Remifentanil Ameliorates Lipopolysaccharide-Induced Neuroinflammation by Regulating the Phosphatidylinositol 3-Kinase/Serine-Threonine Protein Kinase/Hypoxia-Inducible Factor 1 Alpha Pathway

There has been scarce research on the potential neuroprotective effects of remifentanil (REM) in septic individuals. We aimed to investigate the role and underlying mechanism of REM in LPS-induced neuroinflammation. Thirty-two rats were randomly divided to control, lipopolysaccharide (LPS), LPS + REM, and REM groups. Depending on the group, 4 h after intraperitoneal administration of LPS or saline, REM or saline was infused intravenously for 40 min. Following the sacrification, blood samples and brain tissues were collected for analysis. Brain tissues (prefrontal cortex, cerebellum, and hippocampus) were stained with hematoxylin and eosin, caspase-3 (Cas-3), and tumor necrosis factor alpha (TNF-alpha). Quantitative reverse transcription-polymerase chain reaction analysis was used to detect claudin-5 (CLDN5), zonula occludens-1 (ZO-1), phosphatidylinositol 3-kinase (PI3K), serine-threonine protein kinase (AKT), and hypoxia-inducible factor 1 alpha (HIF-1 alpha) gene expression levels. Histopathologic and immunohistochemical analyses showed that REM treatment improved LPS-induced histological changes. REM does not reduce TOS and OSI levels or increase TAS levels, suggesting that it is ineffective through oxidative stress. LPS-induced changes in gene expression levels (PI3K, AKT, HIF-1 alpha, and CLDN5) were also reversed by REM. REM was found to prevent neuroinflammation, and apoptosis by restoring blood-brain barrier, and regulating the PI3K/AKT/HIF-1 alpha pathway. These findings suggest that REM is protective against neuroinflammation.