Selenium Nanoparticles in Protecting the Brain from Stroke: Possible Signaling and Metabolic Mechanisms

Nanomaterials, Journal Year: 2024, Volume and Issue: 14(2), P. 160 - 160

Published: Jan. 11, 2024

Strokes rank as the second most common cause of mortality and disability in human population across world. Currently, available methods treating or preventing strokes have significant limitations, primarily need to use high doses drugs due presence blood-brain barrier. In last decade, increasing attention has been paid capabilities nanotechnology. However, vast majority research this area is focused on mechanisms anticancer antiviral effects nanoparticles. our opinion, not enough neuroprotective nanomaterials. review, we attempted summarize key molecular brain cell damage during ischemia. We discussed current literature regarding various nanomaterials for treatment strokes. examined features all known nanomaterials, possibility which are currently being studied regard, positive negative properties identified. Particular review was nanoselenium since selenium a vital microelement part very important little-studied proteins, e.g., selenoproteins selenium-containing proteins. An analysis modern studies cytoprotective made it possible establish acute chronic protective aimed combine information action nanoparticles neurodegenerative processes, especially cerebral

Language: Английский

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Aberrant activation of hippocampal astrocytes causes neuroinflammation and cognitive decline in mice

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(7), P. e3002687 - e3002687

Published: July 11, 2024

Reactive astrocytes are associated with neuroinflammation and cognitive decline in diverse neuropathologies; however, the underlying mechanisms unclear. We used optogenetic chemogenetic tools to identify crucial roles of hippocampal CA1 decline. Our results showed that repeated stimulation induced impairment mice decreased synaptic long-term potentiation (LTP), which was accompanied by appearance inflammatory astrocytes. Mechanistic studies conducted using knockout animal models neuronal cultures lipocalin-2 (LCN2), derived from reactive astrocytes, mediated decreasing LTP through reduction NMDA receptors. Sustained provided similar results. Conversely, these phenomena were attenuated a metabolic inhibitor Fiber photometry GCaMP revealed high level astrocyte activation model. findings suggest hippocampus sufficient required induce LCN2 release modulation. This abnormal glial–neuron interaction may contribute pathogenesis disturbances neuroinflammation-associated brain conditions.

Language: Английский

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Lysosomal acidification impairment in astrocyte-mediated neuroinflammation

Journal of Neuroinflammation, Journal Year: 2025, Volume and Issue: 22(1)

Published: March 10, 2025

Abstract Astrocytes are a major cell type in the central nervous system (CNS) that play key role regulating homeostatic functions, responding to injuries, and maintaining blood-brain barrier. also regulate neuronal functions survival by modulating myelination degradation of pathological toxic protein aggregates. have recently been proposed possess both autophagic activity active phagocytic capability which largely depend on sufficiently acidified lysosomes for complete cellular cargos. Defective lysosomal acidification astrocytes impairs their resulting accumulation debris, excessive myelin lipids, aggregates, ultimately contributes propagation neuroinflammation neurodegenerative pathology. Restoration impaired represent new neuroprotective strategy therapeutic direction. In this review, we summarize pathogenic factors, including neuroinflammatory signaling, metabolic stressors, lipid mediated toxicity, contribute impairment associated dysfunction astrocytes. We discuss astrocyte-mediated primarily context diseases along with other brain injuries. then highlight re-acidification as restore well degradative capacity conclude providing future perspectives phagocytes crosstalk CNS cells impart or effects.

Language: Английский

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Polystyrene Nano- and Microplastic Particles Induce an Inflammatory Gene Expression Profile in Rat Neural Stem Cell-Derived Astrocytes In Vitro

Nanomaterials, Journal Year: 2024, Volume and Issue: 14(5), P. 429 - 429

Published: Feb. 27, 2024

Microplastics are considered an emerging environmental pollutant due to their ubiquitous presence in the environment. However, potential impact of microplastics on human health warrants further research. Recent studies have reported neurobehavioral and neurotoxic effects marine rodent models; however, underlying cellular physiology mammals remains unclear. Herein, we exposed neural stem cells cell-derived astrocytes, oligodendrocytes, neurons various sizes concentrations polystyrene nano- microplastics. We investigated uptake, cytotoxicity, alteration gene expression through transcriptome profiling. The cell type most affected by decreased viability were astrocytes after 7 days repeated exposure. Transcriptional analysis showed that 1274 genes differentially expressed 500 nm microplastics, but only 531 altered 50 nanoplastics. Both canonical pathway Kyoto Encyclopedia Genes Genomes upregulated pathways involved neuroinflammation, innate adaptive immunity, migration, proliferation, extracellular matrix remodeling, cytoskeleton structures. downregulated lipid metabolism, specifically fatty acid oxidation cholesterol metabolism. Our results show repeatedly for undergo changes hallmarks astrogliosis.

Language: Английский

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Radial stem astrocytes (aka neural stem cells): Identity, development, physio‐pathology, and therapeutic potential

Acta Physiologica, Journal Year: 2023, Volume and Issue: 238(2)

Published: March 27, 2023

Abstract Adult neurogenesis is a striking example of neuroplasticity, which enables adaptive network remodelling in response to all forms environmental stimulation physiological and pathological contexts. Dysregulation or cessation adult contributes neuropathology negatively affecting brain functions hampering regeneration the nervous tissue while targeting may provide basis for potential therapeutic interventions. Neural stem cells mammalian are at core entry point neurogenesis. By their origin properties, these belong astroglia, represented by radial astrocytes (RSA) exhibit multipotent “stemness”. In neurogenic niches, RSA interact with other cellular components, including protoplasmic astrocytes, turn regulate activity. pathology, become reactive, affects capabilities, whereas reactive parenchymal up‐regulate cell hallmarks able generate progeny that remain within astrocyte lineage. What makes special multipotency, self‐renewing capacity capability types as progeny. A broad understanding features provides an insight into machinery promotes/suppresses neurogenesis, clarifying principles remodelling. this review, we discuss hallmarks, research tools, models subventricular zone along lateral ventricle dentate gyrus hippocampus. We also ageing, has great impact on proliferative RSA, well strategies aimed replacement regeneration.

Language: Английский

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Glial reactivity and T cell infiltration in frontotemporal lobar degeneration with tau pathology

Brain, Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 13, 2023

Abstract Frontotemporal lobar degeneration with tau (FTLD-tau) is a group of tauopathies that underlie ∼50% FTLD cases. Identification genetic risk variants related to innate/adaptive immunity have highlighted role for neuroinflammation and neuroimmune interactions in FTLD. Studies shown microglial astrocyte activation together T cell infiltration the brain THY-Tau22 tauopathy mice. However, this remains be confirmed FTLD-tau patients. We conducted detailed post-mortem study cases including 45 progressive supranuclear palsy clinical frontotemporal dementia, 33 Pick’s disease, 12 FTLD-MAPT 52 control brains characterize link between phosphorylated (pTau) epitopes innate adaptive immunity. Tau pathology was assessed cerebral cortex using antibodies directed against: Tau-2 (phosphorylated unphosphorylated tau), AT8 (pSer202/pThr205), AT100 (pThr212/pSer214), CP13 (pSer202), PHF1 (pSer396/pSer404), pThr181 pSer356. The immunophenotypes microglia astrocytes were phenotypic markers (Iba1, CD68, HLA-DR, CD64, CD32a, CD16 GFAP, EAAT2, glutamine synthetase ALDH1L1 astrocytes). immune response explored via CD4+ CD8+ quantification neuroinflammatory environment investigated expression 30 inflammatory-related proteins V-Plex Meso Scale Discovery. As expected, all pTau increased compared controls. pSer356 greatest versus controls (P< 0.0001), whereas other highest disease. Progressive dementia consistently had lower protein load disease across epitopes. only marker (P = 0.0292) specifically 0.0150). several associations detected microglia, supporting an interplay them. GFAP 0.0345) 0.0019), while unchanged. Markers glutamate cycling function reduced 0.0075; disease: P < 0.0400) implying reactivity associated decreased activity, which further expression. Of inflammatory brain, five chemokines upregulated 0.0400), consistent recruitment 0.0109) 0.0014) cells. note, astrocytic markers. Our results highlight reactivity, remarkably little but involvement form chemokine-driven lymphocytes.

Language: Английский

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Metabolic disorders exacerbate the formation of glial scar after stroke

European Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 59(11), P. 3009 - 3029

Published: April 4, 2024

Metabolic disorders are risk factors for stroke exacerbating subsequent complications. Rapidly after brain injury, a glial scar forms, preventing excessive inflammation and limiting axonal regeneration. Despite the growing interest in wound healing following formation of context metabolic is poorly documented. In this study, we used db/db mice to investigate impact perturbations on repair mechanisms, with focus scarring. First, confirmed development obesity, poor glucose regulation, hyperglycaemia liver steatosis these mice. Then, observed that 3 days 30-min middle cerebral artery occlusion (MCAO), had larger infarct area compared their control counterparts. We next investigated reactive gliosis db/+ demonstrated astrogliosis microgliosis were exacerbated Furthermore, also showed synthesis extracellular matrix (ECM) proteins (i.e., chondroitin sulphate proteoglycan, collagen IV tenascin C) was increased Consequently, first time impair post-stroke increase ECM deposition. Given damage size known influence scar, study now raises question direct hyperglycaemia/obesity glia scar. It paves way promote new therapies targeting improve functional recovery disorders.

Language: Английский

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CCL5 mediated astrocyte-T cell interaction disrupts blood-brain barrier in mice after hemorrhagic stroke

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2023, Volume and Issue: 44(3), P. 367 - 383

Published: Nov. 16, 2023

The crosstalk between reactive astrocytes and infiltrated immune cells plays a critical role in maintaining blood-brain barrier (BBB) integrity. However, how interact with the effect of their interaction on BBB integrity after hemorrhagic stroke are still unclear. By performing RNA sequencing that were activated by interleukin-1α (IL-1α), tumor necrosis factor α (TNFα), complement component 1q (C1q) treatment, we found CCL5 was among top upregulated genes. Immunostaining western blot results demonstrated increased mice brain stroke. Flow cytometry showed knockout astrocytic reduced infiltration CD8+ but not CD4+ T myeloid into (p < 0.05). In addition, tight junction-related proteins ZO-1 Occludin expression; Evans blue leakage, perforin granzyme B improved neurobehavioral outcomes 0.05), while transplantation reversed these protective effects. Moreover, co-culture bEnd.3 induced apoptosis cells, which rescued inhibiting perforin. conclusion, our study suggests mediated represents an important therapeutic target for protecting

Language: Английский

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Exocytosis in Astrocytes

Biomolecules, Journal Year: 2021, Volume and Issue: 11(9), P. 1367 - 1367

Published: Sept. 16, 2021

Until recently, astrocytes were thought to be a part of simple “brain glue” providing only supporting role for neurons. However, the discoveries last two decades have proven dynamic partners participating in brain metabolism and actively influencing communication between The means astrocyte-neuron are diverse, although regulated exocytosis has received most attention but also caused debate. Similar eukaryotic cells, complex range vesicular organelles which can undergo as well intricate molecular mechanisms that regulate this process. In review, we focus on components needed occur summarise knowledge about experimental evidence showing its presence astrocytes.

Language: Английский

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Post-traumatic epilepsy: Insights from human cortical contused tissue

Epilepsy & Behavior, Journal Year: 2025, Volume and Issue: 164, P. 110252 - 110252

Published: Jan. 18, 2025

Language: Английский

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