Maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury

Sci Rep. 2017 Jul 21;7(1):6106. doi: 10.1038/s41598-017-06113-2.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Dendrimers
  • Lipopolysaccharides