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Palmitic acid-induced autolysosomal dysfunction and lipotoxicity in neuroinflammation and neurodegeneration.

Neurodegenerative disorders such as Alzheimer's and Parkinson's diseases are increasingly associated with metabolic dysfunction, including o … y susceptible to lipid-induced toxicity due to their high metabolic demands. Glial cells, including astrocytes, microglia, and oligodendrocytes, also exhibit distinct vulnerabilities and adaptive responses to lipid metabolism dysregulation, further contributing to neuroinflammation and demyelination. Therapeutic strategies, such as supplementation with polyu …

Pten Loss Triggers Progressive Photoreceptor Degeneration in an mTORC1-Independent Manner.

PURPOSE: Silencing Phosphatase and tensin homolog (Pten) is a proposed therapeutic strategy for tissue regeneration to treat neurological di … changes in photoreceptor gene expression and used immunostaining to assess photoreceptors, reactive astrocytes, microglia, angiogenesis, and subretinal deposit formation from postnatal day (P) 21 to 1 year of age. Pten RPC-cKO retinal explants were treated with rapamycin, an mTOR inhibitor, or 2-deoxy-D-glucose (2DG), a glycolysis inhibitor. RESULTS: In bot …

The therapeutic potential of neuroglobin-overexpressing human neural stem cells in a photothrombosis model.

BACKGROUND: Neuroglobin (NGB) is an oxygen-binding protein with neuroprotective properties under hypoxic and ischemic conditions. It promote … ining confirmed that F3.NGB cells migrated to the infarcted region, differentiated into neurons and astrocytes, and showed strong Ki67 positivity, indicating active proliferation at the injury site. CONCLUSION: These findings demonstrate that F3.NGB cells reduce ischemic brain damage primarily by enhancing cell proliferation, and also migrate to the injury …

The Role of Hydrogen Sulfide in the Localization and Structural-Functional Organization of p53 Following Traumatic Brain Injury: Development of a YOLO Model for Detection and Quantification of Apoptotic Nuclei.

Traumatic brain injury (TBI) triggers a cascade of molecular and cellular disturbances, including apoptosis, inflammation, and destabilization of neuronal connections. The transcription factor p53 plays a pivotal role in regulating cell fate following brain injury by initiating pro-apoptotic signaling cascades. Hydrogen sulfide (H2S) may significantly contribute to the regulation of p53. Using scanning laser confocal microscopy, we found that after TBI, p53 accumulates extensively in the damaged cerebral cortex, showing distinct subcellular localization in neurons and astrocytes. In neurons, p…

Development and in vitro evaluation of biomimetic injectable hydrogels from decellularized human nerves for central nervous system regeneration.

Injuries to the central nervous system (CNS) often lead to persistent inflammation and limited regeneration. This study developed a clinical … hat gelled within 12 min at 37 °C and exhibited mechanical stiffness of approximately 400 Pa. Human astrocytes, human microglial cell clone 3 (HMC3), and mouse RAW 264.7 macrophages were cultured individually within iHPN, with lipopolysaccharide (LPS) added to mimic CNS inflammation following injury. Compared to LPS-activated cells on tissue culture plates ( …

CVA16 infection causes neurological injury by engaging TLR2/MYD88/TNF-α/CXCL1 signalling pathway in hSCARB2 knock-in mice.

Coxsackievirus A16 (CVA16), a major pathogen responsible for hand-foot-and-mouth disease (HFMD) in children, has frequently replaced Enterov … nofluorescence staining revealed extensive inflammation, marked by the concentrated infiltration of astrocytes cells, as well as severe neurological injury, which included hypertrophic and extended pseudopodia microglia, increased astrocytes with long and stretched protuberances, markedly decreased neuronal cell bodies and nerve fibers in brain. No visible p …

Нейроинфламматизирующие организмы мозга человека позволяют проводить комплексные исследования по скринингу наркотиков: Fingolimod и его аналоги в фокусе.

ВВЕДЕНИЕ: Отсутствие физиологически значимых моделей нервно-воспалительных расстройств мозга, таких, как множественный склероз (MS), подчеркивает необходимость совершенствования платформ скрининга лекарств. Для преодоления этого разрыва цель этого исследования состояла в разработке модели человеческого мозгового органоида (HBO), включающей в себя основные типы нейронных клеток, включая астроциты, микроглию и олигодендроциты. МЕТОДЫ: hBO были получены из стволовых клеток H9, а нейро-воспалительные характеристики были получены липополизакхаридом (LPS). Определение конкретных нейронных и подстрек

Совпадение в аннотации оригинала
INTRODUCTION: The absence of physiologically relevant models for neuroinflammatory brain disorders, such as multiple sclerosis (MS), highlights the need for improved drug screening platforms. To bridge this gap, this study aimed to develop a human brain organoid (hBO) model incorporating essential neural cell types, including astrocytes, microglia, and oligo…

Астроглиальная модуляция синаптической функции в недемилинированной коре головного мозга зависит от сигнала MyD88 в модели токсичного обезвоживания.

Прогрессивный неврологический спад в множественном склерозе связан с аксонной потерей и синаптической дисфункцией в недемилинированном нормальном сером веществе (NAGM) и занимает видное место в мозжечке. В отличие от ранних стадий заболеваний, когда синаптическая и нейро-аксональная патология коррелирует с масштабами инфильтрации клеток Т, для прогрессивных MS была предложена важная роль врожденной иммунной системы. Вместе с тем конкретный вклад микроглии и астроцитов в синаптическую патологию мозгового мозга в НГММ - независимо от адаптивной реакции Т клеток - по-прежнему в значительной степе

Совпадение в аннотации оригинала
Progressive neurological decline in multiple sclerosis is associated with axonal loss and synaptic dysfunction in the non-demyelinated norma … ne system has been proposed for progressive MS. However, the specific contribution of microglia and astrocytes to synaptic cerebellar pathology in the NAGM- independent of an adaptive T cell response - remains largely unexplored. In the present study, we quantified synaptic changes in the cerebellar NAGM distant from demyelinated lesions in a mouse model of …

Роль CD20+T клеток в раннем множественном склерозе.

Релапсирующий множественный склероз (RRMS) — хроническое иммунное заболевание центральной нервной системы (CNS), характеризующееся эпизодическими рецидивами неврологических симптомов. Ранняя диагностика и лечение пациентов имеют ключевое значение для предотвращения рецидивов и необратимого ущерба для ЦНС. Вместе с тем развитие методов лечения, ориентированных на ранние МЗ, сдерживается отсутствием знаний о патогенезе ранней МЗ. В RRMS повреждение нервной ткани вызывается иммунными клетками CNS, в том числе Т. Таким образом, цель этого исследования заключалась в изучении ранних случаев инфильтр

Совпадение в аннотации оригинала
Relapsing-remitting multiple sclerosis (RRMS) is a chronic immune-mediated disease of the central nervous system (CNS) characterized by epis … vestigate the early events of CNS infiltration by T cells in RRMS, including their interaction with astrocytes and brain endothelial cells. Using a human in vitro model system and tissue samples obtained from newly diagnosed patients and healthy individuals, we found that CD8+CD20+ T cells could cross the blood-brain-barrier (BBB) and blood-cerebrospinal flu …

The Janus face of antipsychotics in glial cells: Focus on glioprotection.

Antipsychotics are commonly prescribed to treat several neuropsychiatric disorders, including schizophrenia, mania in bipolar disorder, auti … neuropsychiatric disorders, as well as targets to improve the efficacy of these drugs. Glial cells (astrocytes, oligodendrocytes, and microglia) are critical for the central nervous system in both physiological and pathological conditions. Astrocytes are the most abundant glial cells and play important roles in brain homeostasis, regulating neurotransmitter …

Interplay between Energy Supply and Glutamate Toxicity in the Primary Cortical Culture.

Limited substrate availability because of the blood-brain barrier (BBB) has made the brain develop specific molecular mechanisms to survive, using lactate synthesized by astrocytes as a source of energy in neurons. To understand if lactate improves cellular viability and susceptibility to glutamate toxicity, primary cortical cells were incubated in glucose- or lactate-containing media and toxic concentrations of glutamate for 24 h. Cell death was determined by immunostaining and lactate dehydrogenase (LDH) release. Mitochondrial membrane potential and nitric oxide (NO) levels were measured usi…

The enigma of depression in corticobasal degeneration, a frequent but poorly understood co-morbidity.

Depression is one of the most frequent neuropsychiatric symptoms in corticobasal degeneration (CBD), a rare, sporadic, and late-onset progre … cortex and striatum, widespread thread-like structures, pathognomonic "astroglial plaques", "tufted astrocytes", and numerous "coiled bodies" (in astrocytes and oligodendroglia) in cerebral white matter. CBD is non-specific, as pathologically proven cases include several clinical phenotypes. Pubmed and Google Scholar were systematically analyzed until Octobe …

Intrinsic ecto-5'-Nucleotidase/A1R Coupling may Confer Neuroprotection to the Cerebellum in Experimental Autoimmune Encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is widely used animal model of multiple sclerosis (MS). The disease is characterized by demyelination and neurodegeneration triggered by infiltrated autoimmune cells and their interaction with astrocytes and microglia. While neuroinflammation is most common in the spinal cord and brainstem, it is less prevalent in the cerebellum, where it predisposes to rapid disease progression. Because the induction and progression of EAE are tightly regulated by adenosinergic signaling, in the present study we compared the adenosine-producing and -degrading en…

IL-6 deficiency accelerates cerebral cryptococcosis and alters glial cell responses.

Cryptococcus neoformans (Cn) is an opportunistic encapsulated fungal pathogen that causes life-threatening meningoencephalitis in immunosuppressed individuals. Since IL-6 is important for blood-brain barrier support and its deficiency has been shown to facilitate Cn brain invasion, we investigated the impact of IL-6 on systemic Cn infection in vivo, focusing on central nervous system (CNS) colonization and glial responses, specifically microglia and astrocytes. IL-6 knock-out (IL-6-/-) mice showed faster mortality than C57BL/6 (Wild-type) and IL-6-/- supplemented with recombinant IL-6 (rIL-6; …

Microglia activation and neuronal alterations in retinas from COVID-19 patients: correlation with clinical parameters.

BACKGROUND: Different ocular alterations have been described in patients with coronavirus disease 2019 (COVID-19). Our aim was to determine whether COVID-19 affected retinal cells and establish correlations with clinical parameters. METHODS: Retinal sections and flat-mount retinas from human donors with COVID-19 (n = 16) and controls (n = 15) were immunostained. The location of angiotensin-converting enzyme 2 (ACE2) and the morphology of microglial cells, Müller cells, astrocytes, and photoreceptors were analyzed by confocal microscopy. Microglial quantification and the area occupied by them …

Establishment of a minimally invasive distal traumatic optic neuropathy model in mice to investigate cascade reactions of retinal glial cells.

Traumatic optic neuropathy (TON) is a complication of craniocerebral, orbital and facial injuries, leading to irreversible vision loss. At p … riments were conducted to investigate the loss of RGCs and activation or inactivation of microglia, astrocytes and Müller glial cells in the retina from the first week to the fourth week after modeling. The results showed that this minimally invasive method caused damage to the distal optic nerve and loss of RGC after optic nerve injury. Microglia cells were …

Differential effects of SARS-CoV-2 variants on central nervous system cells and blood-brain barrier functions.

BACKGROUND: Although mainly causing a respiratory syndrome, numerous neurological symptoms have been identified following of SARS-CoV-2 infection. However, how the virus affects the brain and how the mutations carried by the different variants modulate those neurological symptoms remain unclear. METHODS: We used primary human pericytes, foetal astrocytes, endothelial cells and a microglial cell line to investigate the effect of several SARS-CoV-2 variants of concern or interest on their functional activities. Cells and a 3D blood-brain barrier model were infected with the wild-type form of SA…

Preserving Brain LPC-DHA by Plasma Supplementation Attenuates Brain Injury after Cardiac Arrest.

OBJECTIVE: Cardiac arrest (CA) is a major health burden with brain damage being a significant contributor to mortality. We found lysophospha … plasma LPC-DHA normalized brain levels of LPC-DHA and alleviated neuronal cell death, activation of astrocytes, and expression of various inflammatory and mitochondrial dynamics genes. We also observed deceased severity of metabolic alterations with LPC-DHA supplementation using untargeted metabolomics analysis. Furthermore, LPC treatment showed a similar pr …

Human Borna disease virus 1 encephalitis shows marked pro-inflammatory biomarker and tissue immunoactivation during the course of disease.

Human Borna disease virus 1 (BoDV-1) encephalitis is a severe emerging disease with a very high case-fatality rate. While the clinical disea … minantly pro-inflammatory pattern over time. IFNγ production was demonstrated in endothelial cells, astrocytes and microglia, IL-6 in activated microglia, and TGF-β1 in endothelial cells, activated astrocytes and microglia. This was paralleled by an increase of chemokines (CCL-2, CCL-5, CXCL-10, IL-8) to attract immune cells to the site of infection, contrib …

Inhibitory Effects of Trifluoperazine on Peripheral Proinflammatory Cytokine Expression and Hypothalamic Microglia Activation in Obese Mice Induced by Chronic Feeding With High-Fat-Diet.

Microglia and astrocytes are the glial cells of the central nervous system (CNS) to support neurodevelopment and neuronal function. Yet, their activation in association with CNS inflammation is involved in the initiation and progression of neurological disorders. Mild inflammation in the periphery and glial activation called as gliosis in the hypothalamic region, arcuate nucleus (ARC), are generally observed in obese individuals and animal models. Thus, reduction in peripheral and central inflammation is considered as a strategy to lessen the abnormality of obesity-associated metabolic indices…