Human amniotic fluid derived-exosomes alleviate hypoxic encephalopathy by enhancing angiogenesis in neonatal mice after hypoxia

Ping Li; Xiaoxu Lu; Jiajia Hu; Minhui Dai; Jianqin Yan; Huiling Tan; Peilin Yu; Xuliang Chen; Chengliang Zhang

doi:10.1016/j.neulet.2021.136361

Human amniotic fluid derived-exosomes alleviate hypoxic encephalopathy by enhancing angiogenesis in neonatal mice after hypoxia

Neurosci Lett. 2022 Jan 18:768:136361. doi: 10.1016/j.neulet.2021.136361. Epub 2021 Nov 23.

Authors

Ping Li¹, Xiaoxu Lu², Jiajia Hu², Minhui Dai³, Jianqin Yan², Huiling Tan⁴, Peilin Yu⁵, Xuliang Chen⁶, Chengliang Zhang⁷

Affiliations

¹ Department of Obstetrics, Xiangya Hospital, Central South University, Changsha 410008, China; Hunan Engineering Research Center of Early Life Development and Disease Prevention, Changsha 410008, China.
² Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, China.
³ Department of Clinical Dietitian, Xiangya Hospital, Central South University, Changsha 410008, China.
⁴ Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, China; Department of Anesthesiology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410005, China.
⁵ School of Basic Medicine, Third Military Medical University (Army Medical University), Chongqing 400038, China.
⁶ Department of Cardiovascular Surgery, Xiangya Hospital, Central South University, Changsha 410008, China. Electronic address: chenxuliang04@163.com.
⁷ Department of Cardiovascular Surgery, Xiangya Hospital, Central South University, Changsha 410008, China. Electronic address: zhangchengliang@csu.edu.cn.

PMID: 34826550
DOI: 10.1016/j.neulet.2021.136361

Abstract

Neonatal hypoxic encephalopathy is a type of central nervous system dysfunction manifested by high mortality and morbidity. Exosomes play a crucial role in neuroprotection by enhancing angiogenesis. The objective of this study was to investigate the effect of human amniotic fluid-derived exosomes (hAFEXOs) on functional recovery in neonatal hypoxic encephalopathy. The transwell assay, scratch wound healing assay, and tube formation assay were used to evaluate the effect of hAFEXOs on the angiogenesis of human umbilical vein endothelial cells (HUVECs) after oxygen and glucose deprivation (OGD). The angiogenesis of microvascular endothelial cells (MECs) in the cortex was tested in neonatal mice treated with hAFEXOs or phosphate-buffered saline (PBS) after hypoxia. Expressions of hypoxia-inducible factor 1 α (HIF-1α) and vascular endothelial growth factor (VEGF) in the cerebral cortex were also tested by western blot. The Morris Water Maze Test (MWM) was carried out to detect the performance of spatial memory after processing with hAFEXOs or PBS. The results indicated that hAFEXOs favored tubing formation and migration of HUVECs after in vitro OGD. The hAFEXOs also favored the expression of CD31 in neonatal mice following hypoxia. The expressions of both HIF-1α and VEGF were significantly augmented in the cerebral cortex of neonatal mice which were treated with hAFEXOs. Moreover, the MWM test results showed that the performance of the spatial memory was better in the hAFEXO-treated group than in the PBS-treated group. Our study indicates that hAFEXOs alleviated hypoxic encephalopathy and enhanced angiogenesis in neonatal mice after hypoxia. In addition, hAFEXOs promoted migration and tube formation of HUVECs after OGD in vitro. These findings confirm that hAFEXOs show great potential for further studies aimed at developing therapeutic agents for hypoxic encephalopathy.

Keywords: Amniotic fluid; Angiogenesis; Exosomes; Hypoxia; Neonatal hypoxic encephalopathy; Neonatal mice; Neuroprotection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amniotic Fluid
Animals
Animals, Newborn
Exosomes / metabolism*
Human Umbilical Vein Endothelial Cells
Humans
Hypoxia, Brain / pathology*
Mice
Neovascularization, Physiologic / physiology*