• Neuroscience · Aug 2023

    Neuroprotective Effects of Vinpocetine against Ischemia-Reperfusion Injury via Inhibiting NLRP3 Inflammasome Signaling Pathway.

    • Boru Hou, Donghai Li, Dengfeng Wang, Cheng Jiang, Gang Wang, Dong Wang, Guizhong Yan, Xiumei Guo, Lixia Zhao, Zhuangzhuang Wan, Chenlong Fan, Wencheng Cao, and Haijun Ren.
    • Department of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, China. Electronic address: friend7412@126.com.
    • Neuroscience. 2023 Aug 21; 526: 748474-84.

    AbstractIschemic stroke is one of the main causes of serious disability and death worldwide. NLRP3 inflammasome is an intracellular pattern recognition receptor composed of polyprotein complex, which participates in mediating a series of inflammatory responses and is considered as a potential target for the treatment of ischemic stroke. Vinpocetine, a derivative of vincamine, has been widely used in the prevention and treatment of ischemic stroke. However, the therapeutic mechanism of vinpocetine is not clear, and its effect on NLRP3 inflammasome remains to be determined. In this study, we used the mouse model of transient middle cerebral artery occlusion (tMCAO) to simulate the occurrence of ischemic stroke. Different doses of vinpocetine (5, 10, 15 mg/kg/d) were injected intraperitoneally for 3 days after ischemia-reperfusion in mice. The effects of different doses of vinpocetine on the degree of ischemia-reperfusion injury in mice were observed by TTC staining and modified neurological severity score scale, and the optimal dose was determined. Then, based on this optimal dose, we observed the effects of vinpocetine on apoptosis, microglial proliferation and NLRP3 inflammasome. In addition, we compared the effects of vinpocetine and MCC950 (a specific inhibitor of NLRP3 inflammasome) on NLRP3 inflammasome. Our results show that vinpocetine can effectively reduce the infarct volume and promote the recovery of behavioral function in stroke mice, and the maximal beneficial effects were observed at the dose of 10 mg/kg/d. Vinpocetine can effectively inhibit the apoptosis of peri-infarct neurons, promote the expression of Bcl-2, inhibit the expression of Bax and Cleaved Caspase-3, and reduce the proliferation of peri-infarct microglia. In addition, vinpocetine, like MCC950, can reduce the expression of NLRP3 inflammasome. Therefore, vinpocetine can effectively alleviate the ischemia-reperfusion injury in mice, and the inhibition of NLRP3 inflammasome may be an important therapeutic mechanism of vinpocetine.Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

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