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

Jun Lei, Jason M. Rosenzweig, Manoj K. Mishra, Wael Alshehri, Flavia Brancusi, Mike McLane, Ahmad Almalki, Rudhab Bahabry, Hattan Arif, Rayyan Rozzah, Ghada Alyousif, Yahya Shabi, Nader Alhehaily, Wenyu Zhong, Andrea Facciabene, Sujatha Kannan, Rangaramanujam M. Kannan, Irina Burd

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number6106
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury'. Together they form a unique fingerprint.

Cite this