Dysfunction of inflammation-resolving pathways is associated with postoperative cognitive decline in elderly mice

Wang, Gongming; Li, Guodong; Liu, Jie; Sun, Panpan; Xu, Lichi; Li, Jingjing; Guo, Yanjing; Zhang, Mengyuan

doi:10.1016/j.bbr.2020.112538

Cited by 21 publications

(12 citation statements)

References 36 publications

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“…Studies have showed that sevoflurane could cause downregulation of neurotrophic factors in developing brain (Tang et al, 2020;Zhao et al, 2021). As is mentioned above, like the developing brain, the aged brain is fragile brain which is more susceptible to external harmful factors compared with adult brain (Wang Z. et al, 2018;Xu et al, 2018;Yang and Yuan, 2018;Gong et al, 2020). Therefore, sevoflurane induces AHN inhibition and BDNF/NT-3 downregulation in aged mice while it has no effect on AHN and BDNF/NT-3 expression in adult mice.…”

Section: Discussionmentioning

confidence: 98%

“…Developing brain and aged brain are fragile brains which are more susceptible to external harmful stimuli than adult brain (Y. Zhao et al, 2016;Gong et al, 2020;Yu et al, 2020). The mechanisms are related to neurogenesis, autophagy, Tau protein deposition, neuroinflammation, neuronal excitability, etc.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms are related to neurogenesis, autophagy, Tau protein deposition, neuroinflammation, neuronal excitability, etc. (Fang et al, 2012;Zhang et al, 2013;Zhao et al, 2016;Xu et al, 2018;Wang et al, 2019;Gong et al, 2020;Yu et al, 2020). The effect of sevoflurane on cognition is also related to the dose.…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of Adult Hippocampal Neurogenesis Plays a Role in Sevoflurane-Induced Cognitive Impairment in Aged Mice Through Brain-Derived Neurotrophic Factor/Tyrosine Receptor Kinase B and Neurotrophin-3/Tropomyosin Receptor Kinase C Pathways

Guo

Wang

et al. 2022

Front. Aging Neurosci.

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Sevoflurane anesthesia induces cognitive impairment, which may lead to perioperative neurocognitive disorders (PND). However, the factors and molecular mechanism underlying this impairment remains unclear. Adult hippocampal neurogenesis (AHN) in the subgranular zone of the hippocampus has been implicated in cognitive processes. Nonetheless, the direct role of AHN in sevoflurane-induced cognitive impairment has never been demonstrated. In this study, we explored the age and the concentration factors and the role of AHN inhibition in sevoflurane-induced cognitive impairment in sevoflurane inhalation model mice. We found that 3% sevoflurane exposure induced significant cognitive impairment and inhibition of AHN in aged mice but not adult mice. Expression of BDNF/TrkB and NT-3/TrkC was also decreased by 3% sevoflurane exposure in aged mice. Hippocampal brain-derived neurotrophic factor (BDNF) or Neurotrophin-3 (NT-3) microinjection could partially improve the sevoflurane-induced cognitive impairment and AHN inhibition, respectively. These results demonstrate that the cognitive impairment caused by sevoflurane inhalation is related to patient age and sevoflurane concentration. In conclusion, the molecular mechanism of cognitive impairment in the elderly is related to the inhibition of AHN through the BDNF/TrkB and NT-3/TrkC pathways. Thus, sevoflurane inhalation anesthesia may be safe for adult patients, but caution should be exercised when administering it to the elderly.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Inhibition of Adult Hippocampal Neurogenesis Plays a Role in Sevoflurane-Induced Cognitive Impairment in Aged Mice Through Brain-Derived Neurotrophic Factor/Tyrosine Receptor Kinase B and Neurotrophin-3/Tropomyosin Receptor Kinase C Pathways

Guo

Wang

et al. 2022

Front. Aging Neurosci.

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“…Preventive interventions discussed above can also be used for the treatment of POCD. Several preclinical and clinical studies suggested that targeting postoperative neuro-inflammation [87][88][89][90][91] may be a potential way to treat POCD. There are some medications used in the clinical trials attempted to block the process of neuroinflammation.…”

Section: Treatment Of Pocdmentioning

confidence: 99%

Recent advances and perspectives of postoperative neurological disorders in the elderly surgical patients

et al. 2021

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“…The occurrence of POCD is closely related to the anesthesia used during the operation [3]. POCD was first proposed by Bedford in 1955 and was defined as "the brain damage caused by anesthesia in the elderly" [4]. The precise pathogenesis of POCD is still unknown today.…”

Section: Introductionmentioning

confidence: 99%

Up-regulation of miR-20a ameliorates sevoflurane anesthesia-induced cognitive impairment in rats by targeting EphA4

Qian¹,

Chen²,

Dong³

et al. 2022

Trop. J. Pharm Res

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Purpose: To evaluate the role of miR-20a in sevoflurane (SEV)-induced cognitive impairment in rats and to elucidate the mechanism of action. Methods: A SEV-induced cognitive impairment rat model was developed. The Morris water maze test and fear assay were carried out to assess impaired learning and memory. A cellular SEV-impaired model was developed and the miR-20a level was measured in the animal and cellular models. TUNEL staining and immunoblot assay were performed to determine the SEV effect on apoptosis. Bioinformatic analysis and luciferase assay were conducted to identify the target of miR-20a action. A rescue assay involving miR-20a overexpression in cellular and animal models was developed and used to evaluate function of miR-20a in cognitive defects. Results: The rats showed significant cognitive impairment upon SEV treatment, which inhibited the expression of miR-20a and promoted neuronal apoptosis. Further findings identified EphA4 as a target of miR-20a, which regulates its expression. Overexpression of miR-20a in rats effectively reduced cognitive dysfunction and apoptosis of hippocampus somatic cells caused by SEV treatment. Conclusion: Evidently, miR-20a ameliorates SEV anesthesia-induced cognitive impairment in rats and thus has the potential to serve as a therapeutic target for the treatment of post-operative cognitive dysfunction.

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Dysfunction of inflammation-resolving pathways is associated with postoperative cognitive decline in elderly mice

Cited by 21 publications

References 36 publications

Inhibition of Adult Hippocampal Neurogenesis Plays a Role in Sevoflurane-Induced Cognitive Impairment in Aged Mice Through Brain-Derived Neurotrophic Factor/Tyrosine Receptor Kinase B and Neurotrophin-3/Tropomyosin Receptor Kinase C Pathways

Inhibition of Adult Hippocampal Neurogenesis Plays a Role in Sevoflurane-Induced Cognitive Impairment in Aged Mice Through Brain-Derived Neurotrophic Factor/Tyrosine Receptor Kinase B and Neurotrophin-3/Tropomyosin Receptor Kinase C Pathways

Recent advances and perspectives of postoperative neurological disorders in the elderly surgical patients

Up-regulation of miR-20a ameliorates sevoflurane anesthesia-induced cognitive impairment in rats by targeting EphA4

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