Compound Porcine Cerebroside and Ganglioside Injection (CPCGI) Attenuates Sevoflurane-Induced Nerve Cell Injury by Regulating the Phosphorylation of p38 MAP Kinase (p38MAPK)/Nuclear Factor kappa B (NF-κB) Pathway

Song, Hualin; Xun, Shining; He, Huiwen; Duan, Chongzhen; Li, Qiang

doi:10.12659/msm.919600

Cited by 3 publications

(1 citation statement)

References 30 publications

(38 reference statements)

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“…Besides, up-regulation of p38-MAPK was previously implicated in preventing cerebrovascular autoregulation impairment following TBI ( Armstead et al, 2013 ). It is noteworthy that, p-p38 has been observed to be up-regulated in a time-dependent manner following treatment with 3% sevoflurane in hippocampal neurons, which are damaged by sevoflurane ( Song et al, 2020 ). Together, these findings and data indicate that appropriate concentration and period of sevoflurane treatment warrants further exploration in the future for clinical application.…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane Inhibits Traumatic Brain Injury-Induced Neuron Apoptosis via EZH2-Downregulated KLF4/p38 Axis

Wang

et al. 2021

Front. Cell Dev. Biol.

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Traumatic brain injury (TBI) is characterized by physical damage to the brain tissues, ensuing transitory or permanent neurological dysfunction featured with neuronal loss and subsequent brain damage. Sevoflurane, a widely used halogenated anesthetic in clinical settings, has been reported to alleviate neuron apoptosis in TBI. Nevertheless, the underlying mechanism behind this alleviation remains unknown, and thus was the focus of the current study. First, Feeney models were established to induce TBI in rats. Subsequently, evaluation of the modified neurological severity scores, measurement of brain water content, Nissl staining, and TUNEL assay were employed to investigate the neuroprotective effects of sevoflurane. Immunofluorescence and Western blot analysis were further applied to detect the expression patterns of apoptosis-related proteins as well as the activation of the p38-mitogen-activated protein kinase (MAPK) signaling pathway within the lesioned cortex. Additionally, a stretch injury model comprising cultured neurons was established, followed by neuron-specific enolase staining and Sholl analysis. Mechanistic analyses were performed using dual-luciferase reporter gene and chromatin immunoprecipitation assays. The results demonstrated sevoflurane treatment brought about a decrease blood-brain barrier (BBB) permeability, brain water content, brain injury and neuron apoptosis, to improve neurological function. The neuroprotective action of sevoflurane could be attenuated by inactivation of the p38-MAPK signaling pathway. Mechanistically, sevoflurane exerted an inhibitory effect on neuron apoptosis by up-regulating enhancer of zeste homolog 2 (EZH2), which targeted Krüppel-like factor 4 (KLF4) and inhibited KLF4 transcription. Collectively, our findings indicate that sevoflurane suppresses neuron apoptosis induced by TBI through activation of the p38-MAPK signaling pathway via the EZH2/KLF4 axis, providing a novel mechanistic explanation for neuroprotection of sevoflurane in TBI.

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Section: Discussionmentioning

confidence: 99%

Sevoflurane Inhibits Traumatic Brain Injury-Induced Neuron Apoptosis via EZH2-Downregulated KLF4/p38 Axis

Wang

et al. 2021

Front. Cell Dev. Biol.

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Functions of glycosphingolipids in the central nervous system

Guo

2024

Glycosphingolipids in the Central Nervous System

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Compound porcine cerebroside and ganglioside injections improved anxiety and cognitive dysfunction through the NF-κB pathway in cerebral ischemia-reperfusion injury

Tian

et al. 2023

Preprint

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Background Cerebral ischemia-reperfusion injury (CIRI) can cause hippocampal inflammation and apoptosis, resulting in anxiety and cognitive dysfunction. Compound porcine cerebroside and ganglioside injections (CPCGI) are used to treat encephalopathy, but its therapeutic effects and mechanism require further exploration. Methods We screened key genes associated with the ischemic stroke (IS) and predicted their binding sites with CPCGI. We subsequently injected CPCGI into a middle cerebral artery occlusion (MCAO) rat model. 2,3,5-triphenyl tetrazolium chloride (TTC) staining and behavioral testing were performed. Hippocampal neuronal apoptosis was assessed by immunofluorescence. IL-1β, TNF-α, and NF-κB pathway were detected by Western blotting. Oxygen-glucose deprivation/reoxygenation (OGD/R)-HT-22 cells were treated CPCGI for 72 h. Cell viability and NF-κB were also evaluated. Results H2AC20, RPL3, RPL13A, RPL9, RPS23, and RPLP0 were identified as key IS genes. CPCGI was confirmed to interact with these proteins via molecular docking. Functional enrichment reflected the critical role of the NF-κB pathway in CIRI. Infarct volume and behavioral impairments in MCAO rats, especially anxiety and cognitive dysfunction, were improved by CPCGI in a dose-dependent manner. Immunofluorescence confirmed that hippocampal neuronal apoptosis was rescued by the CPCGI. Western blotting revealed that inflammation and NF-κB phosphorylation were inhibited. In vitro experiments showed that CPCGI increased the survival of OGD/R-HT-22 cells and inhibited phosphorylation of the NF-κB signaling pathway. Conclusion CPCGI can alleviate anxiety and cognitive dysfunction in CIRI and thus improve psychoneurological symptoms in patients with IS. We confirmed that CPCGI alleviate inflammation and apoptosis in the hippocampus by inhibiting the NF-κB signaling pathway.

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Compound Porcine Cerebroside and Ganglioside Injection (CPCGI) Attenuates Sevoflurane-Induced Nerve Cell Injury by Regulating the Phosphorylation of p38 MAP Kinase (p38MAPK)/Nuclear Factor kappa B (NF-κB) Pathway

Cited by 3 publications

References 30 publications

Sevoflurane Inhibits Traumatic Brain Injury-Induced Neuron Apoptosis via EZH2-Downregulated KLF4/p38 Axis

Sevoflurane Inhibits Traumatic Brain Injury-Induced Neuron Apoptosis via EZH2-Downregulated KLF4/p38 Axis

Functions of glycosphingolipids in the central nervous system

Compound porcine cerebroside and ganglioside injections improved anxiety and cognitive dysfunction through the NF-κB pathway in cerebral ischemia-reperfusion injury

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