Objective To investigate the effects of combined sevoflurane and propofol anesthesia on postoperative cognitive dysfunction (POCD) and neural synapses in aged rats with hip fracture.

Methods An elderly rat model of hip fracture was established via surgical intervention. Successfully modeled rats were randomly assigned to six groups (n = 15/group): a Sham + Pure Oxygen group (incision only + 3-hour pure oxygen inhalation), a Sham + Combined Anesthesia group (incision only + 3-hour inhalation of 1.7% sevoflurane combined with 20 mg/kg propofol), a Fracture + Pure Oxygen group (3-hour pure oxygen inhalation), a Fracture + Sevoflurane group (3-hour inhalation of 3% sevoflurane), a Fracture + Propofol group (3-hour tail vein infusion of 40 mg/kg propofol), and a Fracture + Combined Anesthesia group (3-hour inhalation of 1.7% sevoflurane combined with 20 mg/kg propofol). Twenty-four hours after the final anesthesia intervention, cognitive function was assessed via open-field test and novel object recognition (NOR) test. HE and TUNEL staining were used to observe histopathological changes and neuronal apoptosis in the hippocampus. Golgi staining was used to observe dendritic spine density in hippocampal neurons. Immunohistochemistry was used to detect synapsin 1 (Syn1) expression intensity in hippocampal tissue. Western blotting was used to detect the protein expression profiling of PSD95, Syn1, BDNF, TrkB, p-CREB, and CREB.

Results No significant differences were observed among the Sham + Pure Oxygen group, Sham + Combined Anesthesia group, and Fracture + Pure Oxygen group in terms of neuronal histopathological damage, total movement distance, central area residence time, novel object discrimination index, neuronal apoptosis rate, dendritic spine density, Syn1 expression intensity, or protein expression levels of Syn1, PSD95, BDNF, TrkB, and p-CREB (all P ＞ 0.05). In contrast, the Fracture + Sevoflurane group and Fracture + Propofol group exhibited disorganized neuronal arrangement, blurred neuronal structures, reduced neuronal quantity, and significantly decreased total movement distance, central area residence time, novel object discrimination index, dendritic spine density, Syn1 expression intensity, and protein expression levels of Syn1, PSD95, BDNF, TrkB, and p-CREB compared to the Fracture + Pure Oxygen group (all P ＜ 0.05). These groups also showed a significantly elevated neuronal apoptosis rate (P ＜ 0.05). Compared to the Fracture + Sevoflurane group and Fracture + Propofol group, the Fracture + Combined Anesthesia group demonstrated significantly increased total movement distance, central area residence time, novel object discrimination index, dendritic spine density, Syn1 expression intensity, and protein expression levels of Syn1, BDNF, TrkB, and p-CREB (all P ＜ 0.05), and a reduced neuronal apoptosis rate (P ＜ 0.05).

Conclusions Combined sevoflurane and propofol anesthesia effectively ameliorates POCD in aged rats with hip fracture, inhibit hippocampal histopathological damage and neuronal apoptosis, and improve synaptic function. The underlying mechanism may involve activation of the BDNF/TrkB/CREB signaling pathway.