Carnosol alleviates sevoflurane‑induced cognitive dysfunction by mediating NF‑κB pathway in aged rats

Abstract

Postoperative Cognitive Dysfunction (POCD) is a neurological disorder of unconsciousness due to cognitive regression after surgical anesthesia. However, the specific mechanism has not yet been clarified. Sevoflurane (SEV) is one of the most commonly used anesthetics in clinical practice, and how SEV mediates the generation of POCD is unclear. Carnosol, a natural ingredient, has been reported to have various beneficial effects such as anti-inflammatory, immune enhancement, and so forth, but how it ameliorates SEV-mediated neurotoxicity remains unclear. This study aimed to induce a POCD model in aged rats by SEV and to elucidate how Carnosol ameliorated SEV-mediated neurotoxicity. The effects of Carnosol on the expression of inflammatory factors in rat hippocampus mediated by SEV were determined by enzyme-linked immunoassay and polymerase chain reaction experiments; the effects of Carnosol on the expressions of Iba-1 and glial fibrillary acidic protein after SEV-mediated activation of rat microglia were clarified by immunofluorescence and Western blotting (WB); The effects of Carnosol on SEVmediated neuronal apoptosis were studied by terminal deoxynucleotidyl transferase dUTP nick end labeling and WB; the specific signaling pathways regulated by Carnosol were elucidated by WB. The results showed that Carnosol can improve the cognitive dysfunction and reduce neuroinflammation in aged rats induced by SEV; Carnosol can reduce the activation of microglia and inhibit neuronal apoptosis in aged rats induced by SEV; Carnosol can phosphorylate p65 and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha regulates the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. Carnosol can attenuate SEV-induced neuroinflammation, prevent microglial activation and inhibit neuronal apoptosis by modulating the NF-κB pathway.

Prolonged anesthesia induces neuroinflammation and complement-mediated microglial synaptic elimination involved in neurocognitive dysfunction and anxiety-like behaviors

“…The role of neuroinflammation and the microglia-mediated inflammatory response in inducing SIN has been demonstrated by numerous studies [ 47 – 49 ]. Pathological synaptic pruning mediated by microglia can also be activated in response to inflammation, as reported in West Nile virus infection, sepsis-associated encephalopathy, and lupus [ 38 , 50 , 51 ].…”

Carnosol prevents cardiac remodeling and ventricular arrhythmias in pressure overload‐induced heart failure mice

“…Carnosol, a diterpenoid derived from rosemary, has been demonstrated to possess multiple pharmacological properties. For example, carnosol ameliorates sevoflurane‐induced cognitive dysfunction in aged rats by reducing NF‐κB pathway‐mediated inflammation (Li et al, 2022). Carnosol attenuates high glucose‐induced damage in human retinal endothelial cells by inhibiting oxidative stress through the regulation of the NRF2/HO‐1 pathway (D'Agata et al, 2023).…”

Machine Learning Technology for EEG-Forecast of the Blood–Brain Barrier Leakage and the Activation of the Brain’s Drainage System during Isoflurane Anesthesia

“…There are results that clearly demonstrate a close relationship between the neurotoxicity associated with the development of Alzheimer's disease and anesthesia [12]. Over recent years, a series of studies have begun to focus on anesthesia-induced neurocognitive dysfunction and neuroinflammation [13][14][15].…”