TY - JOUR
T1 - Maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury
AU - Lei, Jun
AU - Rosenzweig, Jason M.
AU - Mishra, Manoj K.
AU - Alshehri, Wael
AU - Brancusi, Flavia
AU - McLane, Mike
AU - Almalki, Ahmad
AU - Bahabry, Rudhab
AU - Arif, Hattan
AU - Rozzah, Rayyan
AU - Alyousif, Ghada
AU - Shabi, Yahya
AU - Alhehaily, Nader
AU - Zhong, Wenyu
AU - Facciabene, Andrea
AU - Kannan, Sujatha
AU - Kannan, Rangaramanujam M.
AU - Burd, Irina
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-017-06113-2
DO - 10.1038/s41598-017-06113-2
M3 - Article
C2 - 28733619
AN - SCOPUS:85025446022
SN - 2045-2322
VL - 7
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 6106
ER -