• Liu-Lin Xiong, Lu-Lu Xue, Ya Jiang, Zheng Ma, Yuan Jin, You-Cui Wang, Yang-Yang Wang, Qing-Jie Xia, Ying Zhang, Qiao Hu, Jia Liu, and Ting-Hua Wang.
• Institute of Neurological Disease, Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University, 610041 Chengdu, China; National Traditional Chinese Medicine Clinical Research Base and Western Medicine Translational Medicine Research Center, Department of Anesthesiology, Department of Cardiovascular Disease, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, 646000 Luzhou, Sichuan, China; School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide 5000, South Australia, Australia.
• Brain Res. 2019 Sep 15; 1719: 77-88.

AbstractNeonatal hypoxic-ischemic encephalopathy (HIE) always results in severe neurologic dysfunction, nevertheless effective treatments are limited and the underlying mechanism also remains unclear. In this study, we firstly established the neonatal HIE model in the postnatal day 7 SD rats, Zea-Longa score and TTC staining were employed to assess the neurological behavior and infarct volume of the brain after cerebral hypoxia-ischemia (HI). Afterwards, protein chip was adopted to detect the differential proteins in the right cortex, hippocampus and lung, ultimately, PDGF was noticed. Then, immunohistochemistry, immunofluorescence double staining of NeuN/PDGF, and western blot were used to validate the expression level of PDGF in the cortex and hippocampus at 6 hours (h), 12 h and 24 h after HI. To determine the role of PDGF, the primary cortical neurons were prepared and performed PDGF shRNA administration. The results showed that HIE induced a severe behavioral dysfunction and brain infarction in neonatal rats, and the expression of PDGF in right cortex and hippocampus was remarkably increased after HI. Whereas, suppressing PDGF resulted in a significant loss of neurons and inhibition of neurite growth. Moreover, the protein level of P-PI3K and P-AKT signaling pathways were largely decreased following PDGF-shRNA application in the cortical neurons. In conclusion, PDGF suppression aggravated neuronal dysfunction, and the underlying mechanism is associated with inhibiting the phosphorylation of P-PI3K and P-AKT. Together, PDGF regulating PI3K and AKT may be an important panel in HIE events and therefore may provide possible strategy for the treatment of HIE in future clinic trail.Copyright © 2019. Published by Elsevier B.V.

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