期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 10, 期 444, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aar2749
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资金
- Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
- Institutos Nacionais de Pesquisa-Instituto Nacional de Neurociencia Translacional
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico
- Institutos Nacionais de Pesquisa-Inovacao em Medicamentos e Identificacao de Novos Alvos Terapeuticos
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior
- Financiadora de Estudos e Projetos
Although congenital Zika virus (ZIKV) exposure has been associated with microcephaly and other neurodevelopmental disorders, long-term consequences of perinatal infection are largely unknown. We evaluated short-and long-term neuropathological and behavioral consequences of neonatal ZIKV infection in mice. ZIKV showed brain tropism, causing postnatal-onset microcephaly and several behavioral deficits in adulthood. During the acute phase of infection, mice developed frequent seizures, which were reduced by tumor necrosis factor-alpha (TNF-alpha) inhibition. During adulthood, ZIKV replication persisted in neonatally infected mice, and the animals showed increased susceptibility to chemically induced seizures, neurodegeneration, and brain calcifications. Altogether, the results show that neonatal ZIKV infection has long-term neuropathological and behavioral complications in mice and suggest that early inhibition of TNF-alpha-mediated neuroinflammation might be an effective therapeutic strategy to prevent the development of chronic neurological abnormalities.
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