The lymphatic system: A historical perspective

Loukas, Marios; Bellary, Sharath; Kuklinski, Michael; Ferrauiola, Julie; Yadav, Abha; Shoja, Mohammadali Mohajel; Shaffer, Kitt; Tubbs, R. Shane

doi:10.1002/ca.21194

Cited by 44 publications

(53 citation statements)

References 24 publications

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“…Lymphatic vessels have recently been described in the meninges surrounding the mouse brain, 18 but the brain parenchyma itself is devoid of such vessels, leading to the long-held assumption that CSF serves as a ‘lymph equivalent’ to clear waste from the CNS. 74,75 Apart from transport across the endothelium, the removal of ISF from the brain parenchyma was traditionally believed to occur by diffusion 76 or ISF bulk flow into the CSF sink, which comprises the ventricles and subarachnoid space. 77 Given that diffusion is dependent on molecular size, diffusion into the CSF sink has been proposed to be too slow for the highly metabolic and large human brain.…”

Section: Clearance Systemsmentioning

confidence: 99%

Clearance systems in the brain—implications for Alzheimer disease

et al. 2015

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Accumulation of toxic protein aggregates—amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles—is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood–brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ.

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Section: Clearance Systemsmentioning

confidence: 99%

Clearance systems in the brain—implications for Alzheimer disease

et al. 2015

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“…by Hippocrates and Aristotle. Several centuries later, the Greek physician Claudius Galen described mesenteric lymph nodes filled with chyle, or lymph consisting of emulsified fats that originates from the small intestine (623). However, during the middle ages, this knowledge was largely forgotten until 1622 when Gasaro Aselli had the serendipitous finding of “lacteal vessels” while dissecting a live dog’s abdomen.…”

Section: Introduction and Historical Perspectivementioning

confidence: 99%

“…He went on to trace these vessels back to the gut, and observed lymphatic valves that he surmised would prevent backflow. Aselli’s work was published in 1627, after his death, at a time when William Harvey’s theory of the circulation of blood was still novel and revolutionary (28, 337, 623). Several decades later, Jean Pecquet successfully demonstrated that chyle originating from the gut travels through the cisterna chyli and thoracic duct to the right subclavian vein, debunking the popular theory at the time that chyle traveled directly from the intestine to the liver.…”

Section: Introduction and Historical Perspectivementioning

confidence: 99%

Lymphatic Vessel Network Structure and Physiology

Breslin

Yang

Scallan

et al. 2018

Comprehensive Physiology

272

258

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The lymphatic system is comprised of a network of vessels interrelated with lymphoid tissue, which has the holistic function to maintain the local physiologic environment for every cell in all tissues of the body. The lymphatic system maintains extracellular fluid homeostasis favorable for optimal tissue function, removing substances that arise due to metabolism or cell death, and optimizing immunity against bacteria, viruses, parasites, and other antigens. This article provides a comprehensive review of important findings over the past century along with recent advances in the understanding of the anatomy and physiology of lymphatic vessels, including tissue/organ specificity, development, mechanisms of lymph formation and transport, lymphangiogenesis, and the roles of lymphatics in disease.

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“…Lymphatic vessels, which run in parallel with the blood vascular system, are the principal means by which tissues eliminate excess fluid and proteins. Although the density of lymph vessels generally correlates with tissue metabolic rate (4), the brain and spinal cord are curiously devoid of such a lymphatic tree. This is puzzling because the high metabolic activity of neurons predicts the need for rapid elimination of their metabolic byproducts.…”

mentioning

confidence: 99%