Role of astroglial toll-like receptors (TLRs) in central nervous system infections, injury and neurodegenerative diseases

Brain Behavior and Immunity, Journal Year: 2020, Volume and Issue: 91, P. 740 - 755

Published: Oct. 8, 2020

Central nervous system (CNS) innate immunity plays essential roles in infections, neurodegenerative diseases, and brain or spinal cord injuries. Astrocytes microglia are the principal cells that mediate CNS. Pattern recognition receptors (PRRs), expressed by astrocytes microglia, sense pathogen-derived endogenous ligands released damaged initiate immune response. Toll-like (TLRs) a well-characterized family of PRRs. The contribution microglial TLR signaling to CNS pathology has been extensively investigated. Even though assume wide variety key functions, information about role astroglial TLRs disease injuries is limited. Because display heterogeneity exhibit phenotypic plasticity depending on effectors present local milieu, they can exert both detrimental beneficial effects. modulators these paradoxical properties. goal current review highlight played diseases. We discuss host defense as well dissemination viral bacterial infections examine link between pathogenesis diseases evidence showing pivotal influence sterile inflammation injury. Finally, we define research questions areas warrant further investigations context astrocytes, TLRs, dysfunction.

Language: Английский

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Traumatic brain injury: Mechanisms, manifestations, and visual sequelae

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

Published: Feb. 23, 2023

Traumatic brain injury (TBI) results when external physical forces impact the head with sufficient intensity to cause damage brain. TBI can be mild, moderate, or severe and may have long-term consequences including visual difficulties, cognitive deficits, headache, pain, sleep disturbances, post-traumatic epilepsy. Disruption of normal functioning leads a cascade effects molecular anatomical changes, persistent neuronal hyperexcitation, neuroinflammation, loss. Destructive processes that occur at cellular level lead inflammation, oxidative stress, calcium dysregulation, apoptosis. Vascular damage, ischemia loss blood barrier integrity contribute destruction tissue. This review focuses on incited during frequently life-altering lasting this vision, cognition, balance, sleep. The wide range complaints associated are addressed repair where there is potential for intervention preservation highlighted.

Language: Английский

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Pathophysiological Responses and Roles of Astrocytes in Traumatic Brain Injury

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(12), P. 6418 - 6418

Published: June 15, 2021

Traumatic brain injury (TBI) is immediate damage caused by a blow to the head resulting from traffic accidents, falls, and sporting activity, which causes death or serious disabilities in survivors. TBI induces multiple secondary injuries, including neuroinflammation, disruption of blood–brain barrier (BBB), edema. Despite these emergent conditions, current therapies for are limited insufficient some cases. Although several candidate drugs exerted beneficial effects animal models, most them failed show significant clinical trials. Multiple studies have suggested that astrocytes play key role pathogenesis TBI. Increased reactive astrocyte-derived factors commonly observed both patients experimental models. Astrocytes detrimental on TBI, promotion restriction neurogenesis synaptogenesis, acceleration suppression repair BBB via bioactive factors. Additionally, astrocytic aquaporin-4 involved formation cytotoxic Thus, attractive targets novel therapeutic although astrocyte-targeting not yet been developed. This article reviews recent observations roles expected

Language: Английский

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HGF and MET: From Brain Development to Neurological Disorders

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: June 9, 2021

Hepatocyte growth factor (HGF) and its tyrosine kinase receptor, encoded by the MET cellular proto-oncogene, are expressed in nervous system from pre-natal development to adult life, where they involved neuronal survival. In this review, we highlight, beyond neurotrophic action, novel roles of HGF-MET synaptogenesis during post-natal brain connection between deregulation expression developmental disorders such as autism spectrum disorder (ASD). On pharmacology side, HGF-induced activation exerts beneficial neuroprotective effects also adulthood, specifically neurodegenerative disease, preclinical models cerebral ischemia, spinal cord injuries, neurological pathologies, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple (MS). HGF is a key preventing death promoting survival through pro-angiogenic, anti-inflammatory, immune-modulatory mechanisms. Recent evidence suggests that acts on neural stem cells enhance neuroregeneration. The possible therapeutic application mimetics for treatment discussed.

Language: Английский

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MiR-17–92 Cluster-Enriched Exosomes Derived from Human Bone Marrow Mesenchymal Stromal Cells Improve Tissue and Functional Recovery in Rats after Traumatic Brain Injury

Journal of Neurotrauma, Journal Year: 2021, Volume and Issue: 38(11), P. 1535 - 1550

Published: March 31, 2021

Exosomes play an important role in intercellular communication by delivering microribonucleic acids (miRNAs) to recipient cells. Previous studies have demonstrated that multi-potent mesenchymal stromal cell (MSC)-derived exosomes improve functional recovery after experimental traumatic brain injury (TBI). This study was performed determine efficacy of miR-17-92 cluster-enriched (Exo-17-92) harvested from human bone marrow MSCs transfected with a cluster plasmid enhancing tissue and neurological compared derived empty vector (Exo-empty) for treatment TBI. Adult male rats underwent unilateral moderate cortical contusion. Animals received single intravenous injection (100 μg/rat, approximately 3.75x1011 particles, Exo-17-92) or control Exo-empty) Vehicle (phosphate-buffered solution) one day injury. A battery tests weekly TBI five weeks. Spatial learning memory were measured on days 31-35 using the Morris water maze test. All animals sacrificed weeks Their brains processed histopathological immunohistochemical analyses lesion volume, loss, angiogenesis, neurogenesis, neuroinflammation. Compared Vehicle, both Exo-17-92 Exo-empty treatments significantly improved sensorimotor cognitive function, reduced neuroinflammation hippocampal neuronal promoted angiogenesis neurogenesis without altering volume. Moreover, exhibited more robust therapeutic effect improvement reducing than did treatment. enriched better improving Exo-empty, likely endogenous neurogenesis. Engineering specific miRNA may provide novel strategy management contusion

Language: Английский

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Microglia and Astrocytes in Amyotrophic Lateral Sclerosis: Disease-Associated States, Pathological Roles, and Therapeutic Potential

Biology, Journal Year: 2023, Volume and Issue: 12(10), P. 1307 - 1307

Published: Oct. 3, 2023

Microglial and astrocytic reactivity is a prominent feature of amyotrophic lateral sclerosis (ALS). Microglia astrocytes have been increasingly appreciated to play pivotal roles in disease pathogenesis. These cells can adopt distinct states characterized by specific molecular profile or function depending on the different contexts development, health, aging, disease. Accumulating evidence from ALS rodent cell models has demonstrated neuroprotective neurotoxic functions microglia astrocytes. In this review, we focused recent advancements knowledge microglial nomenclature, landmark discoveries demonstrating clear contribution pathogenesis, novel therapeutic candidates leveraging these that are currently undergoing clinical trials.

Language: Английский

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Traumatic Brain Injury: A Comprehensive Review of Biomechanics and Molecular Pathophysiology

World Neurosurgery, Journal Year: 2024, Volume and Issue: 185, P. 74 - 88

Published: Jan. 23, 2024

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

Published: May 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.

Language: Английский

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Neuroinflammation and neurodegeneration following traumatic brain injuries

Anatomical Science International, Journal Year: 2024, Volume and Issue: unknown

Published: May 13, 2024

Abstract Traumatic brain injuries (TBI) commonly occur following head trauma. TBI may result in short- and long-term complications which lead to neurodegenerative consequences, including cognitive impairment post-TBI. When investigating the neurodegeneration TBI, studies have highlighted role reactive astrocytes neuroinflammation degeneration process. This review showcases a variety of markers that show astrocyte presence under pathological conditions, glial fibrillary acidic protein (GFAP), Crystallin Alpha-B (CRYA-B), Complement Component 3 (C3) S100A10. Astrocyte activation white-matter inflammation, expressed as hyperintensities. Other changes include increased cortical thickness white matter. addresses gaps literature regarding post-mortem human focussing on astrocytes, alongside potential uses these proteins future investigate proportions post-TBI has been discussed. research benefit focus play assist clinicians managing patients who suffered TBI.

Language: Английский

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Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury

Cells, Journal Year: 2024, Volume and Issue: 13(2), P. 148 - 148

Published: Jan. 12, 2024

Traumatic Brain Injury (TBI) represents a significant health concern, necessitating advanced therapeutic interventions. This detailed review explores the critical roles of astrocytes, key cellular constituents central nervous system (CNS), in both pathophysiology and possible rehabilitation TBI. Following injury, astrocytes exhibit reactive transformations, differentiating into pro-inflammatory (A1) neuroprotective (A2) phenotypes. paper elucidates interactions with neurons, their role neuroinflammation, potential for exploitation. Emphasized strategies encompass utilization endocannabinoid calcium signaling pathways, hormone-based treatments like 17β-estradiol, biological therapies employing anti-HBGB1 monoclonal antibodies, gene therapy targeting Connexin 43, innovative technique astrocyte transplantation as means to repair damaged neural tissues.

Language: Английский

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