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Updated: Jul 11, 2025
A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration
Published on: February 27, 2018
Inhibition of MMP-2 and MMP-9 attenuates surgery-induced cognitive impairment in aged mice
Yiqin Ji1, Wanbo Huang2, Yijun Chen1
1Department of Anesthesiology, The First Affiliated Hospital of Ningbo University, Ningbo 315010, Zhejiang, China.
Background:
The inhibition of matrix metalloproteinases (MMPs) has shown potential in the treatment of various neurodegenerative diseases, and perioperative neurocognitive disorders (PND) is accompanied by the increased expression of MMP-2 and MMP-9 in the hippocampus. However, the effect of inhibiting MMP-2 and MMP-9 on PND is not clear. In this study we aimed to evaluate the effects of inhibiting MMP-2 and MMP-9 on cognitive function in the aged mice after surgery, in order to find a possible target for the prevention and treatment of PND METHODS: In this study, 14-month-old C57BL/6 mice were used to establish a PND model by tibial fracture surgery and sevoflurane anesthesia. Three days later, part of the mice were subjected to cognitive assessment and the other was sacrificed for biochemical analysis. We used the Novel object recognition test and Fear conditioning test to evaluate the postoperative cognitive function of mice. The expression of mmp-2 and MMP-9 was detected by western blotting. We also examined the expression of claudin-5 and occludin using Western blotting, and the activation of microglia and astrocytes using immunofluorescence.
Results:
The results showed that surgery increased the expression of MMP-2 and MMP-9 in the hippocampus of mice, accompanied by cognitive impairment, decreased expression of claudin-5 and occludin, and increased activation of microglia and astrocytes. However, inhibition of MMP-2 and MMP-9 expression by SB-3CT reversed these changes.
Conclusions:
Our study shows that inhibition of MMP-2 and MMP-9 alleviates anesthesia/surgery-induced cognitive decline by increasing BBB integrity and inhibiting glial cell activation.
Insights
Inhibiting matrix metalloproteinases (MMPs), specifically MMP-2 and MMP-9, can help prevent cognitive decline after surgery and anesthesia. This approach improves brain barrier integrity and reduces inflammation, offering a potential treatment for perioperative neurocognitive disorders (PND).
Area of Science:
- Neuroscience
- Pharmacology
- Gerontology
Background:
- Perioperative neurocognitive disorders (PND) are linked to increased matrix metalloproteinase (MMP) expression in the hippocampus.
- The specific role of inhibiting MMP-2 and MMP-9 in PND remains unclear.
- This study investigates MMP inhibition as a potential therapeutic strategy for PND.
Purpose of the Study:
- To evaluate the effect of inhibiting MMP-2 and MMP-9 on cognitive function in aged mice following surgery.
- To identify potential therapeutic targets for the prevention and treatment of PND.
Main Methods:
- A PND model was established in 14-month-old C57BL/6 mice using tibial fracture surgery and sevoflurane anesthesia.
- Cognitive function was assessed using the Novel Object Recognition and Fear Conditioning tests.
- MMP-2, MMP-9, claudin-5, and occludin expression were analyzed via Western blotting; glial cell activation was assessed using immunofluorescence.
Main Results:
- Surgery induced cognitive impairment, increased hippocampal MMP-2 and MMP-9 expression, decreased claudin-5 and occludin levels, and elevated microglial and astrocyte activation.
- Treatment with SB-3CT, an MMP inhibitor, reversed these surgery-induced changes.
- Inhibition of MMP-2 and MMP-9 demonstrated a protective effect against PND.
Conclusions:
- Inhibition of MMP-2 and MMP-9 alleviates surgery- and anesthesia-induced cognitive decline.
- This neuroprotective effect is mediated by enhanced blood-brain barrier (BBB) integrity and suppressed glial cell activation.
- Targeting MMP-2 and MMP-9 presents a promising therapeutic avenue for PND.
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