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Sci Rep ; 7(1): 6106, 2017 07 21.
Article in English | MEDLINE | ID: mdl-28733619

ABSTRACT

Preterm birth is a major risk factor for adverse neurological outcomes in ex-preterm children, including motor, cognitive, and behavioral disabilities. N-acetyl-L-cysteine therapy has been used in clinical studies; however, it requires doses that cause significant side effects. In this study, we explore the effect of low dose N-acetyl-L-cysteine therapy, delivered using a targeted, systemic, maternal, dendrimer nanoparticle (DNAC), in a mouse model of intrauterine inflammation. Our results demonstrated that intraperitoneal maternal DNAC administration significantly reduced the preterm birth rate and altered placental immune profile with decreased CD8+ T-cell infiltration. Furthermore, we demonstrated that DNAC improved neurobehavioral outcomes and reduced fetal neuroinflammation and long-term microglial activation in offspring. Our study is the first to provide evidence for the role of CD8+ T-cell in the maternal-fetal interface during inflammation and further support the efficacy of DNAC in preventing preterm birth and prematurity-related outcomes.


Subject(s)
Brain Injuries/drug therapy , Brain Injuries/etiology , Dendrimers/therapeutic use , Inflammation/complications , Premature Birth/drug therapy , Premature Birth/etiology , Animals , Birth Rate , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Dendrimers/pharmacology , Disease Models, Animal , Female , Humans , Infant, Newborn , Lipopolysaccharides/immunology , Mice , Microglia/immunology , Microglia/metabolism , Nanoparticles , Placenta/immunology , Placenta/metabolism , Pregnancy , Yolk Sac/immunology , Yolk Sac/metabolism
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