Targetability of the neurovascular unit in inflammatory diseases of the central nervous system DOI

Brandon C. Smith,

Rachel A. Tinkey,

Benjamin C. Shaw

и другие.

Immunological Reviews, Год журнала: 2022, Номер 311(1), С. 39 - 49

Опубликована: Июль 31, 2022

Summary The blood–brain barrier (BBB) is a selectively permeable separating the periphery from central nervous system (CNS). BBB restricts flow of most material into and out CNS, including many drugs that could be used as potent therapies. permeability modulated by several cells are collectively called neurovascular unit (NVU). NVU consists specialized CNS endothelial (ECs), pericytes, astrocytes, microglia, neurons. ECs maintain complex “seal” via tight junctions, forming BBB; breakdown these junctions leads to disruption. Pericytes control vascular within capillaries help basal lamina. Astrocytes much has moved beyond EC layer can form secondary under inflammatory conditions. Microglia survey border for noxious material. Neuronal activity also plays role in maintenance BBB. Since neurons all able modulate BBB, understating contributions each member will potentially uncover novel effective methods delivery neurotherapies CNS.

Язык: Английский

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

и другие.

American Journal Of Pathology, Год журнала: 2021, Номер 191(11), С. 1917 - 1931

Опубликована: Июль 27, 2021

Язык: Английский

Процитировано

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

и другие.

Nature Neuroscience, Год журнала: 2022, Номер 25(8), С. 1034 - 1048

Опубликована: Июль 25, 2022

Язык: Английский

Процитировано

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

и другие.

Neurobiology of Disease, Год журнала: 2021, Номер 161, С. 105561 - 105561

Опубликована: Ноя. 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

Язык: Английский

Процитировано

59
Full spectrum of vitamin D immunomodulation in multiple sclerosis: mechanisms and therapeutic implications DOI Creative Commons
Manon Galoppin, Saniya Kari,

Sasha Soldati

и другие.

Brain Communications, Год журнала: 2022, Номер 4(4)

Опубликована: Июнь 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.

Язык: Английский

Процитировано

47
Microglia Regulate Blood–Brain Barrier Integrity via MiR‐126a‐5p/MMP9 Axis during Inflammatory Demyelination DOI Creative Commons
Zhongwang Yu, Fang Xue, Weili Liu

и другие.

Advanced Science, Год журнала: 2022, Номер 9(24)

Опубликована: Июнь 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.

Язык: Английский

Процитировано

42
How does neurovascular unit dysfunction contribute to multiple sclerosis? DOI Creative Commons
Jake M. Cashion, Kaylene M. Young, Brad A. Sutherland

и другие.

Neurobiology of Disease, Год журнала: 2023, Номер 178, С. 106028 - 106028

Опубликована: Фев. 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.

Язык: Английский

Процитировано

37
Cardiac pericytes mediate the remodeling response to myocardial infarction DOI Creative Commons
Pearl Quijada,

Shuin Park,

Peng Zhao

и другие.

Journal of Clinical Investigation, Год журнала: 2023, Номер 133(10)

Опубликована: Май 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.

Язык: Английский

Процитировано

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

и другие.

Immunity, Год журнала: 2023, Номер 56(12), С. 2790 - 2802.e6

Опубликована: Дек. 1, 2023

Язык: Английский

Процитировано

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

Chien-Huai Chuang,

Chiun Hsu

и другие.

Journal of Biomedical Science, Год журнала: 2024, Номер 31(1)

Опубликована: Фев. 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

Язык: Английский

Процитировано

11
Alterations of the blood-brain barrier during aging DOI

Yufan Cao,

Weihai Xu,

Qing Liu

и другие.

Journal of Cerebral Blood Flow & Metabolism, Год журнала: 2024, Номер 44(6), С. 881 - 895

Опубликована: Март 21, 2024

The blood-brain barrier (BBB) is a complex and dynamic interface that regulates the exchange of molecules cells between blood central nervous system. It undergoes structural functional changes during aging, which may compromise its integrity contribute to pathogenesis neurodegenerative diseases. In recent years, advances in microscopy high-throughput bioinformatics have allowed more in-depth investigation aging mechanisms BBB. This review summarizes age-related alterations BBB structure function from six perspectives: endothelial cells, astrocytes, pericytes, basement membrane, microglia perivascular macrophages, fibroblasts, ranging molecular level human multi-system level. These basic components are essential for proper functioning Recent imaging methods were also reviewed. Elucidation age-associated offer insights into homeostasis provide effective therapeutic strategies protect it aging.

Язык: Английский

Процитировано

11