Peripheral inflammation and blood–brain barrier disruption: effects and mechanisms

CNS Neuroscience & Therapeutics, Journal Year: 2020, Volume and Issue: 27(1), P. 36 - 47

Published: Dec. 30, 2020

Abstract The blood–brain barrier (BBB) is an important physiological that separates the central nervous system (CNS) from peripheral circulation, which contains inflammatory mediators and immune cells. BBB regulates cellular molecular exchange between blood vessels brain parenchyma. Normal functioning of crucial for homeostasis proper function brain. It has been demonstrated inflammation can disrupt by various pathways, resulting in different CNS diseases. Recently, clinical research also showed complications following SARS‐CoV‐2 infection chimeric antigen receptor (CAR)‐T cell therapy, both lead to a cytokine storm circulation. Therefore, elucidation mechanisms underlying disruption induced will provide basis protecting context exacerbated In present review, we first summarize properties makes immune‐privileged organ. We then discuss relevance inflammation‐induced Finally, elaborate factors BBB.

Language: Английский

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Microglia: Agents of the CNS Pro-Inflammatory Response

Cells, Journal Year: 2020, Volume and Issue: 9(7), P. 1717 - 1717

Published: July 17, 2020

The pro-inflammatory immune response driven by microglia is a key contributor to the pathogenesis of several neurodegenerative diseases. Though research spans over century, last two decades have increased our understanding exponentially. Here, we discuss phenotypic transformation from homeostatic towards reactive microglia, initiated specific ligand binding pattern recognition receptors including toll-like receptor-4 (TLR4) or triggering expressed on myeloid cells-2 (TREM2), as well signaling pathways triggered such caspase-mediated response. Additionally, new disciplines epigenetics and immunometabolism provided us with more holistic view how changes in DNA methylation, microRNAs, metabolome may influence This review aimed current knowledge different angles, recent highlights role exosomes spreading neuroinflammation emerging techniques positron emission tomography (PET) scanning use human generated induced pluripotent stem cells (iPSCs). Finally, also thoughts impact

Language: Английский

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Melatonin protects against ischemic stroke by modulating microglia/macrophage polarization toward anti‐inflammatory phenotype through STAT3 pathway

CNS Neuroscience & Therapeutics, Journal Year: 2019, Volume and Issue: 25(12), P. 1353 - 1362

Published: Dec. 1, 2019

Microglia and infiltrated macrophages play important roles in inflammatory processes after ischemic stroke. Modulating microglia/macrophage polarization from pro-inflammatory phenotype to anti-inflammatory state has been suggested as a potential therapeutic approach the treatment of Melatonin shown be neuroprotective experimental stroke models. However, effect melatonin on microglia underlying mechanisms remain unknown.In vivo, cerebral ischemia was induced by distal middle artery occlusion (dMCAO) C57BL/6J mice. injected intraperitoneally (20 mg/kg) at 0 24 hours ischemia. In vitro, microglial cell line BV2 stimulated with conditioned media (CM) collected oxygen-glucose deprivation (OGD) challenged neuronal Neuro-2a (N2a). Real-time PCR utilized detect mRNA expression markers. Activation signal transducer activator transcription 3 (STAT3) pathway determined Western blot phosphorylated STAT3 (pSTAT3). A neuron-microglia co-culture system used determine whether can inhibit neurotoxic post-OGD neurons.Melatonin reduced brain infarct improved neurological functions days dMCAO, which accompanied decreased markers increased brain. vitro studies confirmed that directly inhibited responses cells upon exposure OGD neuron CM. The possessing exacerbated N2a death, whereas such effect. Further, enhanced otherwise pSTAT3 treated blockade significantly shift.Melatonin ameliorates damage least partially through shifting polarity STAT3-dependent manner.

Language: Английский

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Curcumin Ameliorates White Matter Injury after Ischemic Stroke by Inhibiting Microglia/Macrophage Pyroptosis through NF‐κB Suppression and NLRP3 Inflammasome Inhibition

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

Published: Jan. 1, 2021

NLRP3 inflammasome-mediated pyroptosis is a proinflammatory programmed cell death pathway, which plays vital role in functional outcomes after stroke. We previously described the beneficial effects of curcumin against stroke-induced neuronal damage through modulating microglial polarization. However, impact on remains unknown. Here, stroke was modeled mice by middle cerebral artery occlusion (MCAO) for 60 minutes and treated with (150 mg/kg) intraperitoneally immediately reperfusion, followed daily administrations 7 days. Curcumin ameliorated white matter (WM) lesions brain tissue loss 21 days poststroke improved sensorimotor function 3, 10, Furthermore, significantly reduced number gasdermin D+ (GSDMD+) Iba1+ caspase-1+Iba1+ microglia/macrophage In vitro, lipopolysaccharide (LPS) ATP treatment used to induce primary microglia. Western blot revealed decrease pyroptosis-related proteins, e.g., GSDMD-N, cleaved caspase-1, NLRP3, IL-1β, IL-18, following vitro or vivo treatment. Mechanistically, both studies confirmed that inhibited activation NF-κB pathway. knocked down siRNA transfection markedly increased inhibitory responses, vivo. stereotaxic microinjection AAV-based shRNA WM lesion MCAO mice. Our study suggested damage, outcomes, attenuated pyroptosis, at least partially, suppression NF-κB/NLRP3 signaling further supporting as potential therapeutic drug

Language: Английский

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Microglial/Macrophage polarization and function in brain injury and repair after stroke

CNS Neuroscience & Therapeutics, Journal Year: 2021, Volume and Issue: 27(5), P. 515 - 527

Published: March 1, 2021

Abstract Stroke is a leading cause of disability and mortality, with limited treatment options. After stroke injury, microglia CNS‐resident macrophages are rapidly activated regulate neuropathological processes to steer the course functional recovery. To accelerate this recovery, can engulf dying cells clear irreparably‐damaged tissues, thereby creating microenvironment that more suitable for formation new neural circuitry. In addition, monocyte‐derived cross compromised blood‐brain barrier infiltrate injured brain. The specific functions myeloid lineage in brain injury repair diverse dependent on phenotypic polarization statuses. However, it remains be determined what degree CNS‐invading occupy different niches from microglia. review, we describe physiological characteristics developing adult We also review (a) activation after stroke, (b) molecular mechanisms control status, (c) contribution pathology versus repair. Finally, summarize current breakthroughs therapeutic strategies calibrate microglia/macrophage responses stroke.

Language: Английский

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Neurovascular Unit: A critical role in ischemic stroke

CNS Neuroscience & Therapeutics, Journal Year: 2021, Volume and Issue: 27(1), P. 7 - 16

Published: Jan. 1, 2021

Abstract Ischemic stroke (IS), a common cerebrovascular disease, results from sudden blockage of blood vessel in the brain, thereby restricting supply to area question, and making significantly negative impact on human health. Unfortunately, current treatments, that are mainly based recanalization occluded vessels, insufficient or inaccessible many patients. Recently, profound influence neurovascular unit (NVU) prognosis IS have become better understood; in‐depth studies NVU also provided novel approaches for treatment. In this article, we review intimate connections between changes outcomes, discuss possible new management strategies having practical significance IS. We concept NVU, as well its roles blood‐brain barrier regulation, cell preservation, inflammatory immune response, repair. Besides, summarize noncoding RNAs therapies targeting NVU. conclude both pathophysiological repair processes strongly associated with homeostatic state further research into directed at could expand range treatments available

Language: Английский

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Microglia-mediated neuroinflammation and neuroplasticity after stroke

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: Aug. 16, 2022

Stroke remains a major cause of long-term disability and mortality worldwide. The immune system plays an important role in determining the condition brain following stroke. As resident innate cells central nervous system, microglia are primary responders defense network covering entire parenchyma, exert various functions depending on dynamic communications with neurons, astrocytes, other neighboring under both physiological or pathological conditions. Microglia activation polarization is crucial for damage repair ischemic stroke, considered double-edged sword neurological recovery. can exist pro-inflammatory states promote secondary damage, but they also secrete anti-inflammatory cytokines neurotrophic factors facilitate recovery In this review, we focus mechanisms microglia-mediated neuroinflammation neuroplasticity after ischemia relevant potential microglia-based interventions stroke therapy.

Language: Английский

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Gastrodin regulates the TLR4/TRAF6/NF-κB pathway to reduce neuroinflammation and microglial activation in an AD model

Phytomedicine, Journal Year: 2024, Volume and Issue: 128, P. 155518 - 155518

Published: March 15, 2024

Language: Английский

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Substrate stiffness modulates bone marrow-derived macrophage polarization through NF-κB signaling pathway

Bioactive Materials, Journal Year: 2020, Volume and Issue: 5(4), P. 880 - 890

Published: June 30, 2020

The stiffness of the extracellular matrix (ECM) plays an important role in regulating cellular programming. However, mechanical characteristics ECM affecting cell differentiation are still under investigated. Herein, we aimed to study effect substrate on macrophage polarization. We prepared polyacrylamide hydrogels with different stiffness, respectively. After were confirmed have a good biocompatibility, bone marrow-derived macrophages (BMMs) from mice incubated hydrogels. With simulated by low BMMs displayed enhanced expression CD86 surface and production reactive oxygen species (ROS) cells, secreted more IL-1β TNF-α supernatant. On contrary, stressed medium expressed CD206, produced less ROS, IL-4 TGF-β. In vivo delivered subcutaneously mice, CD68

Language: Английский

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Microglial Polarization: Novel Therapeutic Strategy against Ischemic Stroke

Aging and Disease, Journal Year: 2021, Volume and Issue: 12(2), P. 466 - 466

Published: Jan. 1, 2021

Ischemic stroke, which is the second highest cause of death and leading disability, represents ~71% all strokes globally. Some studies have found that key elements pathobiology stroke immunity inflammation. Microglia are first line defense in nervous system. After activated microglia become a double-edged sword, with distinct phenotypic changes to deleterious M1 types neuroprotective M2 types. Therefore, ways promote microglial polarization toward phenotype after focus attention recent years. In this review, we discuss process polarization, summarize alternation signaling pathways epigenetic regulation control ischemic aiming find potential mechanisms by can be transformed into polarized phenotype.

Language: Английский

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