Traditional Mongolian medicine Eerdun Wurile improves stroke recovery through regulation of gene expression in rat brain

Saren, Gaowa; Bao, Nirong; Da, Man; Qiburi, Qiburi; Ganbold, Tsogzolmaa; Chen, Lu; Altangerel, Altanzul; Temuqile, Temuqile; Baigude, Huricha

doi:10.1016/j.jep.2018.05.011

Cited by 27 publications

(21 citation statements)

References 47 publications

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“…The rats were weighed, and then administered an intra-peritoneal injection of 4% chloral hydrate (0.1 ml/10 g i.p.) as an anesthetic agent ( 16 , 17 ). After the anesthesia, the right common carotid artery (CCA), external carotid artery (ECA), and internal carotid artery (ICA) of rats were exposed through an incision in the middle on the neck.…”

Section: Methodsmentioning

confidence: 99%

TMEM16F Aggravates Neuronal Loss by Mediating Microglial Phagocytosis of Neurons in a Rat Experimental Cerebral Ischemia and Reperfusion Model

Zhang

et al. 2020

Front. Immunol.

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Cerebral ischemia is a severe, acute condition, normally caused by cerebrovascular disease, and results in high rates of disability, and death. Phagoptosis is a newly recognized form of cell death caused by phagocytosis of viable cells, and has been reported to contribute to neuronal loss in brain tissue after ischemic stroke. Previous data indicated that exposure of phosphatidylserine to viable neurons could induce microglial phagocytosis of such neurons. Phosphatidylserine can be reversibly exposed to viable cells as a result of a calcium-activated phospholipid scramblase named TMEM16F. TMEM16F-mediated phospholipid scrambling on platelet membranes is critical for hemostasis and thrombosis, which plays an important role in Scott syndrome and has been confirmed by much research. However, few studies have investigated the association between TMEM16F and phagocytosis in ischemic stroke. In this study, a middle-cerebral-artery occlusion/reperfusion (MCAO/R) model was used in adult male Sprague-Dawley rats in vivo, and cultured neurons were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate cerebral ischemia-reperfusion (I/R) injury in vitro. We found that the protein level of TMEM16F was significantly increased at 12 h after I-R injury both in vivo and in vitro, and reversible phosphatidylserine exposure was confirmed in neurons undergoing I/R injury in vitro. Additionally, we constructed a LV-TMEM16F-RNAi transfection system to suppress the expression of TMEM16F during and after cerebral ischemia. As a result, TMEM16F knockdown alleviated motor function injury and decreased the microglial phagocytosis of viable neurons in the penumbra through inhibiting the "eat-me" signal phosphatidylserine. Our data indicate that reducing neuronal phosphatidylserine-exposure via deficiency of TMEM16F blocks phagocytosis of neurons and rescues stressed-but-still-viable neurons in the penumbra, which may contribute to reducing infarct volume and improving functional recovering.

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Section: Methodsmentioning

confidence: 99%

TMEM16F Aggravates Neuronal Loss by Mediating Microglial Phagocytosis of Neurons in a Rat Experimental Cerebral Ischemia and Reperfusion Model

Zhang

et al. 2020

Front. Immunol.

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“…RNA-seq was applied for global gene expression profiling of the hippocampus following reperfusion with orexin-A [ 13 ]. Gaowa et al performed RNA-seq to investigate transcriptome expression in a rat stroke model treated with the traditional Mongolian medicine Eerdun Wurile [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

RNA Sequencing for Gene Expression Profiles in a Rat Model of Middle Cerebral Artery Occlusion

Duan

Gan

et al. 2018

BioMed Research International

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Gene expression regulatory mechanisms in models of middle cerebral artery occlusion (MCAO) have been assessed in some studies, but questions remain. The discovery of differentially expressed genes (DEGs) between MCAO and control rats analyzed by next-generation RNA sequencing is of particular interest. These DEGs may help guide the clinical diagnosis of stroke and facilitate selection of the optimal treatment strategy. Twenty rats were equally divided into control and MCAO groups. Three rats from each group were randomly selected for RNA sequencing analysis. Sequence reads were obtained from an Illumina HiSeq2500 platform and mapped onto the rat reference genome RN6 using Hisat2. We identified 1,007 significantly DEGs with p<0.05, including 785 upregulated (fold change [FC]>2) and 222 downregulated (FC<0.5) DEGs, in brain tissue from MCAO rats compared with that from control rats, and numerous immune response genes were identified. Gene ontology (GO) analysis revealed that the majority of the most enriched and meaningful biological process terms were mainly involved in immune response, inflammatory response, cell activation, leukocyte migration, cell adhesion, response to external stimulus, cell migration, and response to wounding. Also enriched were immune-related pathways and neural-related pathways. Similar to GO molecular function terms, the enriched terms were mainly related to cytokine receptor activity. Six DEGs were verified by quantitative real-time polymerase chain reaction (qRT-PCR). Protein-protein interaction analysis of these hits revealed that MCAO affects complement and coagulation cascades and chemokine signaling pathway. Our study identified novel biomarkers that could help further elucidate MCAO mechanisms and processes.

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“…It was discovered that EW can regulate the gene expression in the peri-ischemic center, resulting in significant upregulation of growth factors including TGFβ, Igf1, and Igf2, which may contribute to nerve tissue repair and growth. EW treatment in a rat middle cerebral artery occlusion (MCAO) model also induced significant upregulation of microglia markers, including Iba-1, CX3CR1, CD68 and CSF1R, which may have resulted from anti-inflammatory polarization of microglia upon EW treatment (Gaowa et al, 2018;Qiburi et al, 2020). We hypothesize that the active molecules in EW also protect nerve tissue through direct intervention with neurons.…”

Section: Introductionmentioning

confidence: 93%

Eerdun Wurile protects neuron and promotes neurite outgrowth through regulation of apoptotic gene expression in PC-12 cells

La¹,

Ganbold²,

Saren³

et al. 2020

J. Med. Plants Res.

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Eerdun Wurile (EW) is one of the most widely used traditional Mongolian medicines for stroke recovery. Previous studies revealed that EW regulates brain gene expression in a rat model of middle cerebral artery occlusion (MCAO). However, the fraction of active components and the specific genes regulated by such fractions have not been elucidated clearly. The study shows that the extracts of EW regulate the expression of genes involved in oxidative stress and apoptosis in rat pheochromocytoma (PC-12) cells. Hydrogen peroxide (H 2 O 2)-induced cell death was reversed by EW extracts, and reactive oxygen species (ROS) production was reduced, while superoxide dismutase (SOD) activity as well as catalase (CAT) activity increased significantly. Moreover, the expression of Bcl-2, PARP and NF-kB p65 was upregulated by EW extract, while Bax was downregulated. Similarly, caspase 9 and Jnk was remarkably downregulated by EW extracts. Significantly, EW extracts promoted the neurite outgrowth of PC-12 cells. Our data collectively suggested that EW contains active fractions that regulate the expression of genes involved in oxidative stress and cell apoptosis, which may contribute to the neural protection effect of EW.

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Traditional Mongolian medicine Eerdun Wurile improves stroke recovery through regulation of gene expression in rat brain

Cited by 27 publications

References 47 publications

TMEM16F Aggravates Neuronal Loss by Mediating Microglial Phagocytosis of Neurons in a Rat Experimental Cerebral Ischemia and Reperfusion Model

TMEM16F Aggravates Neuronal Loss by Mediating Microglial Phagocytosis of Neurons in a Rat Experimental Cerebral Ischemia and Reperfusion Model

RNA Sequencing for Gene Expression Profiles in a Rat Model of Middle Cerebral Artery Occlusion

Eerdun Wurile protects neuron and promotes neurite outgrowth through regulation of apoptotic gene expression in PC-12 cells

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