Dual roles of astrocytes in plasticity and reconstruction after traumatic brain injury

Cell Communication and Signaling, Journal Year: 2020, Volume and Issue: 18(1)

Published: April 15, 2020

Abstract Traumatic brain injury (TBI) is one of the leading causes fatality and disability worldwide. Despite its high prevalence, effective treatment strategies for TBI are limited. induces structural functional alterations astrocytes, most abundant cell type in brain. As a way coping with trauma, astrocytes respond diverse mechanisms that result reactive astrogliosis. Astrocytes involved physiopathologic an extensive sophisticated manner. Notably, have dual roles TBI, some astrocyte-derived factors double opposite properties. Thus, suppression or promotion astrogliosis does not substantial curative effect. In contrast, selective stimulation beneficial molecules simultaneous attenuation deleterious based on spatiotemporal-environment can provide promising astrocyte-targeting therapeutic strategy. current review, we describe first time specific neuronal plasticity reconstruction, including neurogenesis, synaptogenesis, angiogenesis, repair blood-brain barrier, glial scar formation after TBI. We also classified depending their neuroprotective neurotoxic to design more appropriate targeted therapies.

Language: Английский

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Revisiting Traumatic Brain Injury: From Molecular Mechanisms to Therapeutic Interventions

Biomedicines, Journal Year: 2020, Volume and Issue: 8(10), P. 389 - 389

Published: Sept. 29, 2020

Studying the complex molecular mechanisms involved in traumatic brain injury (TBI) is crucial for developing new therapies TBI. Current treatments TBI are primarily focused on patient stabilization and symptom mitigation. However, field lacks defined to prevent cell death, oxidative stress, inflammatory cascades which lead chronic pathology. Little can be done treat mechanical damage that occurs during primary insult of a TBI; however, secondary mechanisms, such as inflammation, blood-brain barrier (BBB) breakdown, edema formation, excitotoxicity, targeted by therapeutic interventions. Elucidating many underlying studying targets neuroprotective agents critical treatments. Therefore, we present review events following from inflammation programmed death discuss current research latest strategies help understand TBI-mediated injury.

Language: Английский

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Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury

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

Published: June 15, 2020

Abstract Background Aucubin (Au), an iridoid glycoside from natural plants, has antioxidative and anti-inflammatory bioactivities; however, its effects on a traumatic brain injury (TBI) model remain unknown. We explored the potential role of Au in H 2 O -induced oxidant damage primary cortical neurons weight-drop induced-TBI mouse model. Methods In vitro experiments, various concentrations (50 μg/ml, 100 or 200 μg/ml) were added culture medium at 0 h 6 after stimulated by (100 μM). After exposed for 12 h, collected western blot (WB), immunofluorescence, M29,79-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. vivo (20 mg/kg 40 mg/kg) was administrated intraperitoneally 30 min, 24 48 modeling. Brain water content, neurological deficits, cognitive functions measured specific time, respectively. Cortical tissue around focal trauma WB, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, Nissl quantitative real time polymerase chain reaction (q-PCR), immunofluorescence/immunohistochemistry, enzyme linked immunosorbent assay (ELISA) 72 TBI. RNA interference experiments performed to determine nuclear factor erythroid-2 related (Nrf2) TBI mice with (40 treatment. Mice intracerebroventricularly lentivirus before establishment. The cortex obtained used WB q-PCR. Results enhanced translocation Nrf2 into nucleus, activated antioxidant enzymes, suppressed excessive generation reactive oxygen species (ROS), reduced cell apoptosis both experiments. TBI, markedly attenuated edema, histological damages, improved deficits. significantly high mobility group box 1 (HMGB1)-mediated aseptic inflammation. knockdown blunted neuroprotective Au. Conclusions Taken together, our data suggest that provides effect inhibiting oxidative stress inflammatory responses; mechanisms involve triggering Nrf2-induced system.

Language: Английский

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Microglia and Neuroinflammation: Crucial Pathological Mechanisms in Traumatic Brain Injury-Induced Neurodegeneration

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

Published: March 25, 2022

Traumatic brain injury (TBI) is one of the most common diseases in central nervous system (CNS) with high mortality and morbidity. Patients TBI usually suffer many sequelae life time post injury, including neurodegenerative disorders such as Alzheimer’s disease (AD) Parkinson’s (PD). However, pathological mechanisms connecting these two processes have not yet been fully elucidated. It important to further investigate pathophysiological underlying TBI-induced neurodegeneration, which will promote development precise treatment target for notorious consequences after TBI. A growing body evidence shows that neuroinflammation a pivotal process chronic neurodegeneration following Microglia, immune cells CNS, play crucial roles other CNS diseases. Of interest, microglial activation functional alteration has proposed key mediators evolution pathology Here, we review updated studies involving phenotypical alterations microglia survey molecules regulating activities responses pathology, explore their potential implications injury. The work give us comprehensive understanding driving TBI-related offer novel ideas developing corresponding prevention strategies this disease.

Language: Английский

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Traumatic Brain Injury: Mechanisms of Glial Response

Frontiers in Physiology, Journal Year: 2021, Volume and Issue: 12

Published: Oct. 22, 2021

Traumatic brain injury (TBI) is a heterogeneous disorder that involves damage due to external forces. TBI the main factor of death and morbidity in young males with high incidence worldwide. causes central nervous system (CNS) under variety mechanisms, including synaptic dysfunction, protein aggregation, mitochondrial oxidative stress, neuroinflammation. Glial cells comprise most CNS, which are mediators brain’s response TBI. In CNS present astrocytes, microglia, oligodendrocytes, polydendrocytes (NG2 cells). Astrocytes play critical roles ion water homeostasis, energy metabolism, blood-brain barrier, immune response. TBI, astrocytes change their morphology expression. Microglia primary phagocytic activity. After microglia also release both pro anti-inflammatory mediators. Oligodendrocytes myelin producers promoting axonal support. oligodendrocyte apoptosis, demyelination, transport disruption. There various interactions between these glial neurons contribute pathophysiology this review, we summarize several hallmarks relevant for understanding neuronal conditions.

Language: Английский

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Association of Traumatic Brain Injury With the Risk of Developing Chronic Cardiovascular, Endocrine, Neurological, and Psychiatric Disorders

JAMA Network Open, Journal Year: 2022, Volume and Issue: 5(4), P. e229478 - e229478

Published: April 28, 2022

Increased risk of neurological and psychiatric conditions after traumatic brain injury (TBI) is well-defined. However, cardiovascular endocrine comorbidity TBI in individuals without these comorbidities associations with post-TBI mortality have received little attention.To assess the incidence cardiovascular, endocrine, neurological, patients mild (mTBI) or moderate to severe (msTBI) analyze between mortality.This prospective longitudinal cohort study used hospital-based patient registry data from a tertiary academic medical center select any prior clinical who experienced 2000 2015. Using same registry, head injuries, unexposed group, target were selected age-, sex-, race-frequency-matched subgroups. Patients followed-up for up 10 years. Data analyzed 2021.Mild trauma.Cardiovascular, neurologic, defined based on International Classification Diseases, Ninth Revision (ICD-9) Statistical Diseases Related Health Problems, Tenth (ICD-10). Associations comorbidities, as well mortality, analyzed.A total 4351 mTBI (median [IQR] age, 45 [29-57] years), msTBI 47 [30-58] 46 years) included analyses. In each 45% participants women. significantly associated higher risks disorders compared individuals. particular, hypertension was increased both (HR, 2.5; 95% CI, 2.1-2.9) 2.4; 2.0-2.9) groups. Diabetes 1.9; 1.4-2.7) 1.4-2.6) groups, ischemic stroke transient attack also 2.2; 1.4-3.3) 3.6; 2.4-5.3) All subgroups emerged within median (IQR) 3.49 (1.76-5.96) years injury. Risks aged 18 40 age-matched individuals: 5.9; 3.9-9.1) 3.9; 2.5-6.1) while hyperlipidemia 2.3; 1.5-3.4) diabetes 4.6; 2.1-9.9) group. Individuals msTBI, patients, had (432 deaths [9.9%] vs 250 [5.7%]; P < .001); postinjury 1.3; 1.1-1.7), coronary artery disease 1.6-3.0), adrenal insufficiency 6.2; 2.8-13.0) mortality.These findings suggest that severity chronic baseline diagnoses. Medical observed relatively young TBI. Comorbidities occurring mortality. These need targeted screening program multisystem diseases TBI, particularly cardiometabolic diseases.

Language: Английский

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Pathogenesis and management of traumatic brain injury (TBI): role of neuroinflammation and anti-inflammatory drugs

Inflammopharmacology, Journal Year: 2022, Volume and Issue: 30(4), P. 1153 - 1166

Published: July 8, 2022

Abstract Traumatic brain injury (TBI) is an important global health concern that represents a leading cause of death and disability. It occurs due to direct impact or hit on the head caused by factors such as motor vehicles, crushes, assaults. During past decade, abundance new evidence highlighted importance inflammation in secondary damage response contributes neurodegenerative neurological deficits after TBI. results disruption blood–brain barrier (BBB) initiates release macrophages, neutrophils, lymphocytes at site. A growing number researchers have discovered various signalling pathways associated with initiation progression inflammation. Targeting different (NF-κB, JAK/STAT, MAPKs, PI3K/Akt/mTOR, GSK-3, Nrf2, RhoGTPase, TGF-β1, NLRP3) helps development novel anti-inflammatory drugs management Several synthetic herbal both neuroprotective potential showed effective results. This review summarizes pathways, pathologies, inflammatory mediators, pharmacological potential, current status, challenges drugs.

Language: Английский

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Garlic exosome-like nanoparticles reverse high-fat diet induced obesity via the gut/brain axis

Theranostics, Journal Year: 2022, Volume and Issue: 12(3), P. 1220 - 1246

Published: Jan. 1, 2022

Background: Obesity is becoming a global epidemic and reversing the pathological processes underlying obesity metabolic co-morbidities challenging.Obesity induced chronic inflammation including brain hallmark of via gut-brain axis.The objective this study was to develop garlic exosome-like nanoparticles (GaELNs) that inhibit systemic as well inflammatory activity reverse HFD in mice.Methods: GELNs were isolated administrated orally into fed mice.GaELNs fluorescent labeled for monitoring their vivo trafficking route after oral administration quantified number particles several tissues.The determined by measuring cytokines ELISA real-time PCR.Mitochondrial membrane permeability microglial cells using JC-10 fluorescence dye.The apoptotic cell death TUNEL assay.The metabolites identified LC-MS analysis.Memory function mice memory functional analysis.The effect GaELNs on glucose insulin response tolerance tests.c-Myc localization interaction with BASP1 calmodulin confocal microscopy.Results: Our results show preferentially taken up inhibits mice.GaELN phosphatidic acid (PA) (36:4) required uptake BASP1.Formation GaELNs/BASP1 complex inhibition c-Myc mediated expression STING.GaELN PA binds BASP1, leading through competitively binding CaM transcription factor.Inhibition STING leads reducing an array IFN-γ TNF-α.IFN-γ induces IDO1, which turn generated IDO1 dependent manner activate AHR pathway contributes developing obesity.The derived from treated promote neuronal differentiation mitochondrial death.GaELNs showed improved increased sensitivity these mice.Conclusion: Collectively, demonstrate how healthy diet can unhealthy high-fat reveal link between microglia/diet disease outcomes diet-derived nanoparticles.

Language: Английский

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ACT001 attenuates microglia-mediated neuroinflammation after traumatic brain injury via inhibiting AKT/NFκB/NLRP3 pathway

Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 20(1)

Published: April 23, 2022

Abstract Background Microglia-mediated neuroinflammatory response following traumatic brain injury (TBI) is considered as a vital secondary factor, which drives trauma-induced neurodegeneration and lack of efficient treatment. ACT001, sesquiterpene lactone derivative, reportedly involved in alleviation inflammatory response. However, little known regarding its function regulating innate immune central nervous system (CNS) after TBI. This study aimed to investigate the role underlying mechanism ACT001 Methods Controlled cortical impact (CCI) models were used establish model Cresyl violet staining, evans blue extravasation, neurobehavioral assessments, immunofluorescence transmission electron microscopy evaluate therapeutic effects vivo. Microglial depletion was induced by administering mice with colony stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622. Cell-cell interaction established co-culture simulate TBI conditions vitro. Cytotoxic effect on cell viability assessed counting kit-8 activation microglia cells Lipopolysaccharides (LPS). Pro-inflammatory cytokines expression determined Real-time PCR nitric oxide production. Apoptotic detected TUNEL flow cytometry assays. Tube formation performed cellular angiogenic ability. ELISA western blot experiments determine proteins expression. Pull-down assay analyze that bound ACT001. Results relieved extent blood-brain barrier integrity damage alleviated motor deficits via reducing cells. Delayed PLX5622 hindered Furthermore, LPS-induced mouse rat primary Besides, effective suppressing pro-inflammatory production BV2 cells, resulting reduction neuronal apoptosis HT22 improvement tube bEnd.3 Mechanism functioned related AKT/NFκB/NLRP3 pathway. restrained NFκB nuclear translocation through inhibiting AKT phosphorylation, decrease NLRP3 inflammasome activation, finally down-regulated microglial Conclusions Our indicated played critical microglia-mediated might be novel potential chemotherapeutic drug for

Language: Английский

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Microglia activation in central nervous system disorders: A review of recent mechanistic investigations and development efforts

Frontiers in Neurology, Journal Year: 2023, Volume and Issue: 14

Published: March 7, 2023

Microglia are the principal resident immune cells in central nervous system (CNS) and play important roles development of CNS disorders. In recent years, there have been significant developments our understanding microglia, we now greater insight into temporal spatial patterns microglia activation a variety disorders, as well interactions between neurons. A signaling pathways implicated. However, to date, all published clinical trials failed demonstrate efficacy over placebo. This review summarizes results studies attempts provide mechanistic view activation, inflammation, tissue repair,

Language: Английский

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