JNK inhibition alleviates delayed neurocognitive recovery after surgery by limiting microglia pyroptosis

He, Jun; Liu, Taotao; Li, Yue; Mi, Xinning; Han, Dengyang; Yang, Ning; Chen, Lei; Li, Yitong; Hong, Jingshu; Kuang, Chongshen; Yuan, Yi; Cao, Yanyan; Han, Yongzheng; Shi, Chengmei; Li, Zhengqian; Guo, Xiangyang

doi:10.1016/j.intimp.2021.107962

Cited by 22 publications

(15 citation statements)

References 56 publications

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“…In our study, the dNCR model of aged mice was established to investigate the protective effect of MSC-Exo. Firstly, we found that an exploratory laparotomy was performed using aseptic procedures caused cognitive dysfunction in aged mice, which is in consistent with previous studies [ 39 ]. And MWM tests showed that the mice in the dNCR+MSCs-Exo group spent less time to find the platform and more time in the target quadrant than that of the dNCR group.…”

Section: Discussionsupporting

confidence: 92%

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Mesenchymal Stem Cell-Derived Exosomes Ameliorate Delayed Neurocognitive Recovery in Aged Mice by Inhibiting Hippocampus Ferroptosis via Activating SIRT1/Nrf2/HO-1 Signaling Pathway

Liu

Huang

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Delayed neurocognitive recovery (dNCR) is a prevalent perioperative neurological complication in older patients and has common characteristics such as acute cognitive dysfunction, impaired memory, and inattention. Mesenchymal stem cell-derived exosomes (MSCs-Exo) are enclosed by a lipid bilayer contain proteins, DNA, miRNA, and other components, which are important mediators of intercellular communication. It has been reported that exosomes could play an important role in the treatment of neurodegenerative diseases, nerve injury, and other neurological diseases. In this study, we examined the effects of MSCs-Exo on dNCR aged mice after exploratory laparotomy and evaluated their potential regulatory mechanisms. We found that MSCs-Exo treatment ameliorated cognitive impairment in dNCR aged mice. MSCs-Exo inhibit hippocampus ferroptosis and increase the expression of silent information regulator 1 (SIRT1), factor nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in dNCR aged mice. Interestingly, the above effects of MSCs-Exo on dNCR aged mice were abolished by SIRT1 selective inhibitor EX-527. In conclusion, these findings indicated that MSCs-Exo can ameliorate cognitive impairment by inhibiting hippocampus ferroptosis in dNCR aged mice via activating SIRT1/Nrf2/HO-1 signaling pathway, providing a potential avenue for the treatment of dNCR.

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Section: Discussionsupporting

confidence: 92%

“…To establish the model of dNCR, an exploratory laparotomy was performed using aseptic procedures as previously described [ 39 ]. Briefly, the mice were deeply anesthetized with 2.5% isoflurane; their abdomen regions were shaved and sterilized with iodophor and ethanol.…”

Section: Methodsmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes Ameliorate Delayed Neurocognitive Recovery in Aged Mice by Inhibiting Hippocampus Ferroptosis via Activating SIRT1/Nrf2/HO-1 Signaling Pathway

Liu

Huang

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Mice were randomized into 4 groups: (1) control group (CON), mice received no intervention but anesthesia (described as follows); (2) anesthesia/surgery group (A/S), mice received a laparotomy under sevo urane anesthesia (induced with 5% sevo urane for 2-3 min, and maintained with 2.5-3% sevo urane for 30 min in 40% oxygen). The laparotomy was performed in accordance with previous studies (21,42,43). Brie y, after disinfection, a 1.5 cm midline incision was made 0.5 cm below the xiphoid and abdominal organs were explored.…”

Section: Anesthesia/ Surgerymentioning

confidence: 99%

“…Morris water maze is a common behavior to test hippocampus-dependent spatial navigation and reference memory for rodents (44), we conducted this experiment according to previous research with minor modi cations (43). A circular tank (110 cm in diameter and 60 cm in height) was lled with 35 cm of water tinted white using titanium dioxide and maintained at 24 ± 1°C, dividing into 4 quadrants.…”

Section: Behavioral Testmentioning

confidence: 99%

WITHDRAWN: Low-intensity pulsed ultrasound attenuates postoperative neurocognitive impairment and salvages hippocampal synaptogenesis in aged mice

Wang

Liu

Chang

et al. 2022

Preprint

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Background Postoperative neurocognitive impairment is an urgent problem with global aging accelerating. The prevention and treatment of postoperative neurocognitive impairment have been widely investigated but lack effective strategies. Low-intensity pulsed ultrasound (LIPUS), a non-invasive tool, has shown an effect on neuroprotection, but whether it could attenuate the postoperative neurocognitive impairment and the underlying mechanism remains unknow. Methods An experimental set-up for LIPUS stimulation of the hippocampus was well established. HE staining was used to determine the morphology of hippocampus after LIPUS application. A laparotomy model in aged mice was applied, and Morris water maze was used to assess cognitive function. RT-qPCR and western blotting were used to detect levels of inflammatory cytokines, synapse associated protein in the hippocampus, respectively. Immunofluorescent staining was also used to determine the neural activation and Piezo1 expression. Results After the anesthesia/surgery, the hippocampus of aged mice showed increased levels of inflammation and decreased synaptogenesis, while LIPUS intervention improved cognitive impairment, reduced hippocampal neuroinflammation, and improved synaptogenesis. We further found that LIPUS might improve synaptogenesis through the Piezo1-mediated calpain1/extracellular regulated protein kinases (Erk) pathway. Conclusion Our results suggested that LIPUS could be used as an effective physical intervention to improve postoperative cognitive dysfunction in the aged population.

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“…Celastrol may alleviate spinal cord inflammation in rats in the acute phase by inhibiting microglia pyroptosis ( Dai et al, 2019 ). c-Jun N-terminal kinases also reduce the time to neurocognitive recovery after surgery by inhibiting microglia pyroptosis ( He et al, 2021 ). In addition, lncRNA F630028O10Rik, lncRNA H19, and CD73 are involved in the progression of neurological diseases by promoting microglia pyroptosis ( Wan et al, 2020 ; Xu et al, 2020a , 2021 ).…”

Section: Microglia Polarization and Pathogenic Mechanisms In The Cent...mentioning

confidence: 99%

LncRNA, an Emerging Approach for Neurological Diseases Treatment by Regulating Microglia Polarization

et al. 2022

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Neurological disorders cause untold human disability and death each year. For most neurological disorders, the efficacy of their primary treatment strategies remains suboptimal. Microglia are associated with the development and progression of multiple neurological disorders. Targeting the regulation of microglia polarization has emerged as an important therapeutic strategy for neurological disorders. Their pro-inflammatory (M1)/anti-inflammatory (M2) phenotype microglia are closely associated with neuronal apoptosis, synaptic plasticity, blood-brain barrier integrity, resistance to iron death, and astrocyte regulation. LncRNA, a recently extensively studied non-coding transcript of over 200 nucleotides, has shown great value to intervene in microglia polarization. It can often participate in gene regulation of microglia by directly regulating transcription or sponging downstream miRNAs, for example. Through proper regulation, microglia can exert neuroprotective effects, reduce neurological damage and improve the prognosis of many neurological diseases. This paper reviews the progress of research linking lncRNAs to microglia polarization and neurological diseases.

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JNK inhibition alleviates delayed neurocognitive recovery after surgery by limiting microglia pyroptosis

Cited by 22 publications

References 56 publications

Mesenchymal Stem Cell-Derived Exosomes Ameliorate Delayed Neurocognitive Recovery in Aged Mice by Inhibiting Hippocampus Ferroptosis via Activating SIRT1/Nrf2/HO-1 Signaling Pathway

Mesenchymal Stem Cell-Derived Exosomes Ameliorate Delayed Neurocognitive Recovery in Aged Mice by Inhibiting Hippocampus Ferroptosis via Activating SIRT1/Nrf2/HO-1 Signaling Pathway

WITHDRAWN: Low-intensity pulsed ultrasound attenuates postoperative neurocognitive impairment and salvages hippocampal synaptogenesis in aged mice

LncRNA, an Emerging Approach for Neurological Diseases Treatment by Regulating Microglia Polarization

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