TXNIP/NLRP3 aggravates global cerebral ischemia-reperfusion injury-induced cognitive decline in mice
Chengjie Yang,
Jing Mo,
Qingmei Liu,
Wei Li,
Ye Chen,
Jianguo Feng,
Jing Jia,
Li Liu,
Yiping Bai,
Jun Zhou
Affiliations
Chengjie Yang
Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China
Jing Mo
Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China
Qingmei Liu
Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China
Wei Li
Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China; Department of Anesthesiology, He Jiang People's Hospital, Luzhou, China
Ye Chen
Department of Traditional Chinese Medicine, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China
Jianguo Feng
Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China
Jing Jia
Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China
Li Liu
Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China
Yiping Bai
Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China
Jun Zhou
Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, Luzhou, China; Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, Southwest Medical University, Luzhou, Sichuan Province, China; Corresponding author. Department of Anesthesiology, The Affiliated Hospital, Southwest Medical University, No.25 Taiping Street, Luzhou, Sichuan Province, 646000, China.
Global cerebral ischemia/reperfusion (GCI/R) injury poses a risk for cognitive decline, with neuroinflammation considered pivotal in this process. This study aimed to unravel the molecular mechanisms underlying GCI/R injury and propose a potential therapeutic strategy for associated cognitive deficits. Utilizing bioinformatics analysis of a public microarray profile (GSE30655 and GSE80681) in cerebral ischemic mice, it was observed that neuroinflammation emerged as a significant gene ontology item, with an increase in the expression of thioredoxin-interacting protein (TXNIP) and NLRP3 genes. Experimental models involving bilateral occlusion of the common carotid arteries in mice revealed that GCI/R induced cognitive impairment, along with a time-dependent increase in TXNIP and NLRP3 levels. Notably, TXNIP knockdown alleviated cognitive dysfunction in mice. Furthermore, the introduction of adeno-associated virus injection with TXNIP knockdown reduced the number of activated microglia, apoptosis neurons, and levels of oxidative stress and inflammatory cytokines in the hippocampus. Collectively, these findings underscore the significance of TXNIP/NLRP3 in the hippocampus in exacerbating cognitive decline due to GCI/R injury, suggesting that TXNIP knockdown holds promise as a therapeutic strategy.
