///2014 Abstract Details
2014 Abstract Details2019-07-18T14:34:47-06:00

NLRP3 inflammasome activation contributes to the neurotoxicity of sevoflurane anesthesia in neonatal mice

Abstract Number: S-41
Abstract Type: Original Research

Hong-Mei Yuan MD1 ; HongMei Yuan MD2; XiaoFeng Shen MD3; Xian Wang MD4; ShiQin Xu MD5; Jie Yan MD6

NLRP3 inflammasome activation contributes to the neurotoxicity of sevoflurane anesthesia in neonatal mice

Hong-Mei Yuan*, Xiao-Feng Shen*, Wang Xian

Department of Anesthesiology, Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China

The authors have no potential conflicts of interest to disclose.

Background: Inhaled sevoflurane causes cell death in the developing rodent brain and neurocognitive dysfunction. However, the mechanisms by which sevoflurane leads to cognitive dysfunction remain unclear. Herein, the authors investigated whether NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation contributes to the neurotoxicity of sevoflurane anesthesia in neonatal mice.

Methods: Six-day-old C57BL/6 and NLRP3 knockout (KO) mice were exposed to 3% sevoflurane 2 h daily for 3 days. The mice were killed at the end of the anesthesia, and the brain tissues were harvested and then subjected to Western blot, immunocytochemistry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction. In another set of experiment, cognitive functions were tested by fear conditioning test and social behavior was tested by social recognition and interaction tests at postnatal day 60, respectively.

Results: In wide type neonatal mice, sevoflurane anesthesia induced cognitive impairment later in adulthood as evidenced by decreased freezing response in both contextual and cued fear conditioning. Furthermore, neonatal exposure to sevoflurane significantly increased the number of apoptotic cells and enhanced neuroinflammation in the brain immediately after anesthesia. However, NLRP3 deficient mice were protected from both learning deficits and neuroinflammation when exposure to sevoflurane anesthesia.

Conclusions: Our results provide additional evidence that NLRP3 inflammasome activation is a key mechanism critically involved in the neurotoxicity of sevoflurane anesthesia in neonatal mice.



SOAP 2014