Gut microbiota from mice with cerebral ischemia-reperfusion injury affects the brain in healthy mice

Abstract BACKGROUND: The aim of this study was to research the mechanism of lncRNA CEBPA-AS1 in cerebral ischemia-reperfusion injury (CIRI). METHODS: Middle cerebral artery occlusion (MCAO), MCAO/IR and OGD/R models were constructed. RNA immunoprecipitation (RIP) detected the binding of miR-340-5p to CEBPA-AS1. CEBPA-AS1 and miR-340-5p was knockdown or up-regulated. RT-PCR and western blot was processed to detect the expression of related genes and proteins. Brain tissue water content in each group was determined. Nissl staining in hippocampus of the brain and NeuN staining (green) assay was used to observe nerve damage and detect nerve cell survival, respectively. Cell viability was detected by MTT assay. Nerve cell survival was observed by immunofluorescence cytochemistry assay. LDH and MDA content were detected by kit. TUNEL was used to detect apoptosis. Luciferase reporter system was processed for verifying the binding sites. After overexpressing CEBPA-AS1 in PC-12 cells, RNA pulldown assay was performed. TTC assay was used to observe the general morphology of the brain. RESULTS: Overexpression of CEBPA-AS1 attenuated MCAO/IR-induced nerve damage. Increased CEBPA-AS1 expression reduced neuronal apoptosis in MCAO/IR model. Knockdown of CEBPA-AS1 aggravated cell damage OGD/R cell model. CEBPA-AS1 increased APPL1 expression via negatively regulating miR-340-5p, and affected APPL1/LKB1/AMPK pathway. CEBPA-AS1 attenuated OGD/R-induced cell damage by reducing miR-340-5p levels. CONCLUSIONS: LncRNA CEBPA-AS1 could alleviate cerebral ischemia-reperfusion injury by sponging miR-340-5p to regulate APPL1/LKB1/AMPK pathway.

Download Full-text

Interleukin 15 blockade protects the brain from cerebral ischemia-reperfusion injury

Brain Behavior and Immunity ◽

10.1016/j.bbi.2018.06.021 ◽

2018 ◽

Vol 73 ◽

pp. 562-570 ◽

Cited By ~ 16

Author(s):

Gilbert Aaron Lee ◽

Teng-Nan Lin ◽

Cheng-Yu Chen ◽

Shin-Yi Mau ◽

Wan-Zhen Huang ◽

...

Keyword(s):

Cerebral Ischemia ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury ◽

Interleukin 15 ◽

The Brain

Download Full-text

Effects of Thymoquinone on Small-Molecule Metabolites in a Rat Model of Cerebral Ischemia Reperfusion Injury Assessed using MALDI-MSI

Metabolites ◽

10.3390/metabo10010027 ◽

2020 ◽

Vol 10 (1) ◽

pp. 27 ◽

Cited By ~ 2

Author(s):

Fang Tian ◽

Runzhe Liu ◽

Chaoxin Fan ◽

Yi Sun ◽

Xi Huang ◽

...

Keyword(s):

Cerebral Ischemia ◽

Reperfusion Injury ◽

Small Molecule ◽

Rat Model ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Ionization Mass ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury ◽

The Brain

Thymoquinone is one of the main components present in Nigella sativa seeds and is known to have various biological functions in inflammation, oxidative stress, tumors, aging, and in lowering blood glucose levels. Few studies have focused on its neuroprotective effects and its regulation of small-molecule metabolites during cerebral ischemia reperfusion injury. In this study, transient middle cerebral occlusion (tMCAO) was used to establish the rat model of cerebral ischemia reperfusion injury. We investigated the effects of thymoquinone using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) in a model of ischemia reperfusion injury to explore the changes in small-molecule metabolites in the brain. We found that that thymoquinone significantly improved neurobehavioral scores, reduced the cerebral infarct area, alleviated brain edema, and increased the number of normal neurons following injury. MALDI-MSI revealed that thymoquinone reduced abnormal accumulations of glucose, citric acid, succinate and potassium ions. Thymoquinone also increased the amount of energy-related molecules such as ADP, AMP, GMP, and creatine, antioxidants such as glutathione, ascorbic acid, and taurine, and other metabolism-related molecules such as glutamate, glutamine, aspartate, N-acetyl-L-aspartate, and sodium ions in damaged areas of the brain following cerebral ischemia reperfusion injury. In summary, based on the neuroprotective effect of thymoquinone on cerebral ischemia reperfusion injury, this study revealed the regulation of thymoquinone on energy metabolism and small-molecule substance metabolism.

Download Full-text

Brazilein protects the brain against focal cerebral ischemia reperfusion injury correlating to inflammatory response suppression

European Journal of Pharmacology ◽

10.1016/j.ejphar.2006.11.059 ◽

2007 ◽

Vol 558 (1-3) ◽

pp. 88-95 ◽

Cited By ~ 46

Author(s):

Jia Shen ◽

Hongyin Zhang ◽

Han Lin ◽

Hui Su ◽

Dongming Xing ◽

...

Keyword(s):

Cerebral Ischemia ◽

Inflammatory Response ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Focal Cerebral Ischemia ◽

Ischemia Reperfusion ◽

Response Suppression ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury ◽

The Brain

Download Full-text

Tibetan Medicine Qishiwei Zhenzhu Pills Can Reduce Cerebral Ischemia-Reperfusion Injury by Regulating Gut Microbiota and Inhibiting Inflammation

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/2251679 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Ke Fu ◽

Dewei Zhang ◽

Yinglian Song ◽

Min Xu ◽

Ruixia Wu ◽

...

Keyword(s):

Cerebral Ischemia ◽

Inflammatory Response ◽

Gut Microbiota ◽

Cerebral Infarction ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Tibetan Medicine ◽

Cerebral Ischemia Reperfusion ◽

Cerebral Ischemia Reperfusion Injury

Cerebral ischemia is a series of harmful reactions, such as acute necrosis of tissue, inflammation, apoptosis, autophagy, and blood-brain barrier injury, due to the insufficient blood supply to the brain. Inflammatory response and gut microbiota imbalance are important concomitant factors of cerebral ischemia and may increase the severity of cerebral ischemia through the gut-brain axis. Qishiwei Zhenzhu pills (QSW) contain more than 70 kinds of medicinal materials, which have the effects of anti-cerebral infarction, anti-convulsion, anti-dementia, and so on. It is a treasure of Tibetan medicine commonly used in the treatment of cerebral ischemia in Tibetan areas. In this study, we gave rats QSW (66.68 mg/kg) once by gavage in advance and then immediately established the rat middle cerebral artery occlusion (MCAO) model. After 24 hours of treatment, the neuroprotection, intestinal pathology, and gut microbiota were examined. The results showed that QSW could significantly reduce the neurobehavioral abnormalities and cerebral infarction rate in MCAO rats. Furthermore, qPCR, western blot, and immunohistochemistry results showed that QSW could effectively inhibit IL-6, IL-1β, and other inflammatory factors so as to effectively reduce the inflammatory response of MCAO rats. Furthermore, QSW could improve intestinal integrity and reduce intestinal injury. 16S rRNA sequencing showed that QSW could significantly improve the gut microbiota disorder of MCAO rats. Specifically, at the phylum level, it can regulate the abundance of Firmicutes and Proteobacteria in the gut microbiota of rats with MCAO. At the genus level, it can adjust the abundance of Escherichia and Shigella. At the species level, it can adjust the abundance of Lactobacillus johnsonii and Lactobacillus reuteri. All in all, this study is the first to show that QSW can reduce the severity of cerebral ischemia-reperfusion injury by regulating gut microbiota and inhibiting the inflammatory response.

Download Full-text