Up-regulation of microRNA-223 inhibits brain injury and hippocampal neuron apoptosis of rats after febrile seizure through the NLRP3-Caspase-1 signaling pathway

Qiangji Decoction (QJD), a classic formula, has been widely used to treat brain aging–related neurodegenerative diseases. However, the mechanisms underlying QJD’s improvement in cognitive impairment of neurodegenerative diseases remain unclear. In this study, we employed D-galactose to establish the model of brain aging by long-term D-galactose subcutaneous injection. Next, we investigated QJD’s effect on cognitive function of the model of brain aging and the mechanisms that QJD suppressing neuroinflammation as well as improving neurodegenerative changes and hippocampal neuron apoptosis. The mice of brain aging were treated with three different dosages of QJD (12.48, 24.96, and 49.92 g/kg/d, respectively) for 4 weeks. Morris water maze was used to determine the learning and memory ability of the mice. HE staining and FJB staining were used to detect the neurodegenerative changes. Nissl staining and TUNEL staining were employed to detect the hippocampal neuron apoptosis. The contents of TNF-α, IL-1β, and IL-6 in the hippocampus were detected by using ELISA. Meanwhile, we employed immunofluorescence staining to examine the levels of GFAP and IBA1 in the hippocampus. Besides, the protein expression levels of Bcl-2, Bax, caspase-3, cleaved caspase-3, AMPKα, p-AMPKα-Thr172, SIRT1, IκBα, NF-κB p65, p-IκBα-Ser32, and p-NF-κB p65-Ser536 in the hippocampus of different groups were detected by Western blot (WB). Our findings showed that the QJD-treated groups, especially the M-QJD group, mitigated learning and memory impairments of the model of brain aging as well as the improvement of neurodegenerative changes and hippocampal neuron apoptosis. Moreover, the M-QJD markedly attenuated the neuroinflammation by regulating the AMPK/SIRT1/NF-κB signaling pathway. Taken together, QJD alleviated neurodegenerative changes and hippocampal neuron apoptosis in the model of brain aging via regulating the AMPK/SIRT1/NF-κB signaling pathway.

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Endogenous sulfur dioxide regulates hippocampal neuron apoptosis in developing epileptic rats and is associated with the PERK signaling pathway

Neuroscience Letters ◽

10.1016/j.neulet.2017.11.036 ◽

2018 ◽

Vol 665 ◽

pp. 22-28 ◽

Cited By ~ 3

Author(s):

Manman Niu ◽

Ying Han ◽

Qinrui Li ◽

Jing Zhang

Keyword(s):

Sulfur Dioxide ◽

Signaling Pathway ◽

Hippocampal Neuron ◽

Neuron Apoptosis

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Dexmedetomidine exerts a protective effect on ischemic brain injury by inhibiting the P2X7R/NLRP3/Caspase-1 signaling pathway

Brain Research Bulletin ◽

10.1016/j.brainresbull.2021.05.006 ◽

2021 ◽

Author(s):

Ke Sun ◽

Jiangang Zhang ◽

Qingcheng Yang ◽

Jinzhao Zhu ◽

Xiangdong Zhang ◽

...

Keyword(s):

Brain Injury ◽

Protective Effect ◽

Signaling Pathway ◽

Ischemic Brain Injury ◽

Ischemic Brain ◽

Caspase 1

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Correction: Fangjing decoction relieves febrile seizure-induced hippocampal neuron apoptosis in rats via regulating the Akt/mTOR pathway

Bioscience Reports ◽

10.1042/bsr-20181206_cor ◽

2019 ◽

Vol 39 (1) ◽

Keyword(s):

Febrile Seizure ◽

Hippocampal Neuron ◽

Mtor Pathway ◽

Neuron Apoptosis

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

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.658720 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zhongyu Wang ◽

Juan Li ◽

Anqi Wang ◽

Zhaoyang Wang ◽

Junmin Wang ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Water Content ◽

Signaling Pathway ◽

P38 Mapk ◽

Mapk Signaling ◽

Mapk Signaling Pathway ◽

Brain Water Content ◽

Brain Water ◽

Neuron Apoptosis

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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