Neuroinflammation and iron metabolism after intracerebral hemorrhage: a glial cell perspective

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 15, 2025

Intracerebral hemorrhage (ICH) is the most common subtype of hemorrhagic stroke causing significant morbidity and mortality. Previously clinical treatments for ICH have largely been based on a single pathophysiological perspective, there remains lack curative interventions. Following rupture cerebral blood vessels, metabolites activate resident immune cells such as microglia astrocytes, infiltrate peripheral cells, leading to release series inflammatory mediators. Degradation hemoglobin produces large amounts iron ions, an imbalance homeostasis production quantities harmful hydroxyl radicals. Neuroinflammation dysregulation brain metabolism are both important changes in ICH, can exacerbate secondary injury. There inseparable relationship between disorder activated glial after ICH. Glial participate through various mechanisms; meanwhile, accumulation exacerbates neuroinflammation by activating signaling pathways modulating functions so on. This review aims explore from perspective metabolism, linking complex changes, delving into exploration treatment approaches offering insights that could enhance management strategies.

Language: Английский

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Unraveling the complex pathophysiology of white matter hemorrhage in intracerebral stroke: A single‐cell RNA sequencing approach

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(3)

Published: March 1, 2024

Abstract Aim This study aims to elucidate the cellular dynamics and pathophysiology of white matter hemorrhage (WMH) in intracerebral (ICH). Methods Using varying doses collagenase IV, a consistent rat ICH model characterized by pronounced WMH was established. Verification achieved through behavioral assays, hematoma volume, histological evaluations. Single‐cell suspensions from hemorrhaged region ipsilateral striatum on day three post‐ICH were profiled using single‐cell RNA sequencing (scRNA‐seq). Gene Ontology (GO) gene set variation analysis (GSVA) further interpreted differentially expressed genes (DEGs). Results Following induction, there notable increase percentage myeloid cells oligodendrocyte precursor (OPCs), alongside reduction neurons, microglia, oligodendrocytes (OLGs). Post‐ICH showed homeostatic microglia transitioning into pro‐, anti‐inflammatory, proliferative states, influencing lipid metabolic pathways. Myeloid amplified chemokine expression, linked with ferroptosis Macrophages exhibited M1 M2 phenotypes, post‐WMH, macrophages displayed predominance their anti‐inflammatory properties. A surge OPC proliferation aligned enhanced ribosomal signaling, suggesting potential reparative responses post‐WMH. Conclusion The offers valuable insights WMH's complex following ICH, highlighting significance utility scRNA‐seq understanding contributing future cerebrovascular research.

Language: Английский

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Iron homeostasis and post-hemorrhagic hydrocephalus: a review

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

Published: Jan. 12, 2024

Iron physiology is regulated by a complex interplay of extracellular transport systems, coordinated transcriptional responses, and iron efflux mechanisms. Dysregulation metabolism can result in defects myelination, neurotransmitter synthesis, neuronal maturation. In neonates, germinal matrix-intraventricular hemorrhage (GMH-IVH) causes overload as blood breakdown the ventricles brain parenchyma which lead to post-hemorrhagic hydrocephalus (PHH). However, precise mechanisms GMH-IVH results PHH remain elusive. Understanding molecular determinants homeostasis developing may improved therapies. This manuscript reviews various roles has development, characterizes our understanding brain, describes potential cause injury. We also review novel preclinical treatments for IVH that specifically target iron. handling within central nervous system provide basis preventative, targeted iron-mediated pathogenesis PHH.

Language: Английский

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Biomechanical instability of the brain–CSF interface in hydrocephalus

Brain, Journal Year: 2024, Volume and Issue: 147(10), P. 3274 - 3285

Published: May 27, 2024

Hydrocephalus, characterized by progressive expansion of the CSF-filled ventricles (ventriculomegaly), is most common reason for brain surgery. 'Communicating' (i.e. non-obstructive) hydrocephalus classically attributed to a primary derangement in CSF homeostasis, such as choroid plexus-dependent hypersecretion, impaired cilia-mediated flow currents, or decreased reabsorption via arachnoid granulations other pathways. Emerging data suggest that abnormal biomechanical properties parenchyma are an under-appreciated driver ventriculomegaly multiple forms communicating across lifespan. We discuss recent evidence from human and animal studies suggests neurodevelopment congenital hydrocephalus, neurodegeneration elderly normal pressure and, all age groups, inflammation-related neural injury post-infectious post-haemorrhagic can result loss stiffness viscoelasticity parenchyma. Abnormal biomechanics create barrier alterations at brain-CSF interface pathologically facilitates secondary enlargement ventricles, even low intracranial pressures. This 'brain-centric' paradigm has implications diagnosis, treatment study womb tomb.

Language: Английский

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Safety of Indocyanine Green Microdosing for Clinical Imaging of CSF Ventricular Dynamics and Extracranial Outflow

Journal of Neuroimaging, Journal Year: 2025, Volume and Issue: 35(2)

Published: March 1, 2025

ABSTRACT Background and Purpose Intravenous administration of indocyanine green (ICG) has been approved in brain surgeries for decades, yet concerns about neurotoxicity prevent its direct into the cerebrospinal fluid (CSF). Armed with prior animal studies demonstrating feasibility using ICG microdosing CSF, we sought to evaluate nonclinical safety profile obtain surrogate measures adults use human neonates. Methods Evaluation toxicity was conducted mixed primary CNS cell cultures an extended study juvenile rat pups deploying intraventricular injections saline (as control) or ICG. Analysis behavior included Novel Object Place Recognition Test rotarod behavioral tests. Immunohistochemical analysis tumor necrosis factor‐alpha (TNF‐α), oxidative deoxyribonucleic acid damage, microglial activation, neuronal density performed on collected brains. We measured levels (before after intravenous administration) CSF from external ventricular drain catheters 10 brain‐injured adults. Results TNF‐α lactate dehydrogenase assay cytotoxicity showed transient elevations 1 h incubation 1291 µM ICG, but none at below 322 even 24 incubation. Behavioral tests immunohistochemical analyses no differences between ICG‐administered animals controls. Intraventricular concentrations ranged 0.17 7.93 µM, adverse events associated administration. Conclusions With 100 µg maximal neonatal range 1.3 6 5 µM. culture, studies, evidence directly CSF.

Language: Английский

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Preliminary feasibility study on DTI to assess the early brain injury in germinal matrix-intraventricular hemorrhage rats

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 21, 2025

Abstract To evaluate the feasibility and efficacy of diffusion tensor imaging (DTI) for detecting early brain microstructure alterations in germinal matrix-intraventricular hemorrhage (GMH-IVH) rat model. This study used a postnatal day 5 (PND 5) model GMH-IVH. T2-weighted DTI were performed during acute (6 h 24 h) subacute (3d 7d) phases after Four parameters including fractional anisotropy (FA), mean (MD), axial (AD) radial (RD) collected 9 specific regions to assess alterations. Early long-term neurological function tests evaluated. Transcriptome sequencing analysis was also investigate possible underlying mechanisms. Regional abnormalities GMH-IVH observed images that showed significant hypointense striatum region which close matrix. changes Alterations other hippocampus, thalamus, external capsule motor cortex noted, associated with behavioral experiments. Long-term show compared sham group, rats group caused abnormal function. In addition, at GMH-IVH, transcriptome results highly expressed differential genes encode hemoglobin components down-regulate neurodevelopment-related pathways. allows assessment alteration pups, providing great value evaluating deficits.

Language: Английский

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Azithromycin reduces hemoglobin-induced innate neuroimmune activation

Experimental Neurology, Journal Year: 2023, Volume and Issue: 372, P. 114574 - 114574

Published: Oct. 17, 2023

Neonatal intraventricular hemorrhage (IVH) releases blood products into the lateral ventricles and brain parenchyma. There are currently no medical treatments for IVH surgery is used to treat a delayed effect of IVH, post-hemorrhagic hydrocephalus. However, not cure intrinsic injury from performed in subacute time frame. Like many neurological diseases injuries, innate immune activation implicated pathogenesis IVH. Innate pharmaceutically targetable mechanism reduce hydrocephalus after Here, we tested macrolide antibiotic azithromycin, which has immunomodulatory properties, an vitro model microglial using product hemoglobin (Hgb). We then utilized azithromycin our vivo injection ventricle post-natal day 5 rat pups. In both models, modulated by several outcome measures including mitochondrial bioenergetic analysis, cytokine expression flow cytometric analysis. This suggests that safe neonates, could hold promise modulating

Language: Английский

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