Functional Recovery and Cellular Damage Mechanism of Mesoporous Silica Nanoparticles/Chitosan Solution/ Methylprednisolone-collagen on Nerve Injury Caused by Ketamine Overdose

Background: Ketamine, a commonly used anesthetic, plays a significant role during surgery, but its potential risk for neurotoxicity has drawn considerable attention. Objectives: This study was aimed to investigate the effects of methylprednisolone (MP) loaded onto mesoporous silica nanoparticles (MSN) based on chitosan solution (CS) in ketamine overdose-induced neurotoxicity, focusing on its effects on neural function recovery and cellular damage. The goal was to provide new strategies and a theoretical foundation for the treatment of neuro injury. Materials and Methods: MSN/CS/MP collagen (MP col) was prepared using the sol-gel method and characterized for its drug loading capacity, encapsulation efficiency, and release performance. Forty Sprague-Dawley rats were divided into five groups: control group (CG), ketamine group (KG), low concentration group (LG), medium concentration group (MG), and high concentration group (HG)). Except for the CG, the remaining groups were subjected to a ketamine-induced nerve injury model and received different concentrations of MSN/CS/MP col injections. Subsequently, the expression of key hippocampal proteins, apoptosis levels, and spatial memory were evaluated. Results: The drug loading capacity of MSN/CS/MP col was 23.01 ± 0.51%, and the encapsulation efficiency was 95.24 ± 2.36%. Compared to CG, the escape latency was prolonged and exploratory time was shortened in the KG, LG, MG, and HG. The levels of p-Akt/Akt, Bcl-2, and PSD-95 were reduced, while the levels of Cas-3/Cas-3 and Bax were increased in the KG. The density of apoptotic cells was elevated in the KG and HG (p<0.05). Conclusion: MSN/CS/MP col promotes functional recovery by regulating key proteins and reducing neuronal apoptosis, offering a novel approach for the treatment of nerve injury.