A comparative study of the neuroprotective effects of dl-3-n-butylphthalide and edaravone dexborneol on cerebral ischemic stroke rats

European Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 951, P. 175801 - 175801

Published: May 18, 2023

Language: Английский

---

miR-195 Has a Potential to Treat Ischemic and Hemorrhagic Stroke through Neurovascular Protection and Neurogenesis

Molecular Therapy — Methods & Clinical Development, Journal Year: 2019, Volume and Issue: 13, P. 121 - 132

Published: Jan. 9, 2019

Tissue plasminogen activator is the only U.S. FDA-approved therapy for ischemic stroke, while there no specific medication hemorrhagic stroke. Therefore, treatment of acute stroke continues to be a major unmet clinical need. We explored effects miR-195 on neurovascular protection and its potential in treating Using both cellular animal studies, we showed that miR-195's beneficial are mediated by four mechanisms: (1) anti-apoptosis injured neural cells directly suppressing Sema3A/Cdc42/JNK signaling, (2) regeneration promoting stem cell proliferation migration, (3) anti-inflammation blocking NF-kB pathway, (4) improvement endothelial functions. intravenously injected carried nanoparticles into rats with either or stage. The results reduced size brain damage improved functional recovery types rats. reduction volume could up 45% approximately 30% therapeutic window between onset 6 h. Our data demonstrated possesses become new drug treat

Language: Английский

---

Rho/ROCK Pathway and Noncoding RNAs: Implications in Ischemic Stroke and Spinal Cord Injury

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(21), P. 11573 - 11573

Published: Oct. 26, 2021

Ischemic strokes (IS) and spinal cord injuries (SCI) are major causes of disability. RhoA is a small GTPase protein that activates downstream effector, ROCK. The up-regulation the RhoA/ROCK pathway contributes to neuronal apoptosis, neuroinflammation, blood-brain barrier dysfunction, astrogliosis, axon growth inhibition in IS SCI. Noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) long noncoding (lncRNAs), were previously considered be non-functional. However, they have attracted much attention because play an essential role regulating gene expression physiological pathological conditions. There growing evidence ROCK inhibitors, fasudil VX-210, can reduce injury SCI animal models clinical trials. Recently, it has been reported miRNAs decreased SCI, while lncRNAs increased. Inhibiting Rho/ROCK with alleviates oxidative stress, Further studies required explore significance ncRNAs establish new strategies for preventing treating these devastating diseases.

Language: Английский

---

Noncoding RNA crosstalk in brain health and diseases

Neurochemistry International, Journal Year: 2021, Volume and Issue: 149, P. 105139 - 105139

Published: July 16, 2021

Language: Английский

---

Long non-coding RNA H19 expression and functional polymorphism rs217727 are linked to increased ischemic stroke risk

BMC Neurology, Journal Year: 2021, Volume and Issue: 21(1)

Published: Feb. 4, 2021

Abstract Background Efforts to identify potential biomarkers for the diagnosis of ischemic stroke (IS) are valuable. The H19 gene plays a functional role in increasing prevalence IS risk factors. We evaluated correlation between rs217727 polymorphism and expression level lncRNA with susceptibility among Iranian population. Methods Blood samples were collected from patients ( n = 114) controls 114). concentrated on pattern at different time points (i.e., 0–24, 24–48, 48–72 h after stroke). tetra-amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method was applied DNA genotyping. used quantitative real-time PCR evaluate levels. receiver operating characteristic (ROC) curve prognosis IS. Results rs217727polymorphism related co-dominant (OR 2.92, 95% CI 0.91–10.92, P 0.04) recessive models 2.80, 0.96–8.15, 0.04). significantly upregulated remained high 72 stroke. ROC curves showed that within first 24 onset might serve as biomarker early 79.49% sensitivity 80.00% specificity. small vessel occlusion (SVO) large-artery atherosclerosis (LAA) 3.74 3.34 times higher than undetermined (UD) subtype, respectively [OR CL (1.14–12.27) 0.030 OR (1.13–9.85) 0.029]. Conclusion is correlated susceptibility, levels SVO LAA patients. upregulation may be considered diagnostic population, but it cannot useful prognostic marker.

Language: Английский

---

MiRNA: Involvement of the MAPK Pathway in Ischemic Stroke. A Promising Therapeutic Target

Medicina, Journal Year: 2021, Volume and Issue: 57(10), P. 1053 - 1053

Published: Oct. 1, 2021

Ischemic stroke (IS) is a cerebrovascular disease with high rate of disability and mortality. It classified as the second leading cause death that arises from sudden occlusion small vessels in brain consequent lack oxygen nutrients tissue. Following an acute ischemic event, cascade events promotes activation multiple signaling pathways responsible for irreversible neuronal damage. The mitogen-activated protein kinase (MAPK) pathway transmits signals cell membrane to nucleus response different stimuli, regulating proliferation, differentiation, inflammation, apoptosis. Several lines evidence showed MAPK important regulator hemorrhagic cerebral vascular disease; indeed, it can impair blood–brain barrier (BBB) integrity exacerbate neuroinflammation through release pro-inflammatory mediators implementing neurovascular damage after stroke. This review aims illustrate miRNAs involved regulation IS, order highlight possible targets potential neuroprotective treatments. We also discuss some (miR), including miR-145, miR-137, miR-493, miR-126, are they modulate processes such apoptosis, neuroinflammation, neurogenesis, angiogenesis IS. To date, limited drug therapies available treatment IS; therefore, necessary implement preclinical clinical studies aimed at discovering novel therapeutic approaches minimize post-stroke neurological

Language: Английский

---

LncRNA MEG3: Potential stock for precision treatment of cardiovascular diseases

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 29, 2022

The prevalence and mortality rates of cardiovascular diseases are increasing, new treatment strategies urgently needed. From the perspective basic pathogenesis, occurrence development related to inflammation, apoptosis, fibrosis autophagy cardiomyocytes, endothelial cells other cells. involvement maternally expressed gene 3 (MEG3) in human disease processes has been increasingly reported. P53 PI3K/Akt important pathways by which MEG3 participates regulating cell apoptosis. directly or competitively binds with miRNA participate oxidative stress, endoplasmic reticulum EMT processes. LncRNA is mainly involved malignant tumors, metabolic diseases, immune system cerebrovascular etc., a variety pathological effects fibroblasts great clinical application potential prevention AS, MIRI, hypertension HF. This paper will review research progress aspects mechanism action, systemic point out its diseases. lncRNAs also play role In addition, lncRNA shown biomarker value, prognostic value therapeutic response measurement tumor We boldly speculate that emerging discipline heart disease.

Language: Английский

---

Advances in the detection of biomarkers for ischemic stroke

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 24, 2025

Ischemic stroke is a leading cause of mortality and morbidity globally. Prompt intervention essential for arresting disease progression minimizing central nervous system damage. Although imaging studies play significant role in diagnosing ischemic stroke, their high costs limited sensitivity often result diagnostic treatment delays. Blood biomarkers have shown considerable promise the diagnosis prognosis stroke. Serum markers, closely associated with pathophysiology, aid diagnosis, subtype identification, prediction progression, early neurological deterioration, recurrence. Their advantages are particularly pronounced due to low cost rapid results. Despite identification numerous candidate blood biomarkers, clinical application requires rigorous research thorough validation. This review focuses on various related including coagulation fibrinolysis-related factors, endothelial dysfunction inflammatory neuronal axonal injury exosomes circular RNAs other relevant molecules. It also summarizes latest methods techniques biomarker detection, aiming provide critical references key biomarkers.

Language: Английский

---

Long noncoding RNA MALAT1 promotes angiogenesis through the caveolin-1/VEGF pathway after cerebral ischemic injury

Neuroreport, Journal Year: 2025, Volume and Issue: 36(7), P. 350 - 363

Published: April 9, 2025

The long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) might protect against cerebral ischemic injury. This study explored MALAT1’s function in stroke and whether it acts through the caveolin-1/vascular endothelial growth factor (VEGF) pathway. A mouse model of middle artery occlusion/reperfusion (MCAO/R) a human brain microvascular cell (HBMEC) oxygen-glucose deprivation/reoxygenation (OGD/R) were established. Lentiviral vectors for MALAT1 knockdown, caveolin-1 overexpression used gene regulation studies. Neurological deficits, proliferation, apoptosis, viability, vitro angiogenesis, migration, expression related protein evaluated using Zea Longa five-point scale, VEGF receptor 2/CD34 double immunofluorescence, TdT-mediated dUTP nick end labeling staining, counting kit-8 assay, tube formation transwell quantitative real time PCR, western blot. In MCAO/R HBMEC OGD/R model, levels MALAT1, caveolin-1, significantly upregulated compared to control group. vivo, downregulation exacerbated injury as manifested by severe neurological larger infarct volume, increased decreased numbers 2+/CD34+ progenitor cells, VEGF. Conversely, partially reversed inhibition migration tubule downregulation, restored promotes angiogenesis after injury, likely part via caveolin-1/VEGF Thus, may serve potential therapeutic target stroke.

Language: Английский

---

Decoding immune cell dynamics in ischemic stroke: insights from single-cell RNA sequencing analysis

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: April 15, 2025

Background Ischemic stroke (IS) is a leading cause of adult disability worldwide. The inflammatory processes involved are complex, making it challenging to fully understand the pathological mechanisms IS. Phagocytosis plays an important role in eliminating neurotoxic or damaged neurons resulting from responses. This study employed bioinformatics methods analyze single-cell RNA sequencing (scRNA-seq) data investigate cell types and molecular biological Methods scRNA-seq for IS were obtained Gene Expression Omnibus (GEO). Following sample screening reprocessing, 5,582 single cells identified healthy controls patients with Uniform manifold approximation projection (UMAP) was utilized further explore cellular composition Functional enrichment analysis differentially expressed genes conducted identify transcriptional regulators, whereas developmental trajectories predicted uncover potential fate decisions. iTALK ligand-receptor axes within cell-type immune microenvironment Results Based on analysis, we four their associated subclusters, along exhibiting significant differential expression these subclusters. significantly enriched linked IS, while differentiation subpopulations different. Additionally, multiple receptor-ligand identified, indicating diverse interactions Conclusion demonstrated that phagocytosis critically influences disease progression. It also infarct cells. These findings provide valuable insights into underlying highlight pathways therapeutic intervention.

Language: Английский

---