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A microphysiological spheroid system for modeling glioblastoma structure and therapy response.

Glioblastoma (GBM) is a lethal, highly aggressive primary brain tumor. Even with maximal surgical resection, chemo, and radiotherapy, the me … s of increasing complexity: tumor-only (G1), tumor-microglia (G2), and a full niche model including astrocytes (G3). These spheroids exhibited realistic growth dynamics, viability, and morphometric properties. Spheroids were treated with chemotherapeutic drugs: Doxorubicin and Carboplatin. Interestingly, while drug treatment induced cell death in the simpler …

METTL16 Promotes Cerebral Ischemia-Reperfusion Injury via m6A-Dependent Upregulation of TIPARP.

BACKGROUND: Ischemic stroke leads to severe cerebral ischemia/reperfusion (I/R) injury, resulting in neuronal death and neurological deficit … Nissl, NeuN), and apoptosis-related protein expression were evaluated. Primary cortical neurons and astrocytes were subjected to oxygen-glucose deprivation (OGD). Cell apoptosis, LDH release, inflammatory cytokines (TNF-α, IL-1β), and synaptic protein (Synapsin-1, PSD-95) expression were assessed. The METTL16-TIPARP interaction and m6A modification were anal …

Single-nucleus RNA sequencing identifies transcriptomic signatures of alcohol use disorder in the human ventral tegmental area.

BACKGROUND: Alcohol use disorder (AUD) is associated with altered gene expression across diverse cell types in reward-related brain regions, … sessed by gene set enrichment analysis. RESULTS: Nuclei were classified into six major cell types: astrocytes, endothelial cells, mature neurons, microglia, oligodendrocytes, and oligodendrocyte precursor cells (OPCs). At thresholds of P < 0.05 and |fold change| > 2.0, we identified 547 DEGs in astrocytes, 727 DEGs in endothelial cells, 715 DEGs in mature n …

Age-Related Metabolic Vulnerability of Glia in Intracerebral Hemorrhage: Mechanisms and Therapeutic Opportunities.

Intracerebral hemorrhage (ICH), caused by the rupture of blood vessels within the brain parenchyma, represents the most severe form of stroke, characterized by the highest mortality rate and predominantly affecting the elderly population. Glial cells, including microglia, astrocytes, and oligodendrocytes, serve as the resident immune cells of the central nervous system and undergo significant metabolic reprogramming following ICH. Microglia exhibit dual roles in post-ICH tissue damage by altering their polarization states: they contribute to secondary brain injury through pro-inflammatory resp…

NLX-112, a Selective 5-HT1A Receptor Agonist, Upregulates GDNF and is Neuroprotective Against MPTP-Induced Nigrostriatal Degeneration in a Mouse Model of Parkinson's Disease.

NLX-112 is a potent and selective 5-HT1A agonist that has successfully completed a Phase 2A clinical trial for the treatment of L-DOPA-induc … PTP-induced dopamine nerve terminal loss to 30%. MPTP also markedly increased the levels of GFAP-ir astrocytes and Iba1-ir microglia in the SN, as well as coexpression of glial-derived neurotrophic factor (GDNF) in the GFAP-ir astrocytes in both the SNc and the striatum. NLX-112 markedly reversed this MPTP-induced microglial overactivation in the SNc, and up …

Synergistic In Vitro Effects of Minor Phytocannabinoids and Melatonin Combinations Against Human Glioblastoma Cells.

The prognosis of glioblastoma (GBM) patients remains dismal due to chemoresistance. Repurposing of natural and endogenous compounds, such as … y, synergy (Bliss model), and selectivity were evaluated in U87, T98, and U251 GBM lines and normal astrocytes. Mechanisms of damage were characterized via Western blot (γH2AX and PARP-1), flow cytometry using fluorescent dyes/probes (DCFDA, JC-1, MitoBright, BODIPY, PI, and Annexin-V), or the protein marker COX IV and confocal analysis. The results demonstr …

Progressive neuroinflammation and deficits in motor function in a mouse model with an Epg5 pathogenic variant of Vici syndrome.

BACKGROUND: Vici syndrome (VS) is a rare pediatric genetic disorder characterized by profound developmental delay, seizures, immune deficits … f age, which worsen over time. Histological analysis revealed widespread expansion of microglia and astrocytes throughout the central nervous system (CNS). Transcriptomic profiling of CNS tissue revealed robust neuroinflammatory signatures, implicating the activation of both microglia and astrocytes. Notably, the molecular profiles of Epg5 -deficient mice sh …

Electroacupuncture stimulation inhibited astrogliosis and microglia polarisation to alleviate spinal cord injury via Janus kinase 2/signal transducer and activator of transcription 3 signalling pathway.

INTRODUCTION: The aberrant activation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signalling pathway is involved in spinal cord injury (SCI) progression. Electroacupuncture (EA) stimulation is effective in alleviating SCI, but the mechanism is poorly understood. MATERIAL AND METHODS: An SCI model was constructed by cord contusion at T10, and AG490 (a JAK2 inhibitor) served as a positive control in this study. We evaluated the effects of EA on locomotor activity and spinal damage in SCI rats. The effects of EA on astrocytes and microglia and on the JAK…

Generation of hiPSC-Derived Brain Microvascular Endothelial Cells Using Directed Differentiation and Transcriptional Reprogramming.

BACKGROUND: Modeling the human blood-brain barrier (BBB) is limited by the lack of robust protocols to generate induced pluripotent stem cel … alyses, and bulk RNA sequencing to characterize these cells. We cocultured rBMECs with iPSC-derived astrocytes and pericytes in the MIMETAS microfluidics platform to assess how 3-dimensional culture influences their BBB properties. Finally, we generated rBMECs expressing familial Alzheimer disease mutation APP V717I to elucidate how this genetic variant affe …

Activation of Ca2+-sensing receptor exhibited differential response between neurons and glial cells.

The interaction between neurons and glial cells is garnering increased focus due to its significance in understanding neurodegenerative diso … Ca2+ responses profile towards understanding their functional crosstalk. Compared to microglia and astrocytes, oligodendrocytes showed a steeper Ca2+ rise, but the increase in [Ca2+]i in glial cells was distributed between the cellular compartments, except for in astrocytes. Ca2+ release of each neuronal component appeared to rise steadily, while the averag …

A Potential Link Between Early Onset Reactive Astrogliosis and Adult-Onset Dysfunction of Leptin Signaling in Polyubiquitin Gene Ubb Knockout Mice.

BACKGROUND: Polyubiquitin gene Ubb knockout (KO) mice exhibit early onset reactive astrogliosis and adult-onset hypothalamic neurodegenerati … -seq analysis and quantitative reverse transcription-polymerase chain reaction were used. Moreover, astrocytes isolated from postnatal brains were cultured and pure astrocytes were obtained by magnetic-activated cell sorting. Furthermore, mice were challenged with lipopolysaccharide (LPS) to induce upregulation of neuroinflammatory markers, including lipocal …

Ferulic Acid Alleviates Traumatic Brain Injury and Gastrointestinal Disorders by Promoting Ghrelin to Regulate the Microbiota-Brain-Gut Axis Inflammation and Pyroptosis.

Traumatic brain injury (TBI) is a severe condition with a high mortality rate, affecting multiple organs, including the gastrointestinal (GI) tract. Ghrelin is a brain-gut peptide that regulates the microbiota-brain-gut axis, facilitating communication between the GI tract and the central nervous system. This study aimed to investigate the role of ferulic acid (FA) in regulating Ghrelin to improve TBI and GI disorders (GID) induced by controlled cortical impact (CCI). This study used CCI as the in vivo TBI model and scratch-induced injury of primary astrocytes as the in vitro TBI model. The ro…

Multiparametric MRI assessment of acute neuroinflammation in a murine model of peripheral LPS stimulation.

BACKGROUND: Neuroinflammation is implicated in the pathogenesis of several central nervous system disorders. Excessive and prolonged neuroin … rised cytokine/chemokine measurements in the blood and brain, immunohistochemistry of microglia and astrocytes, and brain autoradiography using the TSPO radiotracer [3H]PK11195. BLZ945 (200 mg/kg p.o. daily) was given from day - 7 to day 4. RESULTS: On day 4 of LPS administration, T2-weighted signal and MTR increased, while ADC decreased in several brain re …

A Targeted Radiotheranostic Agent for Glioblastoma: [64Cu]Cu-NOTA-TP-c(RGDfK).

Glioblastoma multiforme (GBM) remains one of the most aggressive and treatment-resistant brain tumors, with poor prognosis and limited thera … Comparative cellular studies were conducted using U87 MG glioblastoma (GBM) cells and SVG p12 human astrocytes to evaluate the performance of [64Cu]Cu-NOTA-TP-c(RGDfK) relative to [64Cu]Cu-NOTA-c(RGDfK), [64Cu]Cu-NOTA-TP, natCu-NOTA-TP-c(RGDfK), cisplatin, and temozolomide. Results: 64Cu-radiolabeling of NOTA-TP-c(RGDfK) was achieved with >99% radiochemical …

Iconography of abnormal non-neuronal cells in pediatric focal cortical dysplasia type IIb and tuberous sclerosis complex.

Once believed to be the culprits of epileptogenic activity, the functional properties of balloon/giant cells (BC/GC), commonly found in some … ization of abnormal non-neuronal cells including BC/GC, intermediate cells, and dysmorphic/reactive astrocytes found in FCDIIb and TSC cases, with special emphasis on electrophysiological and morphological assessments. Regardless of pathology, the electrophysiological properties of abnormal cells appear more glial-like, while others appear more neuronal-like …

[Neuronal intranuclear inclusion disease diagnosed by brain biopsy: a clinicopathological analysis of seven cases].

Objective: To investigate the clinical, imaging and neuropathological characteristics of neuronal intranuclear inclusion disease (NIID) with … that matched those on images and initial symptoms. There were proliferation of oligodendrocytes and astrocytes in the white matter, leukoaraiosis and edema, cortical disintegration and lamellar necrosis, as well as infiltration of lymphocytes and microglia, etc. However, the characteristic changes were eosinophilic hyaline inclusions in the nuclei of neurons …

MiRNA-501-3p and MiRNA-502-3p: A promising biomarker panel for Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) lacks a less invasive and early detectable biomarker. Here, we investigated the biomarker potential o … acellularly and secreted extracellularly in response to APP and Tau pathology. Finally, neurons and astrocytes displayed high expression of these miRNAs. DISCUSSION: These results suggest that miR-501-3p and miR-502-3p could be promising biomarkers for AD. KEY POINTS: MiR-501-3p and miR-502-3p expression is elevated in AD CSF exosomes, AD serum exosomes, A …

NLRX1 limits inflammatory neurodegeneration in the anterior visual pathway.

Chronic innate immune activation in the central nervous system (CNS) significantly contributes to neurodegeneration in progressive multiple … ce, suggesting a regulatory role of NLRX1 in innate immune cells. Transcriptome analysis in primary astrocytes activated with LPS and IFNγ demonstrated that NLRX1 suppresses NF-κB activation and regulates mitochondrial oxidative phosphorylation in inflammatory reactive astrocytes. The novel pharmacologic NLRX1 activators NX-13 and LABP-66 decreased LPS-media …

Microglia contribute to the production of the amyloidogenic ABri peptide in familial British dementia.

Mutations in ITM2B cause familial British, Danish, Chinese, and Korean dementias. In familial British dementia (FBD), a mutation in the stop … TM2B/BRI2 is 34-fold higher in microglia than neurons and 15-fold higher in microglia compared with astrocytes. This cell-specific enrichment is supported by expression data from both mouse and human brain tissue. ITM2B/BRI2 protein levels are higher in iPSC-microglia compared with neurons and astrocytes. The ABri peptide was detected in patient iPSC-derived …

Fibrotic Response in Pericite Cultural после воздействия склерозовой серы.

ВВЕДЕНИЕ: Множественный склероз (МС) представляет собой хроническое аутоиммунное и демиелинизирующее заболевание центральной нервной системы (ЦНС), приводящее к постепенной потере функции. Помимо инфильтрации периферийных иммунных клеток в CNS после нейроинфламмации, аккумуляция внеклеточной матрицы (ECM) элементов, генерируемых клетками мозгового барьера, в расширенных перивашкулярных пространствах способствует патофизиологии. В этом исследовании мы стремились разработать внутреннюю модель MS для исследования фиброза, вызванного серой или цереброспиновой жидкостью (CSF) пациентов MS, и оценит

Совпадение в аннотации оригинала
INTRODUCTION: Multiple sclerosis (MS) is a chronic autoimmune and demyelinating disease of central nervous system (CNS) leading to progressi … ) cells to this model. METHODS: Human brain vascular pericytes, endothelial cells and normal human astrocytes were cultured and exposed to a cytokine reference control (Transforming growth factor beta 1 (TGF-β1)), healthy human sera, and sera/CSF from treatment naïve relapsing-remitting MS patients with the appropriate dilution dose. The pericytes cell prol …