نبذة مختصرة : Background Ketamine, a commonly used anesthetic, plays a significant role during surgery, but its potential risk for neurotoxicity has drawn considerable attention. Purpose 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 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.
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