Lipopolysaccharide-Induced Model of Neuroinflammation: Mechanisms of Action, Research Application and Future Directions for Its Use

Molecules, Journal Year: 2022, Volume and Issue: 27(17), P. 5481 - 5481

Published: Aug. 26, 2022

Despite advances in antimicrobial and anti-inflammatory therapies, inflammation its consequences still remain a significant problem medicine. Acute inflammatory responses are responsible for directly life-threating conditions such as septic shock; on the other hand, chronic can cause degeneration of body tissues leading to severe impairment their function. Neuroinflammation is defined an response central nervous system involving microglia, astrocytes, cytokines including chemokines. It considered important neurodegerative diseases, Alzheimer's disease, Parkinson's disease amyotrophic lateral sclerosis. Lipopolysaccharide (LPS) strong immunogenic particle present outer membrane Gram-negative bacteria. major triggering factor cascade bacteria infection. The use LPS pro-inflammatory agent well-known model applied both vivo vitro studies. This review offers summary pathogenesis associated with exposure, especially field neuroinflammation. Moreover, we analyzed different models utilized area neuroscience. paper presents recent knowledge focused new insights experimental model.

Language: Английский

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Role of Microglia and Astrocytes in Alzheimer’s Disease: From Neuroinflammation to Ca2+ Homeostasis Dysregulation

Cells, Journal Year: 2022, Volume and Issue: 11(17), P. 2728 - 2728

Published: Sept. 1, 2022

Alzheimer’s disease (AD) is the most common form of dementia worldwide, with a complex, poorly understood pathogenesis. Cerebral atrophy, amyloid-β (Aβ) plaques, and neurofibrillary tangles represent main pathological hallmarks AD brain. Recently, neuroinflammation has been recognized as prominent feature brain substantial evidence suggests that inflammatory response modulates progression. Additionally, dysregulation calcium (Ca2+) homeostasis represents another early factor involved in pathogenesis, intracellular Ca2+ concentration essential to ensure proper cellular neuronal functions. Although growing supports involvement mechanisms neurodegeneration-related processes, scant data are available on its contribution microglia astrocytes functioning, both health throughout continuum. Nevertheless, AD-related aberrant signalling crucially underpinning neuroinflammatory processes that, turn, impact function. In this light, we attempted provide an overview current understanding interactions between glia cells-mediated responses molecular AD.

Language: Английский

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Mitochondria Dysfunction and Neuroinflammation in Neurodegeneration: Who Comes First?

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 240 - 240

Published: Feb. 16, 2024

Neurodegenerative diseases (NDs) encompass an assorted array of disorders such as Alzheimer's disease, Parkinson's and amyotrophic lateral sclerosis, each characterised by distinct clinical manifestations underlying pathological mechanisms. While some cases have a genetic basis, many NDs occur sporadically. Despite their differences, these commonly feature chronic neuroinflammation hallmark. Consensus has recently been reached on the possibility that mitochondria dysfunction protein aggregation can mutually contribute to activation neuroinflammatory response thus onset progression disorders. In present review, we discuss contribution aetiology NDs, highlighting new potential therapeutic targets be identified tackle neurodegenerative processes alleviate pathologies.

Language: Английский

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The Impact of Microglia on Neurodevelopment and Brain Function in Autism

Biomedicines, Journal Year: 2024, Volume and Issue: 12(1), P. 210 - 210

Published: Jan. 17, 2024

Microglia, as one of the main types glial cells in central nervous system (CNS), are widely distributed throughout brain and spinal cord. The normal number function microglia very important for maintaining homeostasis CNS. In recent years, scientists have paid widespread attention to role Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder, patients with ASD severe deficits behavior, social skills, communication. Most previous studies on focused neuronal pathological changes, such increased cell proliferation, accelerated differentiation, impaired synaptic development, reduced spontaneous synchronous activity. Currently, more research has found that microglia, immune cells, can promote neurogenesis pruning maintain CNS homeostasis. They usually reduce unnecessary connections early life. Some researchers proposed many phenotypes may be caused by microglial abnormalities. Based this, we summarize ASD, focusing We aim clarify essential factors influenced explore possibility microglia-related pathways potential targets ASD.

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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The Crucial Role of the Blood–Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 386 - 386

Published: Jan. 9, 2025

The blood-brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from bloodstream into central nervous system (CNS). Neurodegenerative diseases such as Alzheimer's Parkinson's disease, well ischemic stroke, compromise integrity BBB. This leads to increased permeability infiltration harmful substances, thereby accelerating neurodegeneration. In this review, we explore mechanisms underlying BBB disruption, including oxidative stress, neuroinflammation, vascular dysfunction, loss tight junction integrity, in patients with neurodegenerative diseases. We discuss how breakdown contributes neurotoxicity, abnormal accumulation pathological proteins, all which exacerbate neuronal damage facilitate disease progression. Furthermore, potential therapeutic strategies aimed at preserving or restoring function, anti-inflammatory treatments, antioxidant therapies, approaches enhance integrity. Given role neurodegeneration, maintaining its represents promising approach slow prevent progression

Language: Английский

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Glial Perturbation in Metal Neurotoxicity: Implications for Brain Disorders

Neuroglia, Journal Year: 2025, Volume and Issue: 6(1), P. 4 - 4

Published: Jan. 6, 2025

Overexposure of humans to heavy metals and essential poses a significant risk for the development neurological neurodevelopmental disorders. The mechanisms through which these exert their effects include generation reactive oxygen species, mitochondrial dysfunction, activation inflammatory pathways, disruption cellular signaling. function glial cells in brain maintenance homeostasis cannot be overlooked. are particularly susceptible metal-induced neurotoxicity. Accumulation promotes microglial activation, triggering responses that can coincide with other neurotoxicity, inducing alteration synaptic transmission, cognitive deficit, neuronal damage. In this review, we highlighted role dysfunction some selected neurodegenerative diseases We further dive into how exposure such as nickel, manganese, methyl mercury, cadmium, iron, arsenic, lead affect functions microglia, astrocytes, oligodendrocytes they on relation Potential therapeutic interventions use new improved chelating agents antioxidant therapies might approach alleviating perturbations.

Language: Английский

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Patchouli alcohol attenuates the cognitive deficits in a transgenic mouse model of Alzheimer’s disease via modulating neuropathology and gut microbiota through suppressing C/EBPβ/AEP pathway

Journal of Neuroinflammation, Journal Year: 2023, Volume and Issue: 20(1)

Published: Jan. 30, 2023

Abstract Background Alzheimer’s disease (AD) is a chronic neurodegenerative characterized by progressive cognitive dysfunctions and behavioral impairments. Patchouli alcohol (PA), isolated from Pogostemonis Herba , exhibits multiple pharmacological properties, including neuroprotective effects. This study aimed to investigate the therapeutic effects of PA against AD using TgCRND8 transgenic mouse model, explore underlying mechanisms targeting CCAAT/enhancer-binding protein β/asparagine endopeptidase (C/EBPβ/AEP) signaling pathway. Methods After genotyping confirm transgenicity, drug treatments were administered intragastrically once daily 3-month-old mice for 4 consecutive months. Several tests applied assess different aspects neurological functions. Then brain colon tissues harvested in-depth mechanistic studies. To further verify whether exerts anti-AD via modulating C/EBPβ/AEP pathway in mice, adeno-associated virus (AAV) vectors encoding CEBP/β bilaterally injected into hippocampal CA1 region overexpress C/EBPβ. Additionally, fecal microbiota transplantation (FMT) experiment was performed potential role gut on PA. Results Our results showed that treatment significantly improved activities living (ADL), ameliorated anxiety-related deficits impairments mice. modulated amyloid precursor (APP) processing. also markedly reduced levels beta-amyloid (Aβ) 40 Aβ 42 suppressed plaque burdens, inhibited tau hyperphosphorylation at several sites relieved neuroinflammation brains Moreover, restored dysbiosis activation Interestingly, strikingly alleviated AD-like pathologies induced overexpression C/EBPβ FMT PA-treated germ-free Conclusion All these findings amply demonstrated could ameliorate suppressing plaques deposition, protein, through inhibiting pathway, suggesting promising naturally occurring chemical worthy development pharmaceutical AD.

Language: Английский

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The Relationship of Astrocytes and Microglia with Different Stages of Ischemic Stroke

Current Neuropharmacology, Journal Year: 2023, Volume and Issue: 21(12), P. 2465 - 2480

Published: July 19, 2023

Abstract: Ischemic stroke is the predominant cause of severe morbidity and mortality worldwide. Post-stroke neuroinflammation has recently received increasing attention with aim providing a new effective treatment strategy for ischemic stroke. Microglia astrocytes are major components innate immune system central nervous system. They can be involved in all phases stroke, from early stage, contributing to first wave neuronal cell death, late stage involving phagocytosis repair. In vicious cycle exists between activation microglia (through astrocytic connexin 43 hemichannels), aggravating neuroinflammatory injury post-stroke. However, repeatedly activated induce formation glial scars by triggering reactive astrogliosis peri-infarct regions, which may limit movement reverse restrict diffusion inflammation healthy brain tissues, alleviating poststroke. this review, we elucidated various roles summarized their relationship neuroinflammation. We also examined how influence each other at different stages Several potential therapeutic approaches targeting have been reviewed. Understanding details astrocytemicroglia interaction processes will contribute better understanding mechanisms underlying identification interventions.

Language: Английский

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Astrocytic Neuroimmunological Roles Interacting with Microglial Cells in Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1599 - 1599

Published: Jan. 13, 2023

Both astrocytic and microglial functions have been extensively investigated in healthy subjects neurodegenerative diseases. For astrocytes, not only various sub-types were identified but phagocytic activity was also clarified recently is making dramatic progress. In this review paper, we mostly focus on the functional role of astrocytes extracellular matrix interactions between reactive microglia normal states diseases, because authors feel it necessary to elucidate mechanisms among activated glial cells pathology neurological diseases order pave way for drug discovery. Finally, will cyclic phosphatidic acid (cPA), a naturally occurring phospholipid mediator that induces variety biological activities brain both vivo vitro. We propose cPA may serve as novel therapeutic molecule treatment injury neuroinflammation.

Language: Английский

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