ABSTRACT
No abstract available.
Subject(s)
Humans , Animals , Central Nervous System/virology , Central Nervous System/pathology , Central Nervous System/immunology , Cytokines/metabolism , Cytokines/immunology , Demyelinating Diseases/virology , Demyelinating Diseases/immunology , Disease Models, Animal , Inflammation/virology , Multiple Sclerosis/virology , Multiple Sclerosis/immunology , T-Lymphocytes/immunology , Theilovirus/pathogenicity , Theilovirus/immunologyABSTRACT
Multiple episodes of blood-brain barrier disruption were induced by sequential intraspinal injections of ethidium bromide. In addition to the barrier disruption, there was toxic demyelination and exposure of myelin components to the immune system. Twenty-seven 3-month-old Wistar rats received 2, 3 or 4 injections of 1 mul of either 0.1 percent ethidium bromide in normal saline (19 rats) or 0.9 percent saline (8 rats) at different levels of the spinal cord. The time intervals between the injections ranged from 28 to 42 days. Ten days after the last injection, all rats were perfused with 2.5 percent glutaraldehyde. The spinal sections were evaluated macroscopically and by light and transmission electron microscopy. All the lesions demonstrated a mononuclear phagocytic infiltrate apparently removing myelin. Lymphocytes were not conspicuos and were found in only 34 percent of the lesions. No perivascular cuffings were detected. In older lesions (38 days and older) they were found only within Virchow-Robin spaces. This result suggests that multiple blood-brain barrier disruptions with demyelination and exposure of myelin components to the immune system were not sufficient to induce an immune-mediated reaction in the central nervous system.
Subject(s)
Animals , Rats , Female , Blood-Brain Barrier/immunology , Demyelinating Diseases/chemically induced , Demyelinating Diseases/immunology , Ethidium/toxicity , Multiple Sclerosis/immunology , Nicotinic Antagonists/toxicity , Spinal Cord/immunology , Central Nervous System/immunology , Central Nervous System/pathology , Demyelinating Diseases/pathology , Ethidium/metabolism , Injections, Spinal , Lymphocytes/ultrastructure , Microscopy, Electron , Multiple Sclerosis/pathology , Myelin Basic Protein , Nicotinic Antagonists/metabolism , Rats, WistarABSTRACT
O sistema nervoso central é considerado um alvo precoce na infecção pelo vírus da imunodeficiência adquirida humana (HIV-1). Este trabalho teve por objetivo determinar por enzima imunoensaio (ELISA) a presença de reatividade imunológica para proteína básica da mielina (MBP) e para a seqüência de aminoácidos 68-84 da MBP exposta somente após degradação parcial ou total da MBP. Foram analisados soro e líquido cefalorraquiano (CSF) de 20 indivíduos HIV positivos, sendo 14 pacientes com o complexo demencial da AIDS (CDC estágio IV) e 6 indivíduos asintomáticos (CDC estágio II). Os grupos controle incluíram pacientes HIV negativos com várias doenças neurológicas como: demência multi-infarto, esclerose múltipla e indivíduos sem qualquer alteração neurológica ou cognitiva. A eletroforese em SDS-PAGE mostrou acentuada produção oligoclonal de imunoglobulinas no CSF dos pacientes com esclerose múltipla e dos indivíduos infectados pelo HIV. Intensa produção intratecal de IgG para o fragmento 68-84 da MBP foi observada de forma consistente, principalmente nos pacientes com ADC e HIV+ assintomáticos. Observou-se um paralelismo entre o grau de comprometimento clínico-neurológico/cognitivo, inclusive o aparecimento de placas de desmielinização com a intensidade da reação imunológica intratecal para os componentes do sistema nervoso central. Evidência de reatividade imunológica intratecal para o epítopo imunodominante 68-84 da mielina durante os estágios iniciais da infecção pelo vírus HIV-1, indica um comprometimento precoce do SNC associado a processo de desmielinização ativa silenciosa.