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  • Title: Chikusetsu saponin IVa alleviated sevoflurane-induced neuroinflammation and cognitive impairment by blocking NLRP3/caspase-1 pathway.
    Author: Shao A, Fei J, Feng S, Weng J.
    Journal: Pharmacol Rep; 2020 Aug; 72(4):833-845. PubMed ID: 32124392.
    Abstract:
    BACKGROUND: Neuroinflammation plays a dominant role in the progression of postoperative cognitive dysfunction (POCD). This study was carried out to explore the neuroprotective effect of Chikusetsu saponin IVa (ChIV) against sevoflurane-induced neuroinflammation and cognitive impairment. METHODS: The neuroprotective activity of ChIV against sevoflurane-induced cognitive dysfunction in aged rats was evaluated by Morris water maze, NOR test and Y-maze test, respectively. The expression of NLRP3, ASC and caspase-1, pro-inflammatory cytokines and apoptotic-related protein were detected in the hippocampus and primary neurons using western blot. TUNEL assay and immunohistochemistry staining were applied to assess the apoptotic cell and number of NLRP3-positive cells in the hippocampus. The oxiSelectIn Vitro ROS/RNS assay kit was used to detect the ROS level. The CCK-8 assay was applied to measure the viability of primary neurons. Flow cytometry was carried out to determine cell apoptosis. RESULTS: Pretreatment with ChIV significantly alleviated neurological dysfunction in aged rat exposure to sevoflurane. Mechanistically, ChIV treatment significantly alleviated sevoflurane-induced apoptotic cell and neuroinflammation. Of note, the neuroprotective effect of ChIV against sevoflurane-induced neurotoxicity through blocking NLRP3/caspase-1 pathway. In consistent with in vivo studies, ChIV was also able to repress sevoflurane-induced apoptosis and neuroinflammation in primary neurons. Furthermore, pretreatment with NLRP3/caspase-1 pathway inhibitor (MCC950) significantly augmented the neuroprotective effect of ChIV. CONCLUSION: Our finding confirmed that ChIV provides a neuroprotective effect against sevoflurane-induced neuroinflammation and cognitive impairment by blocking the NLRP3/caspase-1 pathway, which may be an effective strategy for the clinical treatment of elderly patients with POCD induced by anesthesia.
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