title: Glycyrrhizin attenuates isoflurane-induced cognitive deficits in neonatal rats via its anti-inflammatory activity.
abstract: Children exposed to general anesthetics such as isoflurane are maybe at an increased risk of cognitive impairment. Recent studies have indicated that this kind of cognitive decline is associated with neuroinflammation in the hippocampus of neonatal rodents. Glycyrrhizin is a naturally available compound for the treatment of inflammatory and neurodegenerative diseases. We therefore aimed to investigate the effects of glycyrrhizin on the isoflurane-induced cognitive deficits and hippocampal neuroinflammation in the neonatal rats. Seven day-old rats were exposed to 1.8% isoflurane for 4h. Saline and glycyrrhizin solution was injected intraperitoneally 30min prior to isoflurane or control gas exposure. The effects of isoflurane and glycyrrhizin treatment on memory performance were examined using Morris Water Maze (MWM) task. The protein expression of high-mobility group box 1 (HMGB1), NFκB, Bcl-2, Bax and cleaved (active) caspase-3 were determined by Western blot assay. The protein levels of TNF-α and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The combination of ELISA and Western blot results showed that glycyrrhizin attenuated isoflurane-induced increases of pro-inflammatory cytokines (TNF-α and IL-1β) and activation of HMGB1/NFκB signaling pathway in the hippocampus of neonatal rats. Furthermore, glycyrrhizin treatment prevented the deficits in spatial memory induced by neonatal exposure to isoflurane. Consistent with these observations, we found that glycyrrhizin alleviated isoflurane-induced neuroapoptosis and down-regulations of PSD-95 and SNAP-25 in the hippocampus of neonatal rats. These results suggest that glycyrrhizin may be a potential therapeutic agent for developmental neurotoxicity and subsequent cognitive decline induced by neonatal exposure to general anesthetics.
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: L
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: J
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: X
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: alluo@tjh.tjmu.edu.cn.
authors.forename: A
authors.initials: A
authors.lastname: Luo
mesh_terms: D000777:Anesthetics / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007530:Isoflurane / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000777:Anesthetics; D000893:Anti-Inflammatory Agents; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D019695:Glycyrrhizic Acid; D007530:Isoflurane
keywords: HMGB1; NFκB; glycyrrhizin; hippocampus; isoflurane