Ependymal cells: roles in central nervous system infections and therapeutic application

Journal of Neuroinflammation, Год журнала: 2024, Номер 21(1)

Опубликована: Окт. 9, 2024

Ependymal cells are arranged along the inner surfaces of ventricles and central canal spinal cord, providing anatomical, physiological immunological barriers that maintain cerebrospinal fluid (CSF) homeostasis. Based on this, studies have found alterations in gene expression, cell junctions, cytokine secretion metabolic disturbances can lead to dysfunction ependymal cells, thereby participating onset progression nervous system (CNS) infections. Additionally, exhibit proliferative regenerative potential as well secretory functions during CNS injury, contributing neuroprotection post-injury recovery. Currently, primarily focus basic investigations their morphology, function expression; however, there is a notable lack clinical translational examining molecular mechanisms by which involved disease progression. This limits our understanding infections development therapeutic applications. Therefore, this review will discuss mechanism underlying involvement infections, explore for application treatment modalities.

Язык: Английский

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An MRI-informed histo-molecular analysis implicates ependymal cells in the pathogenesis of periventricular pathology in multiple sclerosis

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

Abstract It is now widely recognized that the cerebrospinal fluid (CSF)-adjacent brain surfaces – namely subpial cortical region and ependyma-adjacent periventricular are uniquely susceptible to a distinct, diffuse form of pathology in multiple sclerosis. So-called surface-in gradients predict future disease relapses independent classical white matter lesions thought occur as result cytotoxic factors CSF. Given underlying mechanisms driving appear be they represent novel treatment target. However, exactly how factor entry into regulated at these CSF-facing borders not understood, particularly ventricular interface. Indeed, although studies have indicated ependymal cells may damaged MS, there has yet comprehensive assessment cell health disease. We employed ultra-high-field MRI-guided immunohistochemistry, electron microscopy, multiomic single nucleus RNA/ATAC sequencing deeply phenotype human MS. Our data revealed direct correlate immune-responsive, reactive state assumed by associated with widespread transporter junctional protein gene dysregulation. then further defined regulatory networks underpinning MS state, predicted ligands known enriched CSF could drive emergence this tested one candidate vivo . found IFNγ increased murine permeability conditional knockout interferon gamma receptor 1 (Ifngr1) was sufficient reverse effect. directly implicate dysregulation More widely, we denote modulatory capacity on function influence inflammatory status region.

Язык: Английский

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Age-related cerebral ventriculomegaly occurs in patients with primary ciliary dyskinesia

Fluids and Barriers of the CNS, Год журнала: 2025, Номер 22(1)

Опубликована: Янв. 31, 2025

Primary ciliary dyskinesia (PCD) is a genetic disorder causing motile dysfunction primarily affecting the respiratory and reproductive systems. However, impact of PCD on central nervous system remains poorly understood. Rodent models exhibit marked hydrocephalus leading to early animal mortality, however, most humans with do not develop for unknown reasons. We hypothesized that patients sub-clinical ventriculomegaly related ependymal dysfunction. demonstrated highly specific expression levels known PCD-related genes in human brain multiciliated cells (p < 0.0001). To assess ventricular size, computed tomography sinus images from (n = 33) age/sex-matched controls 64) were analysed. Patients displayed significantly larger areas 0.0001) Evans index 0.01), indicating was consistent across all subgroups. Ventricular enlargement correlated positively increasing age compared 0.001). Additionally, chart review high prevalence (39%) neuropsychiatric/neurological disorders adult did correlate degree ventriculomegaly. Our findings suggest may have unrecognized, mild which correlates ageing, potentially attributable Further study required determine causality, whether contributes or other morbidity PCD.

Язык: Английский

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Adherent junctions: physiology, role in hydrocephalus and potential therapeutic targets

IBRO Neuroscience Reports, Год журнала: 2025, Номер 18, С. 283 - 292

Опубликована: Фев. 6, 2025

In all epithelial cells, the adherent junctions (AJs) with cadherin as core play an important role in maintenance of connection and formation apical-basal polarity. The ependymal cells close to ventricular system rely on AJs N-cadherin at maintain their normal morphology function. Therefore, it has impact function disease central nervous system. Hydrocephalus is a pathological phenomenon excessive cerebrospinal fluid accumulating accompanied by continuous dilatation, which can be divided into obstructive hydrocephalus communicating according pathogenesis. Obstructive often associated produced differentiation radial glial cells. etiology mainly related dyskinesia fluid. addition, damage brain barrier lead edema aggravate symptoms. At present, researches pathogenesis are focused development cilia, while less attention been paid molecules such AJs, maintaining polarity This paper discusses preventing preserving regulating number upholding integrity impede exacerbation, provides new direction for study hydrocephalus.

Язык: Английский

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The Role of Ciliated Cells of the Spinal Canal

Cell and Tissue Biology, Год журнала: 2025, Номер 19(3), С. 191 - 205

Опубликована: Апрель 3, 2025

Язык: Английский

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Extracellular vesicles as precision therapeutics for psychiatric conditions: targeting interactions among neuronal, glial, and immune networks

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 8, 2025

The critical role of the immune system in brain function and dysfunction is well recognized, yet development therapies for psychiatric diseases has been slow due to concerns about iatrogenic deficiencies. These are emphasized by lack objective diagnostic tools psychiatry. A promise resolve this conundrum lies exploitation extracellular vesicles (EVs) that physiologically produced or can be synthetized. EVs regulate recipient cell functions offer potential EVs-based therapies. Intranasal administration enables targeting specific regions functions, thereby facilitating design precise treatments diseases. such requires navigating four dynamically interacting networks: neuronal, glial, immune, EVs. networks profoundly influenced fluid distribution. They crucial homeostasis, cellular intercellular communication. Fluid abnormalities, like edema altered cerebrospinal (CSF) dynamics, disrupt these networks, negatively impacting health. deeper understanding above-mentioned vital creating biomarker panels identify distinct patient subsets with similar neuro-behavioral symptoms. Testing functional pathways biomarkers could lead new therapeutic tools. Regulatory approval will depend on robust preclinical data reflecting progress interdisciplinary areas, which pave way innovative treatments. Highly collaborative teams needed achieve ambitious goals.

Язык: Английский

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Role of glial cells in neurotoxicological effects of alcohol

Advances in neurotoxicology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Follow the CSF flow: probing multiciliated ependymal cells in brain pathology

Trends in Molecular Medicine, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Язык: Английский

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