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

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.

The exo‐microRNA (miRNA) signaling pathways in pathogenesis and treatment of stroke diseases: Emphasize on mesenchymal stem cells (MSCs)

“…The NLRP3‐dependent pyroptosis signaling was silenced as a result of the inhibition of the lncRNA‐H19/miR‐423‐5p/NLRP3 axis, which was the underlying mechanism. The findings increased our comprehension of NSC pyroptosis and offered a fresh idea for developing a treatment plan for stroke‐induced neuronal regeneration 139 . LncRNA‐ZFAS1 overexpression reduced m6A levels of Drp1 and undid the exosomal KLF4 silencing's positive effects on mitochondrial damage and the imbalance of mitochondrial dynamics.…”

Human Breast Milk microRNAs, Potential Players in the Regulation of Nervous System

“…This results in an impairment of neuronal function in MS [ 73 ]. Downregulation in preterm versus term mature milk is the same way for miR-423-5p, which is known that acts repressing neurogenesis [ 74 ], and also tissue fraction of major depressive disorder (MDD) subjects in the synaptic fraction is upregulated [ 75 ]. On the other hand, miR-451a, which has lower levels in late preterm than in term mature milk, was downregulated in AD cerebrospinal fluid (CSF) [ 65 ].…”

HSP90-Dependent Upregulation of EZH2 Promotes Hypoxia/Reoxygenation-Induced Pyroptosis by Inhibiting miR-22 in Endothelial Cells

“…It has been demonstrated that miRNAs act as key regulators of pyroptosis by modulating the expression levels of key genes in pyroptosis. [44][45][46] EZH2 was shown to suppress the expression of microRNAs under oxidative stress, such as miR-139, 47 miR-34a 35 and miR-451. 48 Recently, miR-22 was reported to promote endothelial cell pyroptosis.…”