ATPase Inhibitory Factor 1 Is Critical for Regulating Sevoﬂurane-Induced Microglial Inﬂammatory Responses and Caspase-3 Activation

Frontiers in Cellular Neuroscience, 2021 · DOI: 10.3389/fncel.2021.770666 · Published: December 15, 2021

Simple Explanation

Postoperative delirium (POD) is a complication after surgery with general anesthesia, and the neurotoxicity of general anesthetics is a high-risk factor. This study found that the general anesthetic sevoﬂurane increased inflammatory factors and activated caspase-3 in microglia. The study reveals that ATPIF1, an important protein regulating ATP synthesis, mediates sevoﬂurane-induced neurotoxicity in microglia. ATP supplementation may be a potential clinical treatment to alleviate sevoﬂurane-induced POD. Animal experiments indicated that intraperitoneal injection of ATP significantly alleviated sevoﬂurane anesthesia-induced POD-related anxiety behavior and memory damage in mice.

Study Duration

Not specified

Participants

C57BL/6 mice

Evidence Level

Level: Not specified, Type: Original Research

Key Findings

1
Sevoﬂurane upregulates the expression of ATPIF1 to induce inflammation and caspase-3 activation.
2
Extracellular supplementation with ATP ameliorates the inflammation and caspase-3 activation induced by ATPIF1 overexpression.
3
ATP supplementation significantly alleviates the anxiety and memory damage induced by sevoﬂurane anesthesia.

Research Summary

This study confirms that a clinical concentration of general anesthetic sevoﬂurane increased the expression of inflammatory factors in microglia and activated the caspase-3 by upregulating ATPIF1 expression in microglia. Animal experiments further indicated that intraperitoneal injection of ATP significantly alleviated the anxiety and memory damage induced by sevoﬂurane anesthesia in a POD mouse model, which provides a potential convenient strategy for the future clinical treatment of POD. The present study revealed that ATPIF1 acts as a negative regulator to induce the neurotoxicity of sevoﬂurane on microglia, further improving POD-associated behavioral responses.

Practical Implications

Potential Clinical Treatment

ATP supplementation may be a potential clinical treatment to alleviate sevoﬂurane-induced POD.

Therapeutic Target

ATPIF1 can be considered an important mediator that contributes to the inflammatory response and apoptosis of microglia caused by sevoﬂurane.

POD Prevention Strategy

Therapeutic approaches designed to appropriately supplement ATP might be attractive POD prevention and treatment strategies.

Study Limitations

1
The mechanism by which sevoﬂurane regulates ATP production remains largely unclear.
2
Understanding of whether general anesthesia affects ATPIF1 to regulate downstream signaling pathways leading to POD pathogenesis is rather limited.
3
Whether there is a particular molecule that can mediate both sevoﬂurane-induced microglial activation and apoptotic effects is still unclear.

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