Biological functions of lymphatic vessels

Science, Journal Year: 2020, Volume and Issue: 369(6500)

Published: July 9, 2020

Roles of organ-specific lymphatic vessels Lymphatic are spread throughout the human body and have critical functions in mammalian physiology. Petrova et al. review emerging roles vasculature organ function pathology provide perspectives beyond traditional view maintenance fluid homeostasis. The authors highlight new insights into vessel endothelial cell biology as it relates to intestinal lacteals, lymph nodes, central nervous system meninges, cancer. Recent steps toward therapeutic opportunities that could alter or growth also discussed. Science , this issue p. eaax4063

Language: Английский

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Fluid transport in the brain

Physiological Reviews, Journal Year: 2021, Volume and Issue: 102(2), P. 1025 - 1151

Published: May 5, 2021

The brain harbors a unique ability to, figuratively speaking, shift its gears. During wakefulness, the is geared fully toward processing information and behaving, while homeostatic functions predominate during sleep. blood-brain barrier establishes stable environment that optimal for neuronal function, yet imposes physiological problem; transcapillary filtration forms extracellular fluid in other organs reduced to minimum brain. Consequently, depends on special [the cerebrospinal (CSF)] flushed into along perivascular spaces created by astrocytic vascular endfeet. We describe this pathway, coined term glymphatic system, based dependency endfeet their adluminal expression of aquaporin-4 water channels facing CSF-filled spaces. Glymphatic clearance potentially harmful metabolic or protein waste products, such as amyloid-β, primarily active sleep, when drivers, cardiac cycle, respiration, slow vasomotion, together efficiently propel CSF inflow periarterial brain's space contains an abundance proteoglycans hyaluronan, which provide low-resistance hydraulic conduit rapidly can expand shrink sleep-wake cycle. system brain, meets requisites maintain homeostasis similar peripheral organs, considering blood-brain-barrier paths formation egress CSF.

Language: Английский

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Diffuse Glioma Heterogeneity and Its Therapeutic Implications

Cancer Discovery, Journal Year: 2021, Volume and Issue: 11(3), P. 575 - 590

Published: Feb. 8, 2021

Diffuse gliomas represent a heterogeneous group of universally lethal brain tumors characterized by minimally effective genotype-targeted therapies. Recent advances have revealed that remarkable level genetic, epigenetic, and environmental heterogeneity exists within each individual glioma. Together, these interconnected layers intratumoral result in extreme phenotypic at the cellular level, providing for multiple mechanisms therapeutic resistance forming highly adaptable resilient disease. In this review, we discuss how glioma malignant state plasticity drive to existing therapies look future which challenges may be overcome. SIGNIFICANCE: Glioma cell formidable hurdles development novel targeted However, convergence genotypically diverse cells into limited set epigenetically encoded transcriptional states present an opportunity strategy call "State Selective Lethality." approach, (as opposed genetic perturbations/mutations) are subject targeting, plasticity-mediated is minimized through design "trapping agents."

Language: Английский

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Neuropsychiatric lupus: new mechanistic insights and future treatment directions

Nature Reviews Rheumatology, Journal Year: 2019, Volume and Issue: 15(3), P. 137 - 152

Published: Jan. 18, 2019

Language: Английский

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Glymphatic System Impairment in Alzheimer’s Disease and Idiopathic Normal Pressure Hydrocephalus

Trends in Molecular Medicine, Journal Year: 2020, Volume and Issue: 26(3), P. 285 - 295

Published: Jan. 18, 2020

Language: Английский

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Aging, Melatonin, and the Pro- and Anti-Inflammatory Networks

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(5), P. 1223 - 1223

Published: March 11, 2019

Aging and various age-related diseases are associated with reductions in melatonin secretion, proinflammatory changes the immune system, a deteriorating circadian sirtuin-1 (SIRT1) activity. In non-tumor cells, several effects of abolished by inhibiting SIRT1, indicating mediation SIRT1. Melatonin is, addition to its antioxidant roles, an stimulatory agent. However, it can act as either pro- or anti-inflammatory regulator context-dependent way. stimulate release cytokines other mediators, but also, under different conditions, suppress inflammation-promoting processes such NO release, activation cyclooxygenase-2, inflammasome NLRP3, gasdermin D, toll-like receptor-4 mTOR signaling, cytokine SASP (senescence-associated secretory phenotype), amyloid-β toxicity. It also activates network, which SIRT1 activation, upregulation Nrf2 downregulation NF-κB, IL-4 IL-10 involved. A perhaps crucial action may be promotion macrophage microglia polarization favor phenotype M2. addition, many factors networks subject regulation microRNAs that target mRNAs respective upregulate them targeting their inhibitor proteins.

Language: Английский

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Beyond the neuron–cellular interactions early in Alzheimer disease pathogenesis

Nature reviews. Neuroscience, Journal Year: 2019, Volume and Issue: 20(2), P. 94 - 108

Published: Jan. 14, 2019

Language: Английский

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Understanding the role of the perivascular space in cerebral small vessel disease

Cardiovascular Research, Journal Year: 2018, Volume and Issue: 114(11), P. 1462 - 1473

Published: May 2, 2018

Small vessel diseases (SVDs) are a group of disorders that result from pathological alteration the small blood vessels in brain, including arteries, capillaries and veins. Of 35–36 million people estimated to suffer dementia worldwide, up 65% have an SVD component. Furthermore, causes 20–25% strokes, worsens outcome after stroke is leading cause disability, cognitive impairment poor mobility. Yet underlying cause(s) not fully understood. Magnetic resonance imaging has confirmed enlarged perivascular spaces (PVS) as hallmark feature SVD. In healthy tissue, these proposed form part complex brain fluid drainage system which supports interstitial exchange may also facilitate clearance waste products brain. The pathophysiological signature PVS what this infers about their function interaction with cerebral microcirculation, plus subsequent downstream effects on lesion development been established. Here we discuss potential be unique biomarker for related vascular We propose widening suggests presence peri-vascular cell debris other vicious cycle involving impaired cerebrovascular reactivity, blood-brain barrier dysfunction, inflammation ultimately proteins space, accumulation toxins, hypoxia, tissue damage. Here, outline current knowledge, questions hypotheses regarding understanding dynamics underpinning through common denominator

Language: Английский

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Blocking meningeal lymphatic drainage aggravates Parkinson’s disease-like pathology in mice overexpressing mutated α-synuclein

Translational Neurodegeneration, Journal Year: 2019, Volume and Issue: 8(1)

Published: March 1, 2019

Abnormal aggregation of brain α-synuclein is a central step in the pathogenesis Parkinson's disease (PD), thus, it reliable to promote clearance prevent and treat PD. Recent studies have revealed an essential role glymphatic system meningeal lymphatic vessels macromolecules, however, their pathophysiological aspects remain elusive.Meningeal drainage 18-week-old A53T mice was blocked via ligating deep cervical lymph nodes. Six weeks later, functions PD-like phenotypes were systemically analyzed.Glymphatic influx cerebrospinal fluid tracer reduced mice, accompanied with perivascular impaired polarization aquaporin 4 expression substantia nigra. Cervical ligation aggravated dysfunction causing more severe accumulation α-synuclein, glial activation, inflammation, dopaminergic neuronal loss motor deficits.The results suggest that may be aggravating factor PD pathology.

Language: Английский

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Mechanisms of cognitive dysfunction in CKD

Nature Reviews Nephrology, Journal Year: 2020, Volume and Issue: 16(8), P. 452 - 469

Published: March 31, 2020

Language: Английский

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