Effects of remimazolam and surgery on cognition in a tibia fracture mouse model.

BACKGROUND

To investigate the effects of remimazolam and surgery on cognitive function and neuropathology.

METHODS

We performed intramedullary pin fixation of tibial fractures in wild-type male (12-13-week-old) C57BL/6J mice under intraperitoneal anesthesia with remimazolam. Age-matched wild-type control mice received either saline or remimazolam without surgery. Training was performed 1 h before surgery, and the open field test was performed on the third postoperative day, in addition to trace fear conditioning on the third versus the seventh day and the Y maze test on the fourth versus the eighth day. Phosphorylated tau (P-TAU) protein levels in hippocampal tissue, microglial activation, dendritic spine density in neuronal cells, and interleukin-6 (IL-6) levels were determined.

RESULTS

We detected no significant differences in locomotor ability among the three groups in the open field test on the third postoperative day; however, on the conditioned fear test or in the Y-maze, the cognitive related performance of the mice in the surgery group was significantly worse than that of the control group and the remimazolam group. However, there were no differences among the three groups in the behavioural experiments on the seventh and eighth days. In addition, mice in the surgery group had higher levels of P-TAU in their hippocampal tissue, more microglial activation, more significant changes in neuronal dendritic spine density, and higher levels of IL-6 in their hippocampal tissue compared with mice in the other two groups.

CONCLUSIONS

The cognitive dysfunction and neuropathological changes produced by remimazolam-based surgery are mainly of surgical origin and are not related to the use of remimazolam, a general anesthetic agent.