Administration of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) is believed to be an effective method for treating neurodevelopmental disorders. In this study, we investigated the possibility of hUC-MSCs treatment of neonatal hypoxic/ischemic brain injury associated with maternal immune activation and the underlying mechanism. We established neonatal rat models of hypoxic/ischemic brain injury by exposing pregnant rats to lipopolysaccharide on day 16 or 17 of pregnancy. Rat offspring were intranasally administered hUC-MSCs on postnatal day 14. We found that polypyrimidine tract-binding protein-1 (PTBP-1) participated in the regulation of lipopolysaccharide-induced maternal immune activation, which led to neonatal hypoxic/ischemic brain injury. Intranasal delivery of hUC-MSCs inhibited PTBP-1 expression, alleviated neonatal brain injury-related inflammation, and regulated the number and function of glial fibrillary acidic protein-positive astrocytes, thereby promoting plastic regeneration of neurons and improving brain function. These findings suggest that hUC-MSCs can effectively promote the repair of neonatal hypoxic/ischemic brain injury related to maternal immune activation through inhibition of PTBP-1 expression and astrocyte activation.

Stem Cell Clinical Research Center,National Joint Engineering Laboratory,Regenerative Medicine Center,The First Affiliated Hospital of Dalian Medical University,Dalian,Liaoning Province,China;Dalian Innovation Institute of Stem Cells and Precision Medicine,Dalian,Liaoning Province,China;Department of Neurology,The First Affiliated Hospital of Dalian Medical University,Dalian,Liaoning Province,China;College of Life Science,Liaoning Normal University,Dalian,Liaoning Province,China

[1]Yang Jiao;Yue-Tong Sun;Nai-Fei Chen;Li-Na Zhou;Xin Guan;Jia-Yi Wang;Wen-Juan Wei;Chao Han;Xiao-Lei Jiang;Ya-Chen Wang;Wei Zou;Jing Liu-.Human umbilical cord-derived mesenchymal stem cells promote repair of neonatal brain injury caused by hypoxia/ischemia in rats)[J].中国神经再生研究（英文版）,2022(11):2518-2525

polypyrimidine,PTBP,Intranasal

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