Maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury
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 stud...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2017
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/94b92b65e3334f63862e3e681e4f3478 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:94b92b65e3334f63862e3e681e4f3478 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:94b92b65e3334f63862e3e681e4f34782021-12-02T11:40:32ZMaternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury10.1038/s41598-017-06113-22045-2322https://doaj.org/article/94b92b65e3334f63862e3e681e4f34782017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06113-2https://doaj.org/toc/2045-2322Abstract 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.Jun LeiJason M. RosenzweigManoj K. MishraWael AlshehriFlavia BrancusiMike McLaneAhmad AlmalkiRudhab BahabryHattan ArifRayyan RozzahGhada AlyousifYahya ShabiNader AlhehailyWenyu ZhongAndrea FacciabeneSujatha KannanRangaramanujam M. KannanIrina BurdNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q 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 Maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Jun Lei |
| title |
Maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury |
| title_short |
Maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury |
| title_full |
Maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury |
| title_fullStr |
Maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury |
| title_full_unstemmed |
Maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury |
| title_sort |
maternal dendrimer-based therapy for inflammation-induced preterm birth and perinatal brain injury |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/94b92b65e3334f63862e3e681e4f3478 |
| work_keys_str_mv |
AT junlei maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury AT jasonmrosenzweig maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury AT manojkmishra maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury AT waelalshehri maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury AT flaviabrancusi maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury AT mikemclane maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury AT ahmadalmalki maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury AT rudhabbahabry maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury AT hattanarif maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury AT rayyanrozzah maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury AT ghadaalyousif maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury AT yahyashabi maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury AT naderalhehaily maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury AT wenyuzhong maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury AT andreafacciabene maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury AT sujathakannan maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury AT rangaramanujammkannan maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury AT irinaburd maternaldendrimerbasedtherapyforinflammationinducedpretermbirthandperinatalbraininjury |
| _version_ |
1718395595549310976 |