Public Volume Electron Microscopy Data: An Essential Resource to Study the Brain Microvasculature DOI Creative Commons
Stephanie Bonney, Vanessa Coelho‐Santos, Sheng‐Fu Huang

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: April 5, 2022

Electron microscopy is the primary approach to study ultrastructural features of cerebrovasculature. However, 2D snapshots a vascular bed capture only small fraction its complexity. Recent efforts synaptically map neuronal circuitry using volume electron have also sampled brain microvasculature in 3D. Here, we perform meta-analysis 7 data sets spanning different species and regions, including two from MICrONS consortium that made segment vasculature addition all parenchymal cell types mouse visual cortex. Exploration these revealed rich information for detailed investigation Neurovascular unit (including, but not limited to, endothelial cells, mural perivascular fibroblasts, microglia, astrocytes) could be discerned across broad microvascular zones. Image contrast was sufficient identify subcellular details, junctions, caveolae, peg-and-socket interactions, mitochondria, Golgi cisternae, microvilli other cellular protrusions potential significance signaling. Additionally, non-cellular structures basement membrane spaces were visible traced between arterio-venous zones along wall. These explorations structural may important functions, such as blood-brain barrier integrity, blood flow control, clearance, bioenergetics. They identified limitations where accuracy consistency segmentation further honed by future efforts. The purpose this article introduce valuable community resources within framework cerebrovascular research. We do so providing an assessment their contents, identifying study, discussing next step ideas refining analysis.

Language: Английский

Interplay between Brain Pericytes and Endothelial Cells in Dementia DOI Creative Commons
Tessa V. Procter, Anna Williams, Axel Montagne

et al.

American Journal Of Pathology, Journal Year: 2021, Volume and Issue: 191(11), P. 1917 - 1931

Published: July 27, 2021

Language: Английский

Citations

72
Neurovascular dysfunction in GRN-associated frontotemporal dementia identified by single-nucleus RNA sequencing of human cerebral cortex DOI
Emma Gerrits, Lucia Giannini,

Nieske Brouwer

et al.

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(8), P. 1034 - 1048

Published: July 25, 2022

Language: Английский

Citations

65
SARS-CoV-2 deregulates the vascular and immune functions of brain pericytes via Spike protein DOI Creative Commons
Rayan Khaddaj‐Mallat,

Natija Aldib,

Maxime Bernard

et al.

Neurobiology of Disease, Journal Year: 2021, Volume and Issue: 161, P. 105561 - 105561

Published: Nov. 13, 2021

Coronavirus disease 19 (COVID-19) is a respiratory illness caused by severe acute syndrome coronavirus-2 (SARS-CoV-2). COVID-19 pathogenesis causes vascular-mediated neurological disorders via elusive mechanisms. SARS-CoV-2 infects host cells the binding of viral Spike (S) protein to transmembrane receptor, angiotensin-converting enzyme 2 (ACE2). Although brain pericytes were recently shown abundantly express ACE2 at neurovascular interface, their response S still be elucidated. Using cell-based assays, we found that expression in human vascular was increased upon exposure. Pericytes exposed underwent profound phenotypic changes associated with an elongated and contracted morphology accompanied enhanced contractile myofibrogenic proteins, such as α-smooth muscle actin (α-SMA), fibronectin, collagen I, neurogenic locus notch homolog protein-3 (NOTCH3). On functional level, exposure promoted acquisition calcium (Ca

Language: Английский

Citations

58
Full spectrum of vitamin D immunomodulation in multiple sclerosis: mechanisms and therapeutic implications DOI Creative Commons
Manon Galoppin, Saniya Kari,

Sasha Soldati

et al.

Brain Communications, Journal Year: 2022, Volume and Issue: 4(4)

Published: June 30, 2022

Abstract Vitamin D deficiency has been associated with the risk of multiple sclerosis, disease activity and progression. Results from in vitro experiments, animal models analysis human samples randomized controlled trials provide comprehensive data illustrating pleiotropic actions on immune system. They globally result immunomodulation by decreasing differentiation effector T B cells while promoting regulatory subsets. also modulates innate such as macrophages, monocytes dendritic cells, acts at level blood–brain barrier reducing cell trafficking. exerts additional within central nervous system microglial astrocytic activation. The immunomodulatory role detected sclerosis suggested its potential therapeutic use for treating sclerosis. In this review, we focus recent published describing biological effects function, activation glial neuroprotective effects. Based current knowledge, discuss optimization interventions patients well new technologies allowing in-depth regulations vitamin D.

Language: Английский

Citations

46
Pathophysiology of myelin oligodendrocyte glycoprotein antibody disease DOI Creative Commons
Osman Corbali, Tanuja Chitnis

Frontiers in Neurology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 28, 2023

Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD) is a spectrum of diseases, including optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, and cerebral cortical encephalitis. In addition to distinct clinical, radiological, immunological features, the infectious prodrome more commonly reported in MOGAD (37–70%) than NMOSD (15–35%). Interestingly, pediatric not aggressive adult-onset MOGAD, unlike multiple sclerosis (MS), where annualized relapse rates are three times higher pediatric-onset MS. pathophysiology driven by attacks during which T cells MOG antibodies cross blood brain barrier (BBB). lesions show perivenous confluent pattern around small veins, lacking radiological central vein sign. Initial activation periphery followed reactivation subarachnoid/perivascular spaces MOG-laden antigen-presenting inflammatory CSF milieu, enables infiltrate CNS parenchyma. CD4+ cells, CD8+ MS, dominant cell type found lesion histology. Granulocytes, macrophages/microglia, activated complement also lesions, could contribute demyelination relapses. potentially pathology opsonizing MOG, activation, antibody-dependent cellular cytotoxicity. Stimulation peripheral MOG-specific B through TLR stimulation or follicular helper might help differentiate antibody-producing plasma blood. Neuroinflammatory biomarkers (such as MBP, sNFL, GFAP, Tau) support that most axonal damage happens initial attack, whereas relapses associated with increased myelin damage.

Language: Английский

Citations

42
Microglia Regulate Blood–Brain Barrier Integrity via MiR‐126a‐5p/MMP9 Axis during Inflammatory Demyelination DOI Creative Commons
Zhongwang Yu, Fang Xue, Weili Liu

et al.

Advanced Science, Journal Year: 2022, Volume and Issue: 9(24)

Published: June 27, 2022

Blood-brain barrier (BBB) impairment is an early prevalent feature of multiple sclerosis (MS), and remains vital for MS progression. Microglial activation precedes BBB disruption cellular infiltrates in the brain patients. However, little known about function microglia impairment. Here, acts as important modulator integrity inflammatory demyelination. depletion profoundly ameliorates experimental autoimmune encephalomyelitis (EAE). Specifically, miR-126a-5p positively correlated with four types plaques. Mechanistically, microglial deletion exacerbates leakage EAE severity. The protective effect mimicked restored by specific inhibition MMP9 microglia. Importantly, Auranofin, FDA-approved drug, identified to protect mitigate progression via a dependent mechanism. Taken together, can be manipulated ameliorate Targeting regulate permeability merits consideration therapeutic interventions MS.

Language: Английский

Citations

40
How does neurovascular unit dysfunction contribute to multiple sclerosis? DOI Creative Commons
Jake M. Cashion, Kaylene M. Young, Brad A. Sutherland

et al.

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 178, P. 106028 - 106028

Published: Feb. 1, 2023

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system (CNS) and most common non-traumatic cause neurological disability in young adults. clinical care has improved considerably due to development disease-modifying therapies that effectively modulate peripheral immune response reduce relapse frequency. However, current treatments do not prevent neurodegeneration progression, efforts multiple will be hampered so long as this remains unknown. Risk factors for or severity include vitamin D deficiency, cigarette smoking youth obesity, which also impact vascular health. People with frequently experience blood-brain barrier breakdown, microbleeds, reduced cerebral blood flow diminished neurovascular reactivity, it possible these pathologies are tied development. The unit a cellular network controls neuroinflammation, maintains integrity, tightly regulates flow, matching energy supply neuronal demand. composed vessel-associated cells such endothelial cells, pericytes astrocytes, however other glial cell types comprise niche. Recent single-cell transcriptomics data, indicate particular microvasculature, compromised within lesions. Large-scale genetic small-scale biology studies suggest dysfunction could primary pathology contributing Herein we revisit risk pathophysiology highlight known potential roles progression. We evaluate suitability target future modifying sclerosis.

Language: Английский

Citations

34
Cardiac pericytes mediate the remodeling response to myocardial infarction DOI Creative Commons
Pearl Quijada,

Shuin Park,

Peng Zhao

et al.

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(10)

Published: May 15, 2023

Despite the prevalence of pericytes in microvasculature heart, their role during ischemia-induced remodeling remains unclear. We used multiple lineage-tracing mouse models and found that migrated to injury site expressed profibrotic genes, coinciding with increased vessel leakage after myocardial infarction (MI). Single-cell RNA-Seq cardiac at various time points MI revealed temporally regulated induction genes related vascular permeability, extracellular matrix production, basement membrane degradation, TGF-β signaling. Deleting receptor 1 chondroitin sulfate proteoglycan 4–expressing (Cspg4-expressing) cells reduced fibrosis following MI, leading a transient improvement ejection fraction. Furthermore, genetic ablation Cspg4-expressing resulted excessive decline function, mortality second week MI. These data reveal an essential for control homeostasis fibrotic response acute ischemic injury, information will help guide development novel strategies preserve integrity attenuate pathological remodeling.

Language: Английский

Citations

28
Circulating senescent myeloid cells infiltrate the brain and cause neurodegeneration in histiocytic disorders DOI Creative Commons
C. Matthias Wilk, Flurin Cathomas, Orsolya Török

et al.

Immunity, Journal Year: 2023, Volume and Issue: 56(12), P. 2790 - 2802.e6

Published: Dec. 1, 2023

Language: Английский

Citations

25
Translational research on drug development and biomarker discovery for hepatocellular carcinoma DOI Creative Commons
Valerie Chew,

Chien-Huai Chuang,

Chiun Hsu

et al.

Journal of Biomedical Science, Journal Year: 2024, Volume and Issue: 31(1)

Published: Feb. 17, 2024

Abstract Translational research plays a key role in drug development and biomarker discovery for hepatocellular carcinoma (HCC). However, unique challenges exist this field because of the limited availability human tumor samples from surgery, lack homogenous oncogenic driver mutations, paucity adequate experimental models. In review, we provide insights into these review recent advancements, with particular focus on two main agents currently used as mainstream therapies HCC: anti-angiogenic immunotherapy. First, examine pre-clinical clinical studies to highlight determining optimal therapeutic combinations biologically effective dosage HCC. Second, discuss focusing anti-PD1/anti-PD-L1-based combination therapy. Finally, progress made our collective understanding immunology multi-omics analysis technology, which enhance mechanisms underlying immunotherapy, characterize different patient subgroups, facilitate novel approaches improve treatment efficacy. summary, provides comprehensive overview efforts translational aiming at advancing improving

Language: Английский

Citations

10