The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury
Yijing Zhao, Tong Li, Zige Jiang, Chengcheng Gai, Shuwen Yu, Danqing Xin, Tingting Li, Dexiang Liu, Zhen Wang
Abstract
Abstract JOURNAL/nrgr/04.03/01300535-202405000-00038/inline-graphic1/v/2023-09-28T063346Z/r/image-tiff We previously showed that hydrogen sulfide (H 2 S) has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice. However, the precise mechanism underlying the role of H 2 S in this situation remains unclear. In this study, we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine, a H 2 S precursor, attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionine β synthase (a major H 2 S synthetase in the brain) in the prefrontal cortex. We also found that an miR-9-5p inhibitor blocked the expression of cystathionine β synthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia. Furthermore, miR-9-5p overexpression increased cystathionine-β-synthase and H 2 S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury. L-cysteine decreased the expression of CXCL11, an miR-9-5p target gene, in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3, FSTL1, SOCS2 and SOCS5, while treatment with an miR-9-5p inhibitor reversed these changes. These findings suggest that H 2 S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoring β-synthase expression, thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.