• Junjie Bai, Shanshan Zeng, Jinjin Zhu, Changchang Fu, Minzhi He, Jianghu Zhu, Shangqing Chen, Xiaoqin Fu, Peijun Li, and Zhenlang Lin.
• Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
• Neuroscience. 2020 Aug 10; 441: 197-208.

AbstractHypoxic-ischemic encephalopathy (HIE) in neonates can lead to severe long-term disabilities including cerebral palsy and brain injury. The small molecule P7C3-A20 has been shown to exert neuroprotective effects in various disorders such as ischemic stroke and neurodegenerative diseases. However, it is unclear whether P7C3-A20 has therapeutic potential for the treatment of HIE, and the relationship between P7C3-A20 and neuronal apoptosis is unknown. To address these questions, the present study investigated whether P7C3-A20 reduces HI injury in vitro using a PC12 cell oxygen-glucose deprivation (OGD) model and in vivo in postnatal day 7 and 14 rats subjected to HI, along with the underlying mechanisms. We found that treatment with P7C3-A20 (40-100 µM) alleviated OGD-induced apoptosis in PC12 cells. In HI model rats, treatment with 5 or 10 mg/kg P7C3-A20 reduced infarct volume; reversed cell loss in the cortex and hippocampus and improved motor function without causing neurotoxicity. The neuroprotective effects were abrogated by treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. These results demonstrate that P7C3-A20 exerts neuroprotection by activating PI3K/protein kinase B/glycogen synthase kinase 3β signaling and can potentially be used to prevent brain injury in neonates following HIE.Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.

15 keywords...

hide…