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Updated: Jun 8, 2025
A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration
Published on: February 27, 2018
Effects of remimazolam and surgery on cognition in a tibia fracture mouse model
Jianhui Zhao1, Tingting Yu1, Ruilin He1
1Department of Anesthesiology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
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.
Insights
Surgery, not remimazolam anesthesia, impairs cognitive function and causes neuropathology. Post-operative cognitive deficits and brain changes in mice were linked to the surgical procedure itself.
Area of Science:
- Anesthesiology
- Neuroscience
- Surgical Research
Background:
- Investigating the impact of remimazolam and surgical procedures on cognitive function and neuropathology is crucial.
- Understanding the specific contributions of anesthesia versus surgical trauma to post-operative neurological changes is essential.
Purpose of the Study:
- To differentiate the effects of remimazolam anesthesia from surgical intervention on cognitive performance and neuropathological markers in a mouse model.
- To assess potential cognitive deficits and neuroinflammation induced by remimazolam-based surgery.
Main Methods:
- Intramedullary pin fixation of tibial fractures was performed in mice under remimazolam anesthesia.
- Control groups received saline or remimazolam without surgery; cognitive tests (open field, fear conditioning, Y-maze) and neuropathological analyses (P-TAU, microglial activation, dendritic spine density, IL-6) were conducted.
Main Results:
- Surgical intervention significantly worsened cognitive performance in fear conditioning and Y-maze tests compared to control and remimazolam-only groups.
- Mice undergoing surgery exhibited increased phosphorylated tau (P-TAU) levels, microglial activation, altered dendritic spine density, and elevated IL-6 in hippocampal tissue.
- No significant differences in locomotor activity or long-term cognitive performance (7th/8th day tests) were observed among groups.
Conclusions:
- Cognitive dysfunction and neuropathological changes observed following remimazolam-based surgery are primarily attributable to the surgical procedure itself.
- Remimazolam, as a general anesthetic agent, does not appear to be the primary cause of the observed cognitive and neuropathological impairments.
