Fasudil Alleviates Postoperative Neurocognitive Disorders in Mice by Downregulating the Surface Expression of α5GABAAR in Hippocampus DOI Creative Commons

Jinpeng Dong,

Zhun Wang, Lixuan Li

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(11)

Published: Nov. 1, 2024

ABSTRACT Aim Postoperative neurocognitive disorder (PND) refers to the cognitive impairment experienced by patients after surgery. As a target of sevoflurane, kind inhalation anesthetic, balance GABAergic system can be disrupted during perioperative period. In this study, we explored promoting effect abnormal elevation α5 subtype γ‐aminobutyric acid type A (GABAA) receptors caused sevoflurane and surgical trauma on PND, as well therapeutic fasudil PND. Methods Eight‐week‐old mice were pretreated with fasudil, 10 days, sevoflurane‐induced femoral fracture surgery was performed establish an animal model The Morris water maze fear conditioning tests used evaluate PND induced model. Biochemical electrophysiological analyses conducted assess protective system. Results Following artificial fracture, hippocampus‐dependent memory damaged in these mice. Fasudil pretreatment, however, ameliorated function Mechanistically, found restore increased hippocampus expression α5GABAARs addition, pretreatment inhibited enhancement calcium ion concentration phosphorylation Camk2, activation Radixin pathway which led ERM family hippocampal CA1 region Conclusion Preadministration improved postoperative inhibiting Camk2 pathways finally downregulating surface α5GABAAR neurons.

Language: Английский

Fasudil Alleviates Postoperative Neurocognitive Disorders in Mice by Downregulating the Surface Expression of α5GABAAR in Hippocampus DOI Creative Commons

Jinpeng Dong,

Zhun Wang, Lixuan Li

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(11)

Published: Nov. 1, 2024

ABSTRACT Aim Postoperative neurocognitive disorder (PND) refers to the cognitive impairment experienced by patients after surgery. As a target of sevoflurane, kind inhalation anesthetic, balance GABAergic system can be disrupted during perioperative period. In this study, we explored promoting effect abnormal elevation α5 subtype γ‐aminobutyric acid type A (GABAA) receptors caused sevoflurane and surgical trauma on PND, as well therapeutic fasudil PND. Methods Eight‐week‐old mice were pretreated with fasudil, 10 days, sevoflurane‐induced femoral fracture surgery was performed establish an animal model The Morris water maze fear conditioning tests used evaluate PND induced model. Biochemical electrophysiological analyses conducted assess protective system. Results Following artificial fracture, hippocampus‐dependent memory damaged in these mice. Fasudil pretreatment, however, ameliorated function Mechanistically, found restore increased hippocampus expression α5GABAARs addition, pretreatment inhibited enhancement calcium ion concentration phosphorylation Camk2, activation Radixin pathway which led ERM family hippocampal CA1 region Conclusion Preadministration improved postoperative inhibiting Camk2 pathways finally downregulating surface α5GABAAR neurons.

Language: Английский

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