Inflammation From Peripheral Organs to the Brain: How Does Systemic Inflammation Cause Neuroinflammation?

Frontiers in Aging Neuroscience, Journal Year: 2022, Volume and Issue: 14

Published: June 16, 2022

As inflammation in the brain contributes to several neurological and psychiatric diseases, cause of neuroinflammation is being widely studied. The causes can be roughly divided into following domains: viral infection, autoimmune disease, from peripheral organs, mental stress, metabolic disorders, lifestyle. In particular, effects caused by organs have yet unclear mechanisms. Many such as gastrointestinal inflammation, chronic obstructive pulmonary rheumatoid arthritis, dermatitis, fatigue syndrome, or myalgic encephalomyelitis (CFS/ME), trigger through pathways. mechanisms action for inflammation-induced include disruption blood-brain barrier, activation glial cells associated with systemic immune activation, on autonomic nerves via organ-brain axis. this review, we consider previous studies relationship between neuroinflammation, focusing regions susceptible inflammation.

Language: Английский

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Neuroinflammation, memory, and depression: new approaches to hippocampal neurogenesis

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

Published: Nov. 27, 2023

As one of most common and severe mental disorders, major depressive disorder (MDD) significantly increases the risks premature death other medical conditions for patients. Neuroinflammation is abnormal immune response in brain, its correlation with MDD receiving increasing attention. has been reported to be involved through distinct neurobiological mechanisms, among which dysregulation neurogenesis dentate gyrus (DG) hippocampus (HPC) The DG two niches adult mammalian neurotrophic factors are fundamental regulators this process. cell types mediating neuroinflammation include microglia, astrocytes, oligodendrocytes, meningeal leukocytes, peripheral cells selectively penetrate blood-brain barrier infiltrate into inflammatory regions. This review summarizes functions affected by during progression corresponding influences on memory patients model animals.

Language: Английский

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Exercise mimetics: a novel strategy to combat neuroinflammation and Alzheimer’s disease

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Feb. 2, 2024

Abstract Neuroinflammation is a pathological hallmark of Alzheimer’s disease (AD), characterized by the stimulation resident immune cells brain and penetration peripheral cells. These inflammatory processes facilitate deposition amyloid-beta (Aβ) plaques abnormal hyperphosphorylation tau protein. Managing neuroinflammation to restore homeostasis decrease neuronal damage therapeutic approach for AD. One way achieve this through exercise, which can improve function protect against neuroinflammation, oxidative stress, synaptic dysfunction in AD models. The neuroprotective impact exercise regulated various molecular factors that be activated same as administration their mimetics. Recent evidence has proven some mimetics effective alleviating AD, and, additionally, they are helpful alternative option patients who unable perform regular physical manage neurodegenerative disorders. This review focuses on current state knowledge mimetics, including efficacy, regulatory mechanisms, progress, challenges, limitations, future guidance application therapy.

Language: Английский

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BDNF reverses aging-related microglial activation

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

Published: July 14, 2020

Abstract Background Excessive microglial activation is implicated in the pathogenesis of various age-related neurodegenerative diseases. In addition to neurons, brain-derived neurotrophic factor (BDNF) and its receptor TrkB are also expressed microglia. However, direct effect BDNF on has rarely been investigated. Methods We began address this question by examining age BDNF-TrkB pathway mice. By using pharmacological genetic approaches, roles downstream signaling pathways related neurotoxicity were examined cell line primary cells. Results showed that was evident brains aged The levels microglia decreased with negatively correlated their statuses mice during aging. Interestingly, aging-related could be reversed chronic, subcutaneous perfusion BDNF. Peripheral lipopolysaccharide (LPS) injection-induced reduced local supplement BDNF, while shTrkB induced naïve cultured cells, inhibited LPS-induced activation, including morphological changes, activations p38, JNK, NF-кB, productions proinflammatory cytokines. These effects blocked shTrkB. ErK CREB which then competed NF-кB for binding a common coactivator, CREB-binding protein. Conclusions Decreasing aging favors upregulation inhibits via TrkB-Erk-CREB pathway.

Language: Английский

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The emerging role of the BDNF-TrkB signaling pathway in the modulation of pain perception

Journal of Neuroimmunology, Journal Year: 2020, Volume and Issue: 349, P. 577406 - 577406

Published: Sept. 25, 2020

Language: Английский

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Recent Advances in Cell-Based Therapies for Ischemic Stroke

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(18), P. 6718 - 6718

Published: Sept. 14, 2020

Stroke is the most prevalent cardiovascular disease worldwide, and still one of leading causes death disability. Stem cell-based therapy actively being investigated as a new potential treatment for certain neurological disorders, including stroke. Various types cells, bone marrow mononuclear mesenchymal stem dental pulp neural inducible pluripotent genetically modified cells have been found to improve outcomes in animal models stroke, there are some ongoing clinical trials assessing their efficacy humans. In this review, we aim summarize recent advances therapies treat

Language: Английский

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Sestrin2 overexpression attenuates osteoarthritis pain via induction of AMPK/PGC-1α-mediated mitochondrial biogenesis and suppression of neuroinflammation

Brain Behavior and Immunity, Journal Year: 2022, Volume and Issue: 102, P. 53 - 70

Published: Feb. 10, 2022

Language: Английский

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Extracellular vesicles derived from mesenchymal stem cells alleviate neuroinflammation and mechanical allodynia in interstitial cystitis rats by inhibiting NLRP3 inflammasome activation

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: April 6, 2022

Neuroinflammation in spinal dorsal horn (SDH) plays an important role the pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS). Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) exert potent anti-inflammatory activities treatment various diseases. This study aimed to determine therapeutic effects MSC-EVs on IC and furtherly investigate potential mechanism attenuate neuroinflammation.Female rat model was established by intraperitoneal injection cyclophosphamide (50 mg/kg, every 3 days for doses). Inhibition NLRP3 inflammasome performed MCC950 (10 mg/kg). were isolated from culture supernatants human umbilical cord derived MSCs using ultracentrifugation, then injected intrathecally into rats (20 μg 10 μl PBS, other day Suprapubic mechanical allodynia assessed up-down method with von Frey filaments, micturition frequency examined urodynamics. The expression components (NLRP3 Caspase-1), glial cell markers (IBA-1 GFAP), proinflammatory cytokines (TNF-α, IL-1β, IL-6 IL-18) TLR4/NF-κB signal pathway (TLR4, p65 NK-κB phospho-p65 NK-κB) L6-S1 SDH measured Western blot analysis. cellular localization detected immunofluorescence co-staining.NLRP3 activated neurons rats. activation contributed cells process neuroinflammation rats, related suprapubic frequent micturition. Intrathecal alleviated restrained attenuated SDH. In addition, MSC-EV significantly inhibited both inflammasomes pathway.NLRP3 is involved IC. alleviates inhibiting inflammasome, may be regulatory target.

Language: Английский

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BDNF Therapeutic Mechanisms in Neuropsychiatric Disorders

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(15), P. 8417 - 8417

Published: July 29, 2022

Brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin in adult brain and functions as both a primary signal neuromodulator. It serves essential roles neuronal development, maintenance, transmission, plasticity, thereby influencing aging, cognition, behavior. Accumulating evidence associates reduced central peripheral BDNF levels with various neuropsychiatric disorders, supporting its potential utilization biomarker of pathologies. Subsequently, extensive research has been conducted to evaluate restoring, or otherwise augmenting, transmission therapeutic approach. Promising results were indeed observed for genetic upregulation exogenous administration using multitude murine models neurological psychiatric diseases. However, varying mechanisms have proposed underlie effects, many findings indicate engagement disease-specific other non-specific mechanisms. This because essentially affects all aspects cellular function through tropomyosin receptor kinase B (TrkB) signaling, disruptions which vary between regions across different pathologies leading diversified consequences on cognition Herein, we review neurophysiology signaling classify converging diverging molecular underlying potentials disorders. These include neuroprotection, synaptic immunomodulation, plasticity facilitation, secondary neuromodulation, preservation neurovascular unit integrity viability. Lastly, discuss several suggesting common mediator actions centrally acting pharmacological agents used treatment illness.

Language: Английский

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Brain-derived neurotrophic factor (BDNF) has direct anti-inflammatory effects on microglia

Frontiers in Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: June 19, 2023

Microglia are the primary immunocompetent cells that protect brain from environmental stressors, but can also be driven to release pro-inflammatory cytokines and induce a cytotoxic environment. Brain-derived neurotrophic factor (BDNF) is important for regulation of plasticity, synapse formation, general neuronal health. Yet, little known about how BDNF impacts microglial activity. We hypothesized would have direct modulatory effect on cortical (Postnatal Day 1-3: P1-3) microglia (Embryonic 16: E16) cultures in context bacterial endotoxin. To this end, we found treatment following LPS-induced inflammation had marked anti-inflammatory effect, reversing both IL-6 TNF-α microglia. This was transferrable neurons, such LPS-activated media able produce an inflammatory when added separate culture, again, priming attenuated effect. reversed overall impact LPS exposure speculate directly play role regulating state hence, influence microglia-neuron interactions.

Language: Английский

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