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Neuroprotective Effects of Simvastatin against Isoflurane-Induced Neurotoxicity in Primary Cortical Neurons Involvement of PI3K-Akt Pathway
Vol 37, Issue 1, 2023
Abstract
Background: During brain development, isoflurane exposure-induced brain neuronal damage may be associated with cognitive impairment in adulthood. Simvastatin has a particular neuroprotective effect. However, it is unclear whether simvastatin protects cortical neurons exposed to isoflurane. The aim of this study was to explore the action of simvastatin on cortical neurons exposed to isoflurane and establish the mechanism of this action. Methods: An in vitro model of free primary cultured Sprague-Dawley rat neurons was constructed. Neuronal Class III β-Tubulin (Tuj1) staining was used to identify primary neurons. Cell Counting Kit-8 (CCK-8) assay was used to test neuron cell viability. Propidium Iodide (PI)/Hoechst 33342 staining was used to determine the levels of apoptosis in the neurons and western blot was used to check the caspase-3, B-cell lymphoma-2 (Bcl-2), protein kinase B (Akt) and p-Akt protein expression levels in cortical neurons. Results: Exposure to isoflurane significantly increased apoptosis during neuronal development. Cortical neurons exposed to isoflurane showed significantly decreased Bcl-2 and p-Akt expression and increased caspase-3 expression. Simvastatin significantly reversed these changes. PI3K (phosphoinositide 3-kinase) inhibitor LY294002 significantly inhibited the reversal of isoflurane-induced neurotoxicity by simvastatin. Conclusions: Simvastatin pretreatment protects neurons from isoflurane-induced neurotoxicity in vitro. The phosphoinositide 3-kinase (PI3K)/Akt pathway participates in inhibiting the effect of simvastatin on isoflurane-induced neuronal apoptosis.
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Copyright (c) 2023 Xi-juan Zhao, Kui Wang, Rong Li, Yang Lu, Pan Lu, Pei Fan, Yu-ying Lv, Xin-lin Chen, Hao-zheng Yuan
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Medical Genetics, University of Torino Medical School, Italy

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy