Astroglial N‐myc downstream‐regulated gene 2 protects the brain from cerebral edema induced by stroke

Guo, Huiling; Yin, Anqi; Ma, Yulong; Fan, Ze; Tao, Liang; Wen-hong, Tang; Ma, Yue; Hou, Wugang; Cai, Guohong; Zhuo, Lixia; Zhang, Jian; Li, Yan; Xiong, Lize

doi:10.1002/glia.23888

Cited by 15 publications

(9 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has also been reported that relatively small changes in the brain water content can reflect large changes in the absolute water content of the brain and brain swelling ( Keep et al, 2012 ). Thus, cerebral edema caused by hyponatremia can result in massive cerebral swelling, subsequently increased intracranial pressure, rapid neurological deterioration, and increased morbidity and mortality following ischemic stroke ( Chen et al, 2021 ; Guo et al, 2021 ). Our study found that patients with hyponatremia had higher NIHSS scores at admission than those without hyponatremia.…”

Section: Discussionmentioning

confidence: 99%

Hyponatremia Is Associated With Post-thrombolysis Hemorrhagic Transformation and Poor Clinical Outcome in Ischemic Stroke Patients

Guo

et al. 2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

ObjectiveHyponatremia is the most common electrolyte disorder encountered in patients with neurological conditions, such as stroke. Studies have shown that it is associated with worse clinical outcomes and increased mortality in acute ischemic stroke (AIS). However, the role of hyponatremia has not been elucidated in patients with AIS who received intravenous thrombolysis (IVT) therapy. Therefore, this study aimed to investigate the effect of serum sodium levels on the clinical outcome and hemorrhagic transformation (HT) in patients with AIS who received thrombolytic therapy.MethodsPatients diagnosed with AIS who received IVT therapy between May 2015 and December 2020 were included in this study. All patients were screened for serum sodium levels immediately after hospital admission, before IVT therapy. The occurrence of HT was evaluated using computed tomography (CT) 24 ± 2 h after thrombolysis. Then, 3-month clinical outcomes were obtained by telephone calls or outpatient visits, and poor 3-month clinical outcomes were defined as modified Rankin Scale scores ≥3. The effects of serum sodium levels on the clinical outcome and HT were assessed using the multivariate logistic regression analysis.ResultsOf the 963 included patients, 82 (8.5%) had hyponatremia, 157 (16.3%) developed HT, and 333 (34.6%) had poor 3-month outcomes. Of the 82 patients with hyponatremia, 21 (25.6%) developed HT, and 39 (47.6%) had poor 3-month outcomes. Patients with hyponatremia had a higher incidence of post-thrombolysis HT (25.6 vs. 15.4%, p = 0.017) and worse clinical outcome (47.6 vs. 33.4%, p = 0.01) than those with normal serum sodium levels. Patients had significantly lower serum sodium levels in those with HT [138.4 (136.4–140.3, IQR) vs. 139.0 (137.2–140.7, IQR) mmol/L, p = 0.019] and poor 3 month outcome [139.0 (137.2–140.7) vs. 138.4 (136.7–140.3) mmol/L, p = 0.005] than those without. After adjusting for major covariates, the multivariate logistic regression analysis revealed that lower serum sodium levels were independently associated with an increased risk of HT [odds ratio (OR) = 1.804; 95% CI: 1.048–3.105] and poor 3-month outcome (OR = 1.647; 95% CI: 1.012–2.679).ConclusionLower serum sodium level was an independent risk factor for post-thrombolysis HT and poor clinical outcome in patients with AIS who received thrombolytic therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Hyponatremia Is Associated With Post-thrombolysis Hemorrhagic Transformation and Poor Clinical Outcome in Ischemic Stroke Patients

Guo

et al. 2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…We previously rst found that Ndrg2-knockout male mice had much larger cerebral infarction volumes compared with wild-type male mice [11]. We further found that Ndrg2 knockouts male mice aggravates injury due to brain edema following cerebral ischemia [12]. These results demonstrate that Ndrg2 could be a potential target for the neuroprotection against cerebral ischemia in male mice.…”

Section: Introductionmentioning

confidence: 63%

N-Myc Downstream-Regulated Gene 2 (Ndrg2): A Critical Mediator of Estrogen-Induced Neuroprotection Against Cerebral Ischemic Injury

Zhang

Liu

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Growing evidence indicates that estrogen plays a pivotal role in neuroprotection against cerebral ischemia, but the molecular mechanism of this protection is still elusive. N-myc downstream‐regulated gene 2 (Ndrg2), an estrogen-targeted gene, has been shown to exert neuroprotective effects against cerebral ischemia in male mice. However, the role of Ndrg2 in the neuroprotective effect of estrogen remains unknown. In this study, we first detected NDRG2 expression levels in the cortex and striatum in both female and male mice with western blot analyses. We then detected cerebral ischemic injury by constructing middle cerebral artery occlusion and reperfusion (MCAO-R) models in Ndrg2 knockout or conditional knockdown female mice. We further implemented estrogen, ERα or ERβ agonist replacement in the ovariectomized (OVX) Ndrg2 knockouts or conditional knockdowns female mice, then tested for NDRG2 expression, glial fibrillary acidic protein (GFAP) expression, and extent of cerebral ischemic injury. We found that NDRG2 expression was significantly higher in female than in male mice in both the cortex and striatum. Ndrg2 knockouts and conditional knockdowns showed significantly aggravated cerebral ischemic injury in female mice. Estrogen and ERβ replacement treatment (DPN) led to NDRG2 upregulation in both the cortex and striatum of OVX mice. Estrogen and DPN also led to GFAP upregulation in OVX mice. However, the effect of estrogen and DPN in activating astrocytes was lost in Ndrg2 knockouts OVX mice and primary cultured astrocytes, but partially retained in conditional knockdowns OVX mice. Most importantly, we found that the neuroprotective effects of E2 and DPN against cerebral ischemic injury were lost in Ndrg2 knockouts OVX mice but partially retained in conditional knockdowns OVX mice. These findings demonstrate that estrogen alleviated cerebral ischemic injury via ERβ upregulation of Ndrg2, which could activate astrocytes, indicating that Ndrg2 is a critical mediator of E2-induced neuroprotection against cerebral ischemic injury.

show abstract

“…Ma et al have found that MYC was involved in ischemia–hypoxia-induced astrocyte apoptosis 50 . Some studies have found that MYC downstream-regulated genes can protect the integrity of blood–brain barrier and cerebral edema following cerebral ischemia 51,52 . Ewida et al reported that HIF1A can improve the prognosis of stroke by activating angiogenesis 53,54 .…”

Section: Discussionmentioning

confidence: 99%

Uncovering the Mechanism of Chuanhong Stroke Capsule in the Treatment of Stroke Based on Network Pharmacology and Molecular Docking Technology

Wang

Zhao

Kan

et al. 2022

Natural Product Communications

View full text Add to dashboard Cite

Background and Objective: Chuanhong Stroke Capsule (CHSC) has good clinical efficacy in the treatment of cerebral ischemic stroke (CIS) patients. This study aimed to investigate the pharmacological mechanisms of CHSC in treating CIS using bioinformatics. Methods: The active compounds of CHSC were screened by searching Traditional Chinese Medicine System Pharmacological Database and Analysis Platform (TCMSP), Swiss absorption, distribution, metabolism, and excretion (ADME), PubMed, and China National Knowledge Infrastructure (CNKI) databases. Besides, the potential targets of active compounds were obtained through TCMSP and Swiss Target Prediction databases. CIS targets were obtained from GeneCards, Online Mendelian Inheritance in Man (OMIM), and Gene Expression Omnibus (GEO) databases. CHSC-CIS intersection targets were identified by matching the two, and prediction and analysis of biological functions and pathways of intersection targets was used the enrichments of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Furthermore, protein–protein interaction (PPI) network, herb-target, and compound-target network of CHSC-CIS were constructed by Cytoscape3.7.2, and herb-compound-pathway network was drawn with Sankey diagram. Finally, AutoDock was used for molecular docking verification, and identifying the active binding sites in target proteins. Results: A total of 293 putative targets were obtained from 62 active compounds in CHSC. Among them, 209 targets were related to CIS. PPI network showed that the top 16 key targets were RELA, JUN, FOS, MAPK1, AKT1, etc. KEGG pathway enrichment analysis demonstrated that CHSC was enriched in PI3K-Akt, MAPK, and TNF signaling pathways. In addition, GO enrichment analysis showed the significant enrichment of CHSC in the following categories: kinase binding, cellular response to nitrogen compound, etc. Network topology analysis showed that quercetin, luteolin, kaempferol, etc., were the key components in CHSC. Finally, molecular docking studies suggested that the active components in CHSC had a good binding ability with the key targets. Conclusions: Our study demonstrated that CHSC exerted the effect in treating CIS by the characteristics of multi-target and multi-pathway, thereby providing a theoretical basis for further study of the effective components and mechanism of CHSC in the treatment of CIS.

show abstract

Astroglial N‐myc downstream‐regulated gene 2 protects the brain from cerebral edema induced by stroke

Cited by 15 publications

References 77 publications

Hyponatremia Is Associated With Post-thrombolysis Hemorrhagic Transformation and Poor Clinical Outcome in Ischemic Stroke Patients

Hyponatremia Is Associated With Post-thrombolysis Hemorrhagic Transformation and Poor Clinical Outcome in Ischemic Stroke Patients

N-Myc Downstream-Regulated Gene 2 (Ndrg2): A Critical Mediator of Estrogen-Induced Neuroprotection Against Cerebral Ischemic Injury

Uncovering the Mechanism of Chuanhong Stroke Capsule in the Treatment of Stroke Based on Network Pharmacology and Molecular Docking Technology

Contact Info

Product

Resources

About