Perioperative Complication
Role of NMDA receptors in sevoflurane anesthesia-caused necroptosis in hippocampal neurons of aged mice
Yu Jiaxu, Zhang Qi, Yin Chunping, Li Yanan, Li Wi, Zhu Lian, Hou Zhiyong, Wang Qiujun
Published 2022-01-20
Cite as Chin J Anesthesiol, 2022, 42(1): 55-59. DOI: 10.3760/cma.j.cn131073.20211106.00111
Abstract
ObjectiveTo evaluate the role of N-methyl-D-aspartate receptors (NMDA receptors) in sevoflurane anesthesia-caused necroptosis in hippocampal neurons of aged mice.
MethodsNinety clean-grade healthy male C57BL/6 mice, aged 18 months, weighing 27-30 g, were divided into 3 groups (n=30 each) using a random number table method: control group (group C), sevoflurane anesthesia group (group S) and sevoflurane anesthesia plus NMDA receptor antagonist memantine hydrochloride group (group S+ M). Mice inhaled 3% sevoflurane for 2 h for 3 consecutive days in S group and S+ M group, and memantine hydrochloride 20 mg/kg was intraperitoneally injected at 1 h before each inhalation of sevoflurane in S+ M group.Mice only inhaled pure oxygen for 2 h in group C. Ten mice of each group were selected on 1 day before anesthesia and 3 and 7 days after anesthesia to perform Morris water maze test.The mice were sacrificed immediately after Morris water maze test, and hippocampus was removed for microscopic examination of pathological changes (with a light microscope) and for determination of the necroptosis rate of neurons and cytoplasmic free calcium concentration([Ca2+ ]i)(by flow cytometry), and expression of NMDA receptor subtypes GluN2A, GluN2B and receptor-interacting protein kinase 1 (RIP1) (by Western blot).
ResultsCompared with group C, the escape latency was significantly prolonged, and the frequency of crossing the original platform was decreased, and the [Ca2+ ]i and neuronal necroptosis rate in the hippocampus were increased at each time point after anesthesia, and the expression of GluN2A, GluN2B and RIP1 was up-regulated(P<0.05), and the pathologic changes were accentuated in S group and S+ M group.Compared with group S, the escape latency was significantly shortened, and the frequency of crossing the original platform was increased, and the [Ca2+ ]i and neuronal necroptosis rate in the hippocampus were decreased at each time point after anesthesia, and the expression of GluN2A, GluN2B and RIP1 was down-regulated (P<0.05), and the pathologic changes were attenuated in group S+ M.
ConclusionsNMDA receptors are involved in the process of cognitive dysfunction induced by sevoflurane anesthesia in aged mice, and the mechanism may be related to the promotion of necrptosis in hippocampal neurons.
Key words:
Receptors, N-methyl-D-aspartate; Anesthetics, inhalation; Aged; Hippocamus; Neurons; Necrosis
Contributor Information
Yu Jiaxu
Department of Anesthesiology, Third Hospital of Hebei Medical University, Shijiazhuang 050051, China
Zhang Qi
Department of Anesthesiology, Hebei Children′s Hospital, Shijiazhuang 050030, China
Yin Chunping
Department of Anesthesiology, Third Hospital of Hebei Medical University, Shijiazhuang 050051, China
Li Yanan
Department of Anesthesiology, Third Hospital of Hebei Medical University, Shijiazhuang 050051, China
Li Wi
Department of Anesthesiology, Third Hospital of Hebei Medical University, Shijiazhuang 050051, China
Zhu Lian
Center of Emergency and Trauma, Third Hospital of Hebei Medical University, Shijiazhuang 050051, China
Hou Zhiyong
Center of Emergency and Trauma, Third Hospital of Hebei Medical University, Shijiazhuang 050051, China
Wang Qiujun
Department of Anesthesiology, Third Hospital of Hebei Medical University, Shijiazhuang 050051, China
