Curcumol ameliorates neuroinflammation after cerebral ischemia–reperfusion injury via affecting microglial polarization and Treg/Th17 balance through Nrf2/HO-1 and NF-κB signaling

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Июнь 24, 2024

Abstract Neuroinflammation caused by microglia and other immune cells plays pivotal role in cerebral ischemia/reperfusion injury recovery. Modulating microglial polarization or Treg/Th17 balance from pro-inflammatory phenotype to anti-inflammatory are promising strategies for the treatment of ischemia. Curcumol has potential fight against oxidative stress inflammation, but whether it protective effect ischemia is uncertain. In present study, was induced C57BL/6 mice via middle artery occlusion (MCAO). MCAO were treated with curcumol 7 days, then post-stroke ischemic injury, neurological deficits, brain leukocyte infiltration evaluated TTC staining, behavioural tests, flow cytometry, western blot immunofluorescence. We found that poststroke administration reduced infarct volume, attenuated neuronal damage improved motor function recovery mice. skewed toward vivo after oxygen-glucose deprivation reoxygenation (OGD/R) vitro. addition, local T cell impaired balance. inhibited ROS production regulated Nrf2/HO-1 NF-κB signaling microglia. Finally, inhibiting activating abrogated influence on polarization. conclusion, neuroinflammation modulating through signaling. might be a strategy stroke patients.

Язык: Английский

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Activation of LXRs alleviates neuropathic pain-induced cognitive dysfunction by modulation of microglia polarization and synaptic plasticity via PI3K/AKT pathway

Inflammation Research, Год журнала: 2024, Номер 73(2), С. 157 - 174

Опубликована: Янв. 6, 2024

Язык: Английский

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Microglial heterogeneity in the ischemic stroke mouse brain of both sexes

Genome Medicine, Год журнала: 2024, Номер 16(1)

Опубликована: Авг. 2, 2024

Ischemic stroke elicits a complex and sustained immune response in the brain. Immunomodulatory treatments have long held promise for improving outcomes, yet none succeeded clinical setting. This lack of success is largely due to our incomplete understanding how cells respond stroke. The objective current study was dissect effect permanent on microglia, resident within brain parenchyma. A middle cerebral artery occlusion (pMCAO) model used induce ischemic young male female mice. Microglia were sorted from fluorescence reporter mice after pMCAO or sham surgery then subjected single-cell RNA sequencing analysis. Various methods, including flow cytometry, situ hybridization, immunohistochemistry, whole-brain imaging, bone marrow transplantation, also employed microglial Stroke outcomes evaluated by infarct size behavioral tests. First, we showed morphologic spatial changes microglia We performed analysis isolated both sexes. data indicate no major sexual dimorphism Notably, identified seven potential stroke-associated clusters, four clusters characterized disease-associated microglia-like signature, highly proliferative state, macrophage-like profile, an interferon (IFN) respectively. Importantly, provided evidence that cluster may represent long-sought stroke-induced subpopulation with increased CD45 expression. Lastly, given IFN-responsive subset constitutes most prominent population brain, fludarabine pharmacologically target STAT1 signaling found treatment improved long-term outcome. Our findings shed new light heterogeneity pathology underscore targeting specific populations effective therapies.

Язык: Английский

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The role of microglial activation on ischemic stroke: Modulation by fibroblast growth factors

Cytokine & Growth Factor Reviews, Год журнала: 2023, Номер 74, С. 122 - 133

Опубликована: Июль 31, 2023

Stroke is one of the devastating clinical conditions that causes death and permanent disability. Its occurrence reduction oxygen glucose supply, resulting in events such as inflammatory response, oxidative stress, apoptosis brain. Microglia are brain-resident immune cells central nervous system (CNS) exert diverse roles respond to pathological process after an ischemic insult. The discovery fibroblast growth factors (FGFs) mammals, resulted findings they can treat experimental models stroke animals effectively. FGFs function homeostatic control hormones involved metabolism, also regulate secretion proinflammatory (M1) anti-inflammatory (M2) cytokines stroke. In this review, we outline current evidence microglia activation focusing on its ability exacerbate damage or repair tissue. Also, our review sheds light pharmacological actions multiple targets microglial modulation highlighted their theoretical molecular mechanisms provide possible therapeutic targets, well limitations for treatment DATA AVAILABILITY: Not applicable.

Язык: Английский

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The impact of neuroinflammation on neuronal integrity

Immunological Reviews, Год журнала: 2024, Номер 327(1), С. 8 - 32

Опубликована: Окт. 1, 2024

Neuroinflammation, characterized by a complex interplay among innate and adaptive immune responses within the central nervous system (CNS), is crucial in responding to infections, injuries, disease pathologies. However, dysregulation of neuroinflammatory response could significantly affect neurons terms function structure, leading profound health implications. Although tremendous progress has been made understanding relationship between processes alterations neuronal integrity, specific implications concerning both structure have not extensively covered, with exception perspectives on glial activation neurodegeneration. Thus, this review aims provide comprehensive overview multifaceted interactions key inflammatory players, exploring mechanisms through which inflammation influences functionality structural integrity CNS. Further, it will discuss how these lead impairment functions architecture highlight consequences caused dysregulated functions, such as cognitive dysfunction mood disorders. By integrating insights from recent research findings, enhance our landscape set stage for future interventions that transform current approaches preserve CNS-related conditions.

Язык: Английский

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Long Noncoding RNA ISA1 Protects Against Ischemic Brain Damage by Promoting the Transformation of Microglia Toward Anti-inflammatory Phenotype via the SOCS3/JAK2/STAT3 Pathway

Neurochemical Research, Год журнала: 2025, Номер 50(2)

Опубликована: Фев. 1, 2025

Язык: Английский

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Neuroinflammation aggravated by traumatic brain injury at high altitude is reversed by L-serine via NFAT1-mediated microglial polarization

Frontiers in Cellular Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Апрель 14, 2023

Traumatic brain injury (TBI) is one of the main causes disability and death, especially in plateau areas, where degree often more serious than plain areas. It likely that high altitude (HA) aggravates neuroinflammation; however, prior studies are limited. This study was designed to evaluate effects HA on TBI neuroprotective underlying mechanisms L-serine against at (HA-TBI). In vivo experiments, wild-type mice with Nfat1 (Nfat1-/- ) deficiency C57BL/6 background were kept a hypobaric chamber for 3 days under simulated conditions 4,000 m, 6,000 m 8,000 above sea level. After leaving chamber, standardized model established immediately. Mice then intraperitoneally injected (342 mg.kg-1) 2 h after daily 5 days. Behavioral tests histological analysis assessed different time points post induction. vitro, we applied primary cultured microglia hypoxia treatment (1% O2 24 h). The major findings include following: (1) increasing altitude, neurological function decreased, damage cerebral gray matter white became significant, (2) significantly improved sensorimotor mice, reversed increase lesion volume, promoted renovation tissue HA-TBI, (3) decreased activation polarization toward protective M2 phenotype both (4) suppressed expression NFAT1 HA-TBI inhibited hypoxia, (5) knockout inflammatory reaction caused by excessive microglia, lost its effect mice. present suggests also increases altitude. As an endogenous amino acid, may be agent suppression potential therapy neuroinflammation future.

Язык: Английский

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Brain microvascular endothelial cell‐derived exosomes transmitting circ_0000495 promote microglial M1‐polarization and endothelial cell injury under hypoxia condition

The FASEB Journal, Год журнала: 2024, Номер 38(2)

Опубликована: Янв. 9, 2024

Abstract Human brain microvascular endothelial cells (HBMVECs) and microglia play critical roles in regulating cerebral homeostasis during ischemic stroke. However, the role of HBMVECs‐derived exosomes polarization after stroke remains unknown. We isolated (Exos) from oxygen glucose deprivation (OGD)‐exposed HBMVECs, before added them into microglia. Microglia markers were tested using RT‐qPCR or flow cytometry. Inflammatory cytokines measured with ELISA. Endothelial cell damage was assessed by viability, apoptosis, apoptosis‐related proteins, oxidative stress, angiogenic activity CCK‐8, cytometry, western blot, ELISA, tube formation assay, respectively. also established middle artery occlusion (MCAO) mice model to examine function circ_0000495 on vivo. Our study found that HBMVECs‐Exos reduced M2 (IL‐10, CD163, CD206), increased M1 (TNF‐α, IL‐1β, IL‐12), CD86‐positive cells, inflammatory (TNF‐α IL‐1β), indicating promotion microglial M1‐polarization. Microglial M1‐polarization induced viability promoted apoptosis revealing aggravation damage. silencing inhibited HBMVECs‐Exos‐induced alterations. Mechanistically, adsorbed miR‐579‐3p upregulate toll‐like receptor 4 (TLR4) microglia; suppressed alterations via declining TLR4; furthermore, Yin Yang 1 (YY1) transcriptionally activated HBMVECs. Importantly, aggravated injury vivo activating TLR4/nuclear factor‐κB (NF‐κB) pathway. Collectively, OGD‐treated transmitted regulate miR‐579‐3p/TLR4/NF‐κB axis microglia, thereby facilitating

Язык: Английский

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Physical exercise regulates microglia in health and disease

Frontiers in Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Июнь 7, 2024

There is a well-established link between physical activity and brain health. As such, the effectiveness of exercise as therapeutic strategy has been explored in variety neurological contexts. To determine extent to which could be most beneficial under different circumstances, studies are needed uncover underlying mechanisms behind benefits activity. Interest grown understanding how can regulate microglia, resident immune cells central nervous system. Microglia key mediators neuroinflammatory processes play role maintaining homeostasis healthy pathological settings. Here, we explore evidence suggesting that potential microglia various animal models. We emphasize areas where future research contribute uncovering engaging exercise.

Язык: Английский

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Beyond wrecking a wall: revisiting the concept of blood–brain barrier breakdown in ischemic stroke

Neural Regeneration Research, Год журнала: 2024, Номер 20(7), С. 1944 - 1956

Опубликована: Июль 29, 2024

The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system peripheral circulation. It tightly modulates ion transport nutrient influx, while restricting entry of harmful factors, selectively limiting migration immune cells, thereby maintaining brain homeostasis. Despite well-established association between disruption most neurodegenerative/neuroinflammatory diseases, much remains unknown about factors influencing its physiology mechanisms underlying breakdown. Moreover, role breakdown in translational failure therapies for disorders is just starting to be understood. This review aims revisit this concept “blood–brain breakdown,” delving into controversial aspects, prevalent challenges, knowledge gaps concerning lack integrity. By moving beyond oversimplistic dichotomy an “open”/“bad” or “closed”/“good” barrier, our objective provide more comprehensive insight dynamics, identify novel targets and/or therapeutic approaches aimed at mitigating dysfunction. Furthermore, review, we advocate considering diverse time- location-dependent alterations which go tight-junction endothelial cell breakdown, illustrated through dynamics ischemic stroke as case study. Through exploration, seek underscore complexity dysfunction implications pathogenesis therapy diseases.

Язык: Английский

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