HBO Alleviates Neural Stem Cell Pyroptosis via lncRNA-H19/miR-423-5p/NLRP3 Axis and Improves Neurogenesis after Oxygen Glucose Deprivation.

Yuqin Ye,Yongxiang Yang,Shilai Tian,Jiayou Wang,Guanyi Wang,Xiaosheng He,Wei Bai,Yibin Jia,Jinsheng Li,Zhusheng Feng,Shijun Xu

doi:10.1155/2022/9030771

Yuqin Ye, Yongxiang Yang + Show 9 more

Open Access

https://doi.org/10.1155/2022/9030771

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Abstract

Due to the limited neurogenesis capacity, there has been a big challenge in better recovery from neurological dysfunction caused by stroke for a long time. Neural stem cell (NSC) programmed death is one of the unfavorable factors for neural regeneration after stroke. The types of death such as apoptosis and necroptosis have been deeply investigated while the pyroptosis of NSCs is not quite understood. Although it is well accepted that hyperbaric oxygen (HBO) alleviates the oxygen-glucose deprivation (OGD) injury after stroke and reduces programmed death of NSCs, whether NSC pyroptosis is involved in this process is still unknown. Therefore, this study is aimed at studying the potential effect of HBO treatment on NSC pyroptosis following OGD exposure, as well as its influence on NSC proliferation and differentiation in vitro. The results revealed that OGD increased NOD-like receptor protein 3 (NLRP3) expression to induce the pyroptotic death of NSCs, which was rescued by HBO treatment. And the upregulated lncRNA-H19 functioned as a molecular sponge of miR-423-5p to target NLRP3 for NSC pyroptosis following OGD. Most importantly, it was confirmed that HBO exerted protection of NSCs against pyroptosis by inhibiting lncRNA-H19/miR-423-5p/NLRP3 axis. Moreover, HBO restraint of lncRNA-H19-associated pyroptosis benefited the proliferation and neuronal differentiation of NSCs. It was concluded that HBO attenuated NSC pyroptosis via lncRNA-H19/miR-423-5p/NLRP3 axis and enhanced neurogenesis following OGD. The findings provide new insight into NSC programmed death and enlighten therapeutic strategy after stroke.

Highlights

Ischemic stroke is a leading cerebral vascular event associated with high morbidity, disability, and mortality in central nervous system
In the following experiments, the pressure of 2.0 ATA was employed to investigate the effect of hyperbaric oxygen (HBO) treatment on Neural stem cell (NSC) pyroptosis and neurogenesis after oxygen-glucose deprivation (OGD)
To further validate whether Long noncoding RNA (lncRNA)-H19/miR-423-5p/NOD-like receptor protein 3 (NLRP3) axis was responsible for NSC pyroptosis induced by OGD, cells were divided into six groups: Con group, OGD group, siRNA-NC transfection and OGD exposure group (OGD+siRNA-NC group), siRNA-H19 transfection and OGD exposure group (OGD +siRNA-H19 group), siRNA-H19 and miR-NC inhibitor cotransfection and OGD exposure group (OGD+siRNAH19+miR-NC inhibitor group), and siRNA-H19 and miR423-5p inhibitor cotransfection and OGD exposure group (OGD+siRNA-H19+miR-423-5p inhibitor group)

Summary

Introduction

Ischemic stroke is a leading cerebral vascular event associated with high morbidity, disability, and mortality in central nervous system. Neural stem cells (NSCs), located in the subgranular zone of adult hippocampus, can proliferate and differentiate into various kinds of cells in order to repair the injured brain [1]. It has been documented that ischemic injury activates hippocampal NSCs to generate newborn neurons for neurogenesis, whereas the amount is very limited and not enough to replenish the damaged cells for neurological function restoration [2]. One of the main reasons is that in the case of oxygen-glucose deprivation (OGD) after stroke, a host of NSC programmed deaths occur before neurogenesis begins. A lot of studies have elucidated the types of programmed death such as apoptosis and necroptosis in response to OGD exposure, little is known about NSC pyroptosis [3, 4].

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