Microglia-Mediated Neuroinflammation: A Potential Target for the Treatment of Cardiovascular Diseases

Journal of Inflammation Research, Journal Year: 2022, Volume and Issue: Volume 15, P. 3083 - 3094

Published: May 1, 2022

Abstract: Microglia are tissue-resident macrophages of the central nervous system (CNS). In CNS, microglia play an important role in monitoring and intervention synaptic neuron-level activities. Interventions targeting have been shown to improve prognosis various neurological diseases. Recently, studies observed activation different cardiovascular addition, approaches that regulate activity modulate incidence progression The change autonomic after neuroinflammation may be a potential intermediate link between Here, this review, we will discuss recent updates on regulatory hypertension, myocardial infarction ischemia/reperfusion injury. We propose serve as neuroimmune modulators targets for Keywords: neuroimmune, system, central-peripheral crosstalk, sympathetic

Language: Английский

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Inhibiting HMGB1-RAGE axis prevents pro-inflammatory macrophages/microglia polarization and affords neuroprotection after spinal cord injury

Journal of Neuroinflammation, Journal Year: 2020, Volume and Issue: 17(1)

Published: Oct. 9, 2020

Abstract Background Spinal cord injury (SCI) favors a persistent pro-inflammatory macrophages/microglia-mediated response with only transient appearance of anti-inflammatory phenotype immune cells. However, the mechanisms controlling this special sterile inflammation after SCI are still not fully elucidated. It is known that damage-associated molecular patterns (DAMPs) released from necrotic cells can trigger severe inflammation. High mobility group box 1(HMGB1), ubiquitously expressed DNA binding protein, an identified DAMP, and our previous study demonstrated reactive astrocytes could undergo necroptosis release HMGB1 in mice. The present aimed to explore effects possible mechanism HMGB1on macrophages/microglia polarization, as well neuroprotective by inhibition SCI. Methods In study, expression concentration was determined qRT-PCR, ELISA, immunohistochemistry. Glycyrrhizin applied inhibit HMGB1, while FPS-ZM1 suppress receptor for advanced glycation end products (RAGE). polarization vitro vivo detected immunostaining, western blot. lesion area GFAP staining, neuronal survival examined Nissl staining. Luxol fast blue (LFB) DAB blot were adopted evaluate myelin loss. Basso-Beattie-Bresnahan (BBB) scoring rump-height Index (RHI) assay locomotor functional recovery. Results Our data showed be elevated necroptotic induce microglia through RAGE-nuclear factor-kappa B (NF-κB) pathway. We further inhibiting or RAGE effectively decreased numbers detrimental increased Furthermore, significantly loss demyelination, improved recovery Conclusions implicated HMGB1-RAGE axis contributed dominant response, pathway afforded neuroprotection Thus, therapies designed modulate microenvironment based on cascade might prospective treatment

Language: Английский

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A DAMP-scavenging, IL-10-releasing hydrogel promotes neural regeneration and motor function recovery after spinal cord injury

Biomaterials, Journal Year: 2021, Volume and Issue: 280, P. 121279 - 121279

Published: Nov. 24, 2021

Language: Английский

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Glial Cell-Mediated Neuroinflammation in Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10572 - 10572

Published: Sept. 12, 2022

Alzheimer's disease (AD) is a progressive neurodegenerative disorder; it the most common cause of dementia and has no treatment. It characterized by two pathological hallmarks, extracellular deposits amyloid beta (Aβ) intraneuronal Neurofibrillary tangles (NFTs). Yet, those hallmarks do not explain full pathology seen with AD, suggesting involvement other mechanisms. Neuroinflammation could offer another explanation for progression disease. This review provides an overview recent advances on role immune cells' microglia astrocytes in neuroinflammation. In become reactive several mechanisms leading to release proinflammatory cytokines that further neuronal damage. We then provide updates neuroinflammation diagnostic markers investigational therapeutics currently clinical trials target

Language: Английский

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IL-17 crosses the blood–brain barrier to trigger neuroinflammation: a novel mechanism in nitroglycerin-induced chronic migraine

The Journal of Headache and Pain, Journal Year: 2022, Volume and Issue: 23(1)

Published: Jan. 3, 2022

Chronic migraine places a disabling burden on patients, which is extensively modeled by the nitroglycerin (NTG)-treated animal model. Although NF-κB pathway involved in an increase CGRP levels and activation of trigeminal system NTG model, relationship between neuroinflammation remains unclear. This study aimed to optimize chronic rat model with hyperalgesia ethological capacity for estimating therapies further explore underlying mechanism NTG-induced migraine.Rats were administered different doses s.c. daily or every 2 d; 30 min h later, mechanical threshold was tested. After 9 d, rats injected EB Cy5.5 permeability assay. The other animals sacrificed, then, brainstem caudal ganglion removed test CGRP, c-Fos NOS activity; Cytokines tissue serum measured ELISA; blood-brain barrier (BBB)-related indicators analyzed using western blotting. Immunohistochemistry performed observe microglial polarization IL-17A+ T cell migration medulla oblongata.NTG (10 mg/kg, s.c., d total 5 injections) optimal condition, resulting progressive behavior. TNC increases cytokines, observed, these changes alleviated ibuprofen. Furthermore, administration increased BBB altering functional proteins (RAGE, LRP1, AQP4 MFSD2A) structural (ZO-1, Occludin VE-cadherin-2) peripheral IL-17A permeation into oblongata, activating microglia neuroinflammation, eventually causing attack.This confirmed that condition provoke migraine, observable migraine-like crossed triggering through microglia-mediated neuroinflammation. process novel suggesting might be target treatment migraine.

Language: Английский

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HMGB1: A New Target for Ischemic Stroke and Hemorrhagic Transformation

Translational Stroke Research, Journal Year: 2024, Volume and Issue: unknown

Published: May 14, 2024

Abstract Stroke in China is distinguished by its high rates of morbidity, recurrence, disability, and mortality. The ultra-early administration rtPA essential for restoring perfusion acute ischemic stroke, though it concurrently elevates the risk hemorrhagic transformation. High-mobility group box 1 (HMGB1) emerges as a pivotal player neuroinflammation after brain ischemia ischemia–reperfusion. Released passively necrotic cells actively secreted, including direct secretion HMGB1 into extracellular space packaging intracellular vesicles immune cells, glial platelets, endothelial represents prototypical damage-associated molecular pattern (DAMP). It intricately involved pathogenesis atherosclerosis, thromboembolism, detrimental inflammation during early phases stroke. Moreover, significantly contributes to neurovascular remodeling functional recovery later stages. Significantly, mediates transformation facilitating neuroinflammation, directly compromising integrity blood–brain barrier, enhancing MMP9 through interaction with rtPA. As systemic inflammatory factor, also implicated post-stroke depression an elevated stroke-associated pneumonia. role extends influencing polarizing various subtypes cells. This includes mediating excitotoxicity due excitatory amino acids, autophagy, release, NET formation, autocrine trophic pathways. Given multifaceted role, recognized crucial therapeutic target prognostic marker stroke In this review, we summarize structure redox properties, pathways, regulation cell activity, pathophysiological mechanisms hemorrhage HMGB1, which will pave way developing new neuroprotective drugs, reduction expansion thrombolysis time window.

Language: Английский

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The Role of Microglia in Brain Metastases: Mechanisms and Strategies

Aging and Disease, Journal Year: 2024, Volume and Issue: 15(1), P. 169 - 169

Published: Jan. 1, 2024

Brain metastases and related complications are one of the major fatal factors in cancer. Patients with breast cancer, lung melanoma at a high risk developing brain metastases. However, mechanisms underlying metastatic cascade remain poorly understood. Microglia, resident macrophages parenchyma, involved multiple processes associated metastasis, including inflammation, angiogenesis, immune modulation. They also closely interact cancer cells, astrocytes, other cells. Current therapeutic approaches against cancers, small-molecule drugs, antibody-coupled drugs (ADCs), immune-checkpoint inhibitors (ICIs), have compromised efficacy owing to impermeability blood-brain barrier (BBB) complex microenvironment. Targeting microglia is strategies for treating In this review, we summarize multifaceted roles highlight them as potential targets future interventions.

Language: Английский

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HMGB1 mediates epithelial-mesenchymal transition and fibrosis in silicosis via RAGE/β-catenin signaling

Chemico-Biological Interactions, Journal Year: 2025, Volume and Issue: unknown, P. 111385 - 111385

Published: Jan. 1, 2025

Language: Английский

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Microglia in Alzheimer’s Disease: A Target for Therapeutic Intervention

Frontiers in Cellular Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Nov. 24, 2021

Alzheimer’s disease (AD) is one of the most common types age-related dementia worldwide. In addition to extracellular amyloid plaques and intracellular neurofibrillary tangles, dysregulated microglia also play deleterious roles in AD pathogenesis. Numerous studies have demonstrated that unbridled microglial activity induces a chronic neuroinflammatory environment, promotes β-amyloid accumulation tau pathology, impairs microglia-associated mitophagy. Thus, targeting may pave way for new therapeutic interventions. This review provides thorough overview pathophysiological role illustrates potential avenues microglia-targeted therapies, including modification, immunoreceptors, anti-inflammatory drugs.

Language: Английский

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Human Umbilical Cord Mesenchymal Stem Cell‐Derived Exosomes Attenuate Oxygen‐Glucose Deprivation/Reperfusion‐Induced Microglial Pyroptosis by Promoting FOXO3a‐Dependent Mitophagy

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Background . Mesenchymal stem cell‐derived exosomes (MSC‐exos) have been recognized as a promising therapeutic strategy for neonatal hypoxic‐ischemic brain damage (HIBD). Recently, microglial pyroptosis was shown to play vital role in the progression of HIBD. However, whether MSC‐exos improve HIBD by regulating remains unknown. Methods. Exosomes were isolated from human umbilical cord mesenchymal cells (huMSCs) and identified transmission electron microscopy (TEM), western blot, nanoparticle tracking analysis (NTA). BV‐2 subjected oxygen‐glucose deprivation/reoxygenation (OGD/R) induce ischemia/reperfusion (I/R) vitro CCK‐8, ELISA, Hoechst 33342/PI double staining performed detect cells. Conditioned medium (CM) exposed different treatments used investigate its effect on neuronal injury. Moreover, 3‐methyladenine (3‐MA) mitochondrial division inhibitor‐1 (mdi‐1) verify involvement mitophagy protection against OGD/R‐induced Finally, FOXO3a siRNA MSC‐exo‐induced inhibition. Results huMSCs successfully extracted. In OGD/R‐exposed cells, increased cell viability decreased expression NLRP3, cleaved caspase‐1, GSDMD‐N well release IL‐1 β IL‐18. Compared with CM treated PBS, significantly SH‐SY5Y LDH release. also TOM20 COX IV Additionally, 3‐MA mdi‐1 attenuated inhibition MSC‐exo treatment. Furthermore, partially abolished neuroprotective induced Conclusions Our findings demonstrated that enhance mitophagy, therefore protecting microglia I/R‐induced alleviating subsequent

Language: Английский

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