotes of Leishmania (Leishmania) amazonensis. Animals were killed and brains were removed for histologic and immunocytochemical studies. Histologic examination showed that 66.6% of infected mice had a discrete hyperemia and inflammatory infiltrate in the meninges, composed of mononuclear cells and neutrophils with no detectable parasites. However, parasitized macrophages were detected in the cerebral parenchyma, as well as mast cells, lymphocytes, and polymorphonuclear cells. Necrosis in the cerebral parenchyma was also observed. Confocal fluorescence microscopy showed that CD8+ T lymphocytes are the major component of the inflammatory infiltrate in the CNS. In addition to these cells, CD4+, CD11b, and dendritic cells are present, in small numbers, in the inflammatory processes of the CNS. Thus, L. amazonensis is able to cross the blood-brain barrier and cause significant pathologic changes in the CNS.