Phagocytic microglia and macrophages in brain injury and repair

CNS Neuroscience & Therapeutics, Год журнала: 2022, Номер 28(9), С. 1279 - 1293

Опубликована: Июнь 25, 2022

Phagocytosis is the cellular digestion of extracellular particles, such as pathogens and dying cells, a key element in evolution central nervous system (CNS) disorders. Microglia macrophages are professional phagocytes CNS. By clearing toxic debris reshaping matrix, microglia/macrophages help pilot brain repair functional recovery process. However, CNS resident invading immune cells can also magnify tissue damage by igniting runaway inflammation phagocytosing stressed-but viable-neurons.

Язык: Английский

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Microglia-mediated neuroinflammation and neuroplasticity after stroke

Frontiers in Cellular Neuroscience, Год журнала: 2022, Номер 16

Опубликована: Авг. 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.

Язык: Английский

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Lysosomal acidification dysfunction in microglia: an emerging pathogenic mechanism of neuroinflammation and neurodegeneration

Journal of Neuroinflammation, Год журнала: 2023, Номер 20(1)

Опубликована: Авг. 5, 2023

Microglia are the resident innate immune cells in brain with a major role orchestrating responses. They also provide frontline of host defense central nervous system (CNS) through their active phagocytic capability. Being professional phagocyte, microglia participate and autophagic clearance cellular waste debris as well toxic protein aggregates, which relies on optimal lysosomal acidification function. Defective microglial leads to impaired functions result perpetuation neuroinflammation progression neurodegeneration. Reacidification lysosomes has been shown reverse neurodegenerative pathology Alzheimer's disease. In this review, we summarize key factors mechanisms contributing impairment associated dysfunction microglia, how these defects contribute We further discuss techniques monitor pH therapeutic agents that can reacidify under disease conditions. Finally, propose future directions investigate lysosome-mitochondria crosstalk neuron-glia interaction for more comprehensive understanding its broader CNS physiological pathological implications.

Язык: Английский

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Shared inflammatory glial cell signature after stab wound injury, revealed by spatial, temporal, and cell-type-specific profiling of the murine cerebral cortex

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 3, 2024

Traumatic brain injury leads to a highly orchestrated immune- and glial cell response partially responsible for long-lasting disability the development of secondary neurodegenerative diseases. A holistic understanding mechanisms controlling responses specific types their crosstalk is required develop an efficient strategy better regeneration. Here, we combine spatial single-cell transcriptomics chart transcriptomic signature injured male murine cerebral cortex, identify states different cells contributing this signature. Interestingly, distinct share large fraction injury-regulated genes, including inflammatory programs downstream innate immune-associated pathways Cxcr3 Tlr1/2. Systemic manipulation these decreases reactivity state associated with poor The functional relevance discovered shared highlights importance our resource enabling comprehensive analysis early events after injury.

Язык: Английский

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Astrocytic CXCL5 hinders microglial phagocytosis of myelin debris and aggravates white matter injury in chronic cerebral ischemia

Journal of Neuroinflammation, Год журнала: 2023, Номер 20(1)

Опубликована: Май 3, 2023

Chronic cerebral ischemia induces white matter injury (WMI) contributing to cognitive decline. Both astrocytes and microglia play vital roles in the demyelination remyelination processes, but underlying mechanism remains unclear. This study aimed explore influence of chemokine CXCL5 on WMI decline chronic mechanism.Bilateral carotid artery stenosis (BCAS) model was constructed mimic 7-10 weeks old male mice. Astrocytic Cxcl5 conditional knockout (cKO) mice were with overexpressing generated by stereotactic injection adeno-associated virus (AAV). evaluated magnetic resonance imaging (MRI), electron microscopy, histological staining western blotting. Cognitive function examined a series neurobehavioral tests. The proliferation differentiation oligodendrocyte progenitor cells (OPCs), phagocytosis analyzed via immunofluorescence staining, blotting or flow cytometry.CXCL5 significantly elevated corpus callosum (CC) serum BCAS model, mainly expressed astrocytes, cKO displayed improved performance. Recombinant (rCXCL5) had no direct effect OPCs vitro. specific overexpression aggravated induced ischemia, while depletion counteracted this effect. remarkably hindered microglial myelin debris, which rescued inhibition receptor C-X-C motif 2 (CXCR2).Our revealed that astrocyte-derived inhibiting suggesting novel astrocyte-microglia circuit mediated CXCL5-CXCR2 signaling ischemia.

Язык: Английский

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Resolvin D1 reprograms energy metabolism to promote microglia to phagocytize neutrophils after ischemic stroke

Cell Reports, Год журнала: 2023, Номер 42(6), С. 112617 - 112617

Опубликована: Июнь 1, 2023

Neutrophil aggregation and clearance are important factors affecting neuroinflammatory injury during acute ischemic stroke. Emerging evidence suggests that energy metabolism is essential for microglial functions, especially phagocytosis, which determines the degree of brain injury. Here, we demonstrate Resolvin D1 (RvD1), a lipid mediator derived from docosahexaenic acid (DHA), promotes phagocytosis neutrophils by microglia, thereby reducing neutrophil accumulation in alleviating neuroinflammation brain. Further studies reveal RvD1 reprograms glycolysis to oxidative phosphorylation (OXPHOS), providing sufficient phagocytosis. Moreover, enhances glutamine uptake stimulates glutaminolysis support OXPHOS boost ATP production depending on adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activation. Overall, our results promote after These findings may guide perspectives stroke therapy modulating immunometabolism.

Язык: Английский

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Blocking the MIF-CD74 axis augments radiotherapy efficacy for brain metastasis in NSCLC via synergistically promoting microglia M1 polarization

Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)

Опубликована: Апрель 29, 2024

Abstract Background Brain metastasis is one of the main causes recurrence and death in non-small cell lung cancer (NSCLC). Although radiotherapy local therapy for brain metastasis, it inevitable that some cells become resistant to radiation. Microglia, as macrophages colonized brain, play an important role tumor microenvironment. Radiotherapy could activate microglia polarize into both M1 M2 phenotypes. Therefore, searching crosstalk molecules within microenvironment can specifically regulate polarization a potential strategy improving radiation resistance. Methods We used databases detect expression MIF NSCLC its relationship with prognosis. analyzed effects targeted blockade MIF/CD74 axis on function during using flow cytometry. The mouse model was assess effect growth metastasis. Result Our findings reveals macrophage migration inhibitory factor (MIF) highly expressed associated prognosis NSCLC. Mechanistically, we demonstrated CD74 inhibition reversed radiation-induced AKT phosphorylation promoted combination Additionally, blocking MIF-CD74 interaction between polarization. Furthermore, improved hypoxia decrease HIF-1α dependent secretion by enhanced radiosensitivity via synergistically promoting vivo. Conclusions study revealed targeting synergized

Язык: Английский

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Dysregulated brain-gut axis in the setting of traumatic brain injury: review of mechanisms and anti-inflammatory pharmacotherapies

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Май 10, 2024

Abstract Traumatic brain injury (TBI) is a chronic and debilitating disease, associated with high risk of psychiatric neurodegenerative diseases. Despite significant advancements in improving outcomes, the lack effective treatments underscore urgent need for innovative therapeutic strategies. The brain-gut axis has emerged as crucial bidirectional pathway connecting gastrointestinal (GI) system through an intricate network neuronal, hormonal, immunological pathways. Four main pathways are primarily implicated this crosstalk, including systemic immune system, autonomic enteric nervous systems, neuroendocrine microbiome. TBI induces profound changes gut, initiating unrestrained vicious cycle that exacerbates axis. Alterations gut include mucosal damage malabsorption nutrients/electrolytes, disintegration intestinal barrier, increased infiltration cells, dysmotility, dysbiosis, enteroendocrine cell (EEC) dysfunction disruption (ENS) (ANS). Collectively, these further contribute to neuroinflammation neurodegeneration via gut-brain In review article, we elucidate roles various anti-inflammatory pharmacotherapies capable attenuating dysregulated inflammatory response along TBI. These agents hormones such serotonin, ghrelin, progesterone, ANS regulators beta-blockers, lipid-lowering drugs like statins, flora modulators probiotics antibiotics. They attenuate by targeting distinct both post-TBI. exhibit promising potential mitigating inflammation enhancing neurocognitive outcomes patients.

Язык: Английский

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Maresin-1 promotes neuroprotection and modulates metabolic and inflammatory responses in disease-associated cell types in preclinical models of Multiple Sclerosis

Journal of Biological Chemistry, Год журнала: 2025, Номер unknown, С. 108226 - 108226

Опубликована: Янв. 1, 2025

Язык: Английский

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Oligodendrocytes in central nervous system diseases: the effect of cytokine regulation

Neural Regeneration Research, Год журнала: 2024, Номер unknown

Опубликована: Янв. 8, 2024

Abstract Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines involved nearly every aspect of cellular functions such as migration, survival, proliferation, differentiation. Oligodendrocytes the myelin-forming cells central nervous system play critical roles conduction action potentials, supply metabolic components for axons, other functions. Emerging evidence suggests that both oligodendrocytes oligodendrocyte precursor vulnerable to released under pathological conditions. This review mainly summarizes effects on lineage A comprehensive understanding contributes our diseases offers insights into treatment strategies.

Язык: Английский

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