Role of CD93 in Health and Disease

Cells, Journal Year: 2023, Volume and Issue: 12(13), P. 1778 - 1778

Published: July 4, 2023

CD93 (also known as complement protein 1 q subcomponent receptor C1qR1 or C1qRp), is a transmembrane glycoprotein encoded by gene located on 20p11.21 and composed of 652 amino acids. can be present in two forms: soluble (sCD93) membrane-bound (CD93). mainly expressed endothelial cells, where it plays key role promoting angiogenesis both physiology disease, such age-related macular degeneration tumor angiogenesis. In fact, highly tumor-associated vessels its presence correlates with poor prognosis, immunotherapy response, immune cell infiltration high tumor, node metastasis (TNM) stage many cancer types. also hematopoietic stem cytotrophoblast platelets i.e., monocytes, neutrophils, B cells natural killer (NK) cells. Accordingly, involved modulating important inflammatory-associated diseases including systemic sclerosis neuroinflammation. Finally, cardiovascular disease development progression. this article, we reviewed the current literature regarding angiogenesis, inflammation growth order to understand could potential therapeutic target modify outcome abovementioned pathologies.

Language: Английский

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Reactive gliosis in traumatic brain injury: a comprehensive review

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Feb. 28, 2024

Traumatic brain injury (TBI) is one of the most common pathological conditions impacting central nervous system (CNS). A neurological deficit associated with TBI results from a complex pathogenetic mechanisms including glutamate excitotoxicity, inflammation, demyelination, programmed cell death, or development edema. The critical components contributing to CNS response, damage control, and regeneration after are glial cells–in reaction tissue damage, their activation, hypertrophy, proliferation occur, followed by formation scar. scar creates barrier in damaged helps protect acute phase post-injury. However, this process prevents complete recovery late/chronic producing permanent scarring, which significantly impacts function. Various types participate formation, but mostly attributed reactive astrocytes microglia, play important roles several pathologies. Novel technologies whole-genome transcriptomic epigenomic analyses, unbiased proteomics, show that both microglia represent groups heterogenic subpopulations different genomic functional characteristics, responsible for role neurodegeneration, neuroprotection regeneration. Depending on representation distinct glia subpopulations, as well regenerative processes delayed neurodegeneration may thus differ nearby remote areas structures. This review summarizes process, where resultant effect severity-, region- time-dependent determined model distance explored area lesion site. Here, we also discuss findings concerning intercellular signaling, long-term possibilities novel therapeutical approaches. We believe comprehensive study an emphasis cells, involved post-injury processes, be helpful further research decisive factor when choosing model.

Language: Английский

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Immune Response in Traumatic Brain Injury

Current Neurology and Neuroscience Reports, Journal Year: 2024, Volume and Issue: 24(12), P. 593 - 609

Published: Oct. 29, 2024

Abstract Purpose of Review This review aims to comprehensively examine the immune response following traumatic brain injury (TBI) and how its disruption can impact healing recovery. Recent Findings The is now considered a key element in pathophysiology TBI, with consequences far beyond acute phase after injury. A delicate equilibrium crucial for healthy When this disrupted, chronic inflammation imbalance lead detrimental effects on survival disability. Summary Globally, imposes substantial burden terms both years life lost lived Although epidemiology exhibits dynamic trends over time across regions, TBI disproportionally affects younger populations, posing psychosocial financial challenge communities families. Following initial trauma, primary succeeded by an inflammatory response, primarily orchestrated innate system. inflammasome plays pivotal role during stage, catalyzing programmed cell death pathways up-regulation cytokines transcription factors. These events trigger activation differentiation microglia, thereby intensifying systemic level facilitating migration cells edema. initially originated brain, monitored our autonomic nervous Through vagus nerve adrenergic cholinergic receptors various peripheral lymphoid organs cells, bidirectional communication regulation between systems established.

Language: Английский

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Increased inflammasome protein expression identified in microglia from postmortem brains with schizophrenia

Journal of Neuropathology & Experimental Neurology, Journal Year: 2024, Volume and Issue: 83(11), P. 951 - 966

Published: June 21, 2024

Abstract Schizophrenia (SCZ) is a complex psychiatric disorder that involves an inflammatory response thought to be characterized by microglial activation. The inflammasome may play critical roles in the pathomechanism of neuroinflammation but how this relates SCZ remains unclear. In study, we performed immunohistochemical (IHC) analysis compare expression proteins brain tissue from donors with (n = 16) and non-psychiatric (NP; n 13) isolated superior frontal cortex (SFC), temporal cortex, anterior cingulate regions. To assess changes cell populations express key proteins, IHC analyses apoptosis-associated speck-like protein containing CARD (ASC), nod-like receptor 3 (NLRP3), interleukin (IL)-18 determine if these are expressed microglia, astrocytes, oligodendrocytes, or neurons. Inflammasome were mainly microglia NP brains. Increased numbers present SFC brains exhibited higher ASC, NLRP3, IL-18 compared NPs. These findings suggest increased signaling contribute pathology underlying SCZ.

Language: Английский

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Sex Differences in the Inflammatory Profile in the Brain of Young and Aged Mice

Cells, Journal Year: 2023, Volume and Issue: 12(10), P. 1372 - 1372

Published: May 12, 2023

Neurodegenerative diseases are a leading cause of death worldwide with no cures identified. Thus, there is critical need for preventative measures and treatments as the number patients expected to increase. Many neurodegenerative have sex-biased prevalence, indicating examine sex differences when investigating prevention treatment strategies. Inflammation key contributor many promising target since inflammation increases age, which known inflammaging. Here, we analyzed protein expression levels cytokines, chemokines, inflammasome signaling proteins in cortex young aged male female mice. Our results show an increase caspase-1, interleukin (IL)-1β, apoptosis-associated speck-like containing caspase recruitment domain (ASC), ASC specks females compared males. Additionally, was IL-1α, VEGF-A, CCL3, CXCL1, CCL4, CCL17, CCL22 aging IL-8, IL-17a, IL-7, LT-α, IL-12/IL-23p40, CCL13, IL-10 were increased males but not age. These indicate that cortical inflammaging provide potential targets attenuate prevent development disease.

Language: Английский

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The neuroprotective potential of phytochemicals in traumatic brain injury: mechanistic insights and pharmacological implications

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 4, 2024

Traumatic brain injury (TBI) leads to damage, comprising both immediate primary damage and a subsequent cascade of secondary mechanisms. The results in localized while the initiates inflammatory responses, followed by disruption blood-brain barrier, infiltration peripheral blood cells, edema, release various immune mediators, including chemotactic factors interleukins. TBI disrupts molecular signaling, cell structures, functions. In addition physical tissue such as axonal injuries, contusions, haemorrhages, interferes with functioning, impacting cognition, decision-making, memory, attention, speech capabilities. Despite deep understanding pathophysiology TBI, an intensive effort evaluate underlying mechanisms effective therapeutic interventions is imperative manage repercussions TBI. Studies have commenced explore potential employing natural compounds for These are characterized their low toxicity limited interactions conventional drugs. Moreover, many demonstrate capacity target aspects process. While our there urgent need mitigate its consequences. Here, we aimed summarize mechanism action role phytochemicals against progression. This review discusses implications phytonutrients addresses consequences addition, highlighted roles emerging promising candidates intervention highlights neuroprotective mechanistic approach. Furthermore, efforts focused on mechanisms, providing better therapeutics.

Language: Английский

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Beneficial Effects of Human Schwann Cell-Derived Exosomes in Mitigating Secondary Damage After Penetrating Ballistic-Like Brain Injury

Journal of Neurotrauma, Journal Year: 2024, Volume and Issue: 41(21-22), P. 2395 - 2412

Published: March 6, 2024

There is a growing body of evidence that the delivery cell-derived exosomes normally involved in intracellular communication can reduce secondary injury mechanisms after brain and spinal cord improve outcomes. Exosomes are nanometer-sized vesicles released by Schwann cells may have neuroprotective effects reducing posttraumatic inflammatory processes as well promoting tissue healing functional recovery. The purpose this study was to evaluate beneficial human Schwann-cell (hSC-Exos) severe model penetrating ballistic-like (PBBI) rats investigate on multiple Human cell processing protocols followed Current Good Manufacturing Practices (cGMP) with exosome extraction purification steps approved FDA for an expanded access single ALS patient IND. Anesthetized male Sprague-Dawley (280-350g) underwent PBBI surgery or sham procedures starting 30 min received either dose hSC-Exos PBS through jugular vein. At 48hrs PBBI, flow cytometry analysis cortical revealed administration reduced number activated microglia levels caspase-1, marker inflammasome activation. Neuropathological at 21 days showed treatment significantly overall contusion volume decreased frequency Iba-1 positive amoeboid immunocytochemical analysis. This systemic TBI reduces histopathological damage. represents clinically relevant cell-based therapy limit detrimental neurotrauma other progressive neurological injuries impacting pathophysiological events

Language: Английский

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Extracellular vesicles mediate inflammasome signaling in the brain and heart of Alzheimer’s disease mice

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: April 10, 2024

Introduction Alzheimer’s disease (AD) is an inflammatory neurodegenerative characterized by memory loss and cognitive impairment that worsens over time. AD associated with many comorbidities, including cardiovascular are poorer outcomes. Comorbidities, especially heart stroke, play a significant role in the demise of patients. Thus, it important to understand how comorbidities linked AD. We have previously shown extracellular vesicle (EV)-mediated inflammasome signaling plays pathogenesis brain injury acute lung after traumatic injury. Methods analyzed cortical, hippocampal, ventricular, atrial protein lysates from APP/PS1 mice their respective controls for activation. Additionally, we serum-derived EV size, concentration, content proteins as well marker CD63. Finally, performed conditioned media experiments patients healthy age-matched delivered cells culture assess EV-induced inflammation. Results show increase Pyrin, NLRP1, caspase-1, ASC cortex whereas caspase-8, ASC, IL-1β were significantly elevated ventricles when compared controls. did not find differences size or concentration between groups, but there was caspase-1 In addition, resulted activation, increases TNF-α IL-2. Conclusion These results indicate EV-mediated may development diseases

Language: Английский

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Genetic predisposition to Alzheimer's disease alters inflammasome activity after traumatic brain injury

Translational research, Journal Year: 2023, Volume and Issue: 257, P. 66 - 77

Published: Feb. 8, 2023

Traumatic Brain Injury (TBI) is a major cause of death and disability in the US recognized risk factor for development Alzheimer's disease (AD). The relationship between these conditions not completely understood, but may share additive or synergistic pathological hallmarks that serve as novel therapeutic targets. Heightened inflammasome signaling plays critical role pathogenesis central nervous system injury (CNS) release apoptosis-associated speck-like protein containing caspase recruitment domain (ASC) speck from neurons activated microglia contribute significantly to TBI AD pathology. This study investigated whether after was augmented this pathway impacted biochemical neuropathological outcomes overall cognitive function. Five-month-old, 3xTg mice respective wild type controls were randomized underwent moderate controlled cortical impact (CCI) served sham/uninjured controls. Animals sacrificed at 1 hour, day, week assess acute pathology 12 weeks assessing ipsilateral cerebral cortex processed expression by immunoblotting. Mice evaluated behavior open field (3 days), object recognition (2 weeks), Morris water maze (6 weeks) testing TBI. There statistically significant increase proteins Caspase-1, Caspase-8, ASC, interleukin (IL)-1β both animals. At 1-day post injury, increases ASC IL-1β measured compared WT Behavioral showed injured had altered function when mice. Elevated Aβ seen hippocampus sham groups injury. Moreover, treatment with IC100, an anti-ASC monoclonal antibody, inhibited inflammasome, evidenced reduction 1-week These findings show response heightened genetically predisposed suggests exacerbate Thus, dampening offer approach

Language: Английский

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Age-Related Alterations in Immune Function and Inflammation: Focus on Ischemic Stroke

Aging and Disease, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 1, 2023

The aging of the global population poses significant scientific challenges. Moreover, biological process is most risk factor for chronic illnesses; therefore, understanding molecular and cellular mechanisms underlying these aging-related challenges crucial extending healthy lifespan older individuals. Preventing brain remains a priority public health goal, integrative comprehensive analyses have revealed that immunosenescence potential cause age-related damage disease (e.g., stroke). Importantly, neuroinflammatory immune systems present two-way contact thus can affect each other. Emerging evidence supports numerous effects immunosenescence- inflammation-mediated immunity in neurologically injured brains. In this study, we briefly outline how alters pathophysiology transcriptional amplitude patients who experienced stroke then discuss system its components are affected by age after stroke. Finally, highlight emerging interventions with to slow down or reduce prevent onset.

Language: Английский

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