14,15-EET Maintains Mitochondrial Homeostasis to Inhibit Neuronal Pyroptosis After Ischemic Stroke

作者：Huixia Geng, Jing Tang, Zhen Li, Yanshuo Zhang, Yanshuo Zhang, Chunting Ye, Yibo Zhang, Yibo Zhang, Xiaohui Li, Yunxia Li, Yanming Wang, Yi Wang, Xinrui Lv, Lai Wang · 发表于：Stroke · 年份：2025 · DOI：10.1161/strokeaha.124.049143 · 被引用次数：11 · 研究领域：Inflammasome and immune disorders、Inflammation biomarkers and pathways、Heme Oxygenase-1 and Carbon Monoxide

BACKGROUND: Neuronal pyroptosis is involved in neuronal cell death and neurological damage after cerebral ischemia-reperfusion. 14,15-Epoxyeicosatrienoic acid (14,15-EET) can reduce neuronal loss induced by cerebral ischemia-reperfusion by regulating mitochondrial biological processes. However, it remains unclear how 14,15-EET regulates mitochondrial homeostasis, inhibits neuronal pyroptosis, and promotes neurological functional recovery after cerebral ischemia-reperfusion. METHODS: Mice with middle cerebral artery occlusion and reperfusion were used as an animal model to study the cerebral ischemia-reperfusion disease. The neurological function of mice was performed at 1, 3, and 5 days to test the therapeutic effects of 14,15-EET. Transmission electron microscope imaging and Nissl staining were used to analyze neuronal morphological structure, mitophagy, and neuronal pyroptosis. Western blot and transcriptome were used to detect the levels of mitophagy and neuronal pyroptosis signaling pathway-related molecules. HT22 cells were used in in vitro studies to detect the mechanism by which 14,15-EET reduces neuronal pyroptosis after oxygen-glucose deprivation/reoxygenation treatment. RESULTS: 14,15-EET treatment reduced cerebral infarct volumes and improved neurological functional recovery in mice after cerebral ischemia-reperfusion. 14,15-EET treatment maintained the morphological structure of neurons in the ischemic penumbra area as well as the dendritic spine density in mice a...