Author(s):
Sousa, Jorge Rodrigues de ; Azevedo, Raimunda do Socorro da Silva ; Martins Filho, Arnaldo Jorge ; Ara?jo, Marialva Tereza Ferreira de ; Cruz, Ermelinda do Ros?rio Moutinho ; Vasconcelos, Barbara Cristina Baldez ; Cruz, Ana Cec?lia Ribeiro ; Oliveira, Consuelo Silva de ; Martins, Livia Car?cio ; Vasconcelos, Beatriz Helena Baldez ; Casseb, Livia Medeiros Neves ; Chiang, Jannifer Oliveira ; Quaresma, Juarez Antonio Sim?es ; Vasconcelos, Pedro Fernando da Costa
Date: 2018
Origin: Oasisbr
Subject(s): Zika virus / patogenicidade; Infec??o pelo Zika virus / patologia; Microcefalia / mortalidade; Infec??es por Flavivirus; Sistema Nervoso Central / anormalidades; Complexos Multiproteicos; Inflamassomos / gen?tica; Piroptose / gen?tica; Apoptose / gen?tica; C?rtex Cerebral / les?es
Description
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
State University of Par?. Center of Biological and Health Sciences. Bel?m, PA, Brazil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / State University of Par?. Center of Biological and Health Sciences. Bel?m, PA, Brazil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Federal University of Par?. Tropical Medicine Center. Bel?m, PA, Brazil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / State University of Par?. Center of Biological and Health Sciences. Bel?m, PA, Brazil / Federal University of Par?. Tropical Medicine Center. Bel?m, PA, Brazil.
Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / State University of Par?. Center of Biological and Health Sciences. Bel?m, PA, Brazil.
Zika virus (ZIKV) has caused substantial concern worldwide owing to its association with severe birth defects, such as microcephaly and other congenital malformations. Inflammasomes, i.e., multi-protein complexes that induce inflammation and pyroptosis, are predicted to contribute to the immune response to this flavivirus. Accordingly, in this study, the in situ inflammasome response was evaluated in fatal cases of ZIKV-linked microcephaly. Brain tissue samples were collected from eight babies, including four ZIKV-positive microcephalic neonates who died after birth and four flavivirus-negative neonatal controls who died of other causes and whose central nervous system (CNS) architecture was preserved. In the ZIKV-positive newborn/stillbirth babies, the major histopathological alterations included atrophy of the cortical layer, a predominance of mononuclear cell infiltration in the Virchow-Robin space, neuronal necrosis, vacuolization and neuronal degeneration, neuronophagy, and gliosis. An immunohistochemical analysis of tissues in the neural parenchyma showed significantly higher expression of the receptors NLRP1, NLRP3, and AIM2, cytokines IL-1?, IL-18, and IL-33, and enzymes caspase 1, iNOS, and arginase 1 in ZIKV-positive microcephaly cases than in flavivirus-negative controls. These results suggest that inflammasome activation can aggravate the neuroinflammatory response and consequently increase CNS damage in neonates with fetal neural ZIKV infection and microcephaly.
