2021
DOI: 10.3389/fnagi.2020.620946
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Atorvastatin Attenuates Isoflurane-Induced Activation of ROS-p38MAPK/ATF2 Pathway, Neuronal Degeneration, and Cognitive Impairment of the Aged Mice

Abstract: Isoflurane, a widely used volatile anesthetic, induces neuronal apoptosis and memory impairments in various animal models. However, the potential mechanisms and effective pharmacologic agents are still not fully understood. The p38MAPK/ATF-2 pathway has been proved to regulate neuronal cell survival and inflammation. Besides, atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, exerts neuroprotective effects. Thus, this study aimed to explore the influence of atorvastatin on isoflurane-in… Show more

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Cited by 15 publications
(12 citation statements)
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“…The length of use in mice might not exactly mimic the time used in humans in consideration of their length of life respectively. In this study, 6 h of isoflurane exposure was used based on previous research in a cognitive impairment mouse model induced by lengthy isoflurane inhalation [7] , [50] , [51] . Our previous study also has proved that 6 h isoflurane exposure could induce a significant cognitive decline in adult mice [10] , [11] , [52] .…”
Section: Discussionmentioning
confidence: 99%
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“…The length of use in mice might not exactly mimic the time used in humans in consideration of their length of life respectively. In this study, 6 h of isoflurane exposure was used based on previous research in a cognitive impairment mouse model induced by lengthy isoflurane inhalation [7] , [50] , [51] . Our previous study also has proved that 6 h isoflurane exposure could induce a significant cognitive decline in adult mice [10] , [11] , [52] .…”
Section: Discussionmentioning
confidence: 99%
“…Our previous study also has proved that 6 h isoflurane exposure could induce a significant cognitive decline in adult mice [10] , [11] , [52] . In addition, different to 2 h isoflurane exposure which can’t elicit the activation of BV-2 cells or primary microglial cells [9] , 6 h isoflurane or sevoflurane treatment can directly increase the expression level and transcription activity of nuclear factor kappa-B as well as the production of pro-inflammatory cytokines in H4 human neuroglioma cells, mouse primary microglia, and BV2 cells [7] , [51] , [53] . All in all, prolonged sub-MAC isoflurane inhalation can induce remarkable neuroinflammation and cognitive decline by promoting microglia and astrocyte activation in adults and should be fully considered for the use of inhaled anesthetics in prolonged sedation.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…In a male newborn piglet, exposure to isoflurane results in the activation of microglia and causes significant alternations to the genes mediating memory formation and recall [ 21 ]. Isoflurane induces cognitive impairment of aged mice and induces inflammation and oxidative stress in BV2 cells through the ROS-p38MAPK/ATF2 pathway [ 22 ]. Isoflurane induces the increased protein levels of TNF-α, IL-1β, interferon (IFN)-γ, and microglia marker Iba-1 [ 23 ].…”
Section: Discussionmentioning
confidence: 99%
“…After 1 week of adaptation, 80 mice were randomly divided into four groups: control group, isoflurane group (ISO), ISO + 30 mg/kg CGA group, and ISO + 60 mg/kg CGA (N = 20 in each group). Chlorogenic acid (Sigma‐Aldrich, purity 95%; St. Louis, MO, USA) was dissolved in sterile saline and administered orally by gavage once daily for 7 days, while the normal group was given sterile saline (Liu et al, 2021). On day 8, the mice were exposed to 1.5% ISO (Nanjing Jiancheng Bioengineering Institute), mixed with 100% O 2 for 4 h, and the mice in the control group received 100% O 2 of 1.5 L/min for 4 h in an identical chamber (X.‐m.…”
Section: Methodsmentioning
confidence: 99%