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image of Mechanism of Pyroptosis in Postoperative Cognitive Dysfunction Rats and α7-nicotinic Receptor Agonist Regulating NLRP3 Inflammasome Activation

Abstract

Background

This study investigates the efficacy of α7-nicotinic acetylcholine receptor (α7nAChR) agonists in mitigating postoperative cognitive dysfunction (POCD) in a rat model. This investigation aimed to elucidate the therapeutic potential of α7nAChR agonists in modulating neuroinflammatory pathways to improve cognitive outcomes post-surgery.

Objective

Serum levels of pro-inflammatory cytokines IL-1β and IL-18 were measured as markers of systemic inflammation, while the expression levels of NLRP3 mRNA were quantified to evaluate pyroptosis and NLRP3 inflammasome activation.

Methods

Adult male Sprague-Dawley rats were divided into control (no surgery), POCD (surgery-induced), and POCD treated with an α7nAChR agonist. Cognitive function was assessed using the Morris Water Maze (MWM) and Novel Object Recognition (NOR) tests.

Results

The results showed a notable cognitive impairment in the group with POCD, as shown by increased escape latency noted in the MWM test and decreased discrimination index in the NOR test, while controls had no change. However, treatment with the α7nAChR agonist led to a significant improvement in cognitive performance among the POCD rats such that it closely matched those of the controls. Furthermore, the POCD group exhibited elevated serum levels of IL-1β and IL-18 and increased expression of pyroptosis-related markers, indicating enhanced neuroinflammation and inflammasome activation.

Conclusion

These findings highlighted the therapeutic efficacy of α7nAChR agonists in mitigating neuroinflammation and improving cognitive outcomes post-surgery. Our study supports the potential of targeting the cholinergic anti-inflammatory pathway, emphasizing clinical evaluation of α7nAChR agonists in postoperative patients.

© 2024 Bentham Science Publishers
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2024-11-22
2024-12-26

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/content/journals/lddd/10.2174/0115701808340483241119064321
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Mechanism of Pyroptosis in Postoperative Cognitive Dysfunction Rats and α7-nicotinic Receptor Agonist Regulating NLRP3 Inflammasome Activation
Bentham Science Publishers ; https://doi.org/10.2174/0115701808340483241119064321
/content/journals/lddd/10.2174/0115701808340483241119064321
/content/journals/lddd/10.2174/0115701808340483241119064321
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  • Article Type:     Research Article
Keywords: neuroinflammation ; Postoperative cognitive dysfunction ; α7nAChR ; interleukins ; NLRP3 inflammasome ; pyroptosis

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