Fei Wang, Wenji Zhou, Liqing Huang, Li Sun, Lujun Deng, Liping Li
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引用次数: 0
Abstract
Cerebral ischemia-reperfusion (I/R) injury represents a debilitating neurological disorder with significant morbidity. Artesunate, a water-soluble hemisuccinate derivative, has emerged as a potential therapeutic agent for cerebral I/R injury. Our investigation endeavors to assess the efficacy of artesunate in this context while elucidating its mechanisms of action. We established the middle cerebral artery occlusion/refusion (MACO) rat model and oxygen-glucose deprivation/reperfusion (OGD/R)-stimulated PC12 cells model. Mitophagy was analyzed by transmission electron microscope, mitochondrial membrane potential detection, western blotting, and real-time quantitative polymerase chain reaction (RT-qPCR). The underlying mechanism was investigated by cell viability, flow cytometry, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The results suggested that artesunate inhibited apoptosis and excessive mitophagy. Mechanically, artesunate regulated FUN14 domain containing 1 (FUNDC1)-mediated mitophagy via the AMPK (AMP-activated protein kinase)-mTOR (mechanistic target of rapamycin)-TFEB (transcription factor EB) signaling pathway. Additionally, artemether reduced the infarct size in MCAO rats, inhibited neurological dysfunction, and enhanced memory performance. In summary, our data revealed a novel mechanism whereby artesunate suppresses apoptosis by inhibiting excessive mitophagy. These findings offered a new promising therapy for cerebral I/R injury.
期刊介绍:
The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.