Ganglioside GM1 Alleviates Propofol-Induced Pyroptosis in the Hippocampus of Developing Rats via the PI3K/AKT/NF-κB Signaling Cascade

In pediatric and intensive care units, propofol is widely used for general anesthesia and sedation procedures as a short-acting anesthetic. Multiple studies have revealed that propofol causes hippocampal injury and cognitive dysfunction in developing Animals. As is known, GM1, a type of ganglioside, plays a crucial role in promoting nervous system development. Consequently, this study explored whether GM1 mitigated neurological injury caused by propofol during developmental stages and investigated its underlying mechanisms. Seven-day-old SD rats or PC12 cells were used in this study for histopathological analyses, a Morris water maze test, a Lactate Dehydrogenase release assay, Western blotting, and an ELISA. Furthermore, LY294002 was employed to explore the potential neuroprotective effect of GM1 via the PI3K/Akt signaling cascade. The results indicated that GM1 exerted a protective effect against hippocampal morphological damage and Pyroptosis as well as behavioral abnormalities following propofol exposure by increasing p-PI3K and p-AKT expression while decreasing p-p65 expression in developing rats. Nevertheless, the inhibitor LY294002, which targets the PI3K/Akt cascade, attenuated the beneficial effects of GM1. Our study provides evidence that GM1 confers neuroprotection and attenuates propofol-induced developmental neurotoxicity, potentially involving the PI3K/Akt/NF-κB signaling cascade.

GM1; PI3K/AKT/NF-κB signaling; developing rats; neuroinflammation; propofol; pyroptosis.