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Macrophage migration inhibitory factor in the mouse hippocampus promotes neuroinflammation and cognitive dysfunction
Lian Zeng1, Peng-Chao Hu2, Yu Zhang2
1Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Abstract:
Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia and surgery, particularly in elderly individuals. Although progress has been made in understanding its causes, the modulatory mechanism of neuroinflammation in POCD is still not fully understood. Macrophage migration inhibitory factor (MIF) has been demonstrated to be crucial in neuroinflammation and neuronal damage, but its role in POCD remains unclear. This study aimed to explore the role of MIF in neuroinflammation and cognitive impairment following anesthesia and surgery. We revealed that there is a notable cognitive deficit in mice following anesthesia and surgery, accompanied by exacerbated neuroinflammation. Which was marked by elevated levels of pro-inflammatory cytokines and the activation of microglia and astrocytes in mice hippocampus. Notably, there was a pronounced upregulation of MIF expression in the serum and hippocampus, particularly within neurons and microglia, following anesthesia and surgery. MIF deficiency improved cognitive impairment and inhibited neuroinflammation, as well as decreasing release of pro-inflammatory cytokines, reducing activation of microglia and astrocytes, and performing the preservation of dendritic spine structure and neuronal integrity. This finding implies that MIF plays a crucial role in mediating neuroinflammation and cognitive dysfunction following anesthesia and surgery, and targeting MIF-mediated neuroinflammation may offer a novel strategy to POCD.
Insights
Macrophage migration inhibitory factor (MIF) exacerbates neuroinflammation and cognitive deficits after surgery. Targeting MIF may offer a new strategy for treating postoperative cognitive dysfunction (POCD).
Area of Science:
- Neuroscience
- Immunology
- Anesthesiology
Background:
- Postoperative cognitive dysfunction (POCD) is a common complication, especially in the elderly.
- The role of neuroinflammation in POCD is not fully understood.
- Macrophage migration inhibitory factor (MIF) is implicated in neuroinflammation but its role in POCD is unclear.
Purpose of the Study:
- To investigate the role of MIF in neuroinflammation and cognitive impairment following anesthesia and surgery.
Main Methods:
- Mice underwent anesthesia and surgery to assess cognitive function and neuroinflammation.
- MIF expression levels were measured in serum and hippocampus.
- MIF-deficient mice were used to evaluate the impact of MIF deficiency.
Main Results:
- Anesthesia and surgery led to cognitive deficits and increased neuroinflammation, characterized by elevated pro-inflammatory cytokines and glial cell activation.
- MIF expression was significantly upregulated in serum and hippocampus post-surgery.
- MIF deficiency ameliorated cognitive impairment, reduced neuroinflammation, and preserved neuronal integrity.
Conclusions:
- MIF plays a critical role in mediating neuroinflammation and cognitive dysfunction after anesthesia and surgery.
- Targeting MIF-mediated neuroinflammation presents a potential therapeutic strategy for POCD.
