Journal ArticleDOI
Drainage of Brain Extracellular Fluid into Blood and Deep Cervical Lymph and its Immunological Significance
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TLDR
Quantification of the connection to lymph in rabbit, cat and sheep, using radiolabeled albumin as a marker of flow, indicates that a minimum of 14 to 47% of protein injected into different regions of brain or cerebrospinal fluid passes through lymph.Abstract:
Cerebral extracellular fluids drain from brain to blood across the arachnoid villi and to lymph along certain cranial nerves (primarily olfactory) and spinal nerve root ganglia. Quantification of the connection to lymph in rabbit, cat and sheep, using radiolabeled albumin as a marker of flow, indicates that a minimum of 14 to 47% of protein injected into different regions of brain or cerebrospinal fluid passes through lymph. The magnitude of the outflow to lymph is at variance with the general assumption that the absence of conventional lymphatics from the brain interrupts the afferent arm of the immune response to brain antigens. The immune response to antigens (albumin or myelin basic protein) introduced into the central nervous system (CNS) has been analysed using a rat model with normal brain barrier permeability. The micro-injection of antigen into brain or cerebrospinal fluid elicits a humoral immune response, with antibody production in cervical lymph nodes and spleen, and also affects cell-mediated immunity. Furthermore, antigen may be more immunogenic when administered into the CNS than into conventional extracerebral sites. Clearly, the afferent arm of the immune response to antigens, within the CNS, is intact. Modern studies suggest that the efferent arm is also intact with passage of activated lymphocytes into the brain. Results support a new view of CNS immunology which incorporates continuous and highly regulated communication between the brain and the immune system in both health and disease.read more
Citations
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Journal ArticleDOI
A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β.
Jeffrey J. Iliff,Minghuan Wang,Minghuan Wang,Yonghong Liao,Benjamin A. Plogg,Weiguo Peng,Georg Andreas Gundersen,Helene Benveniste,G. Edward Vates,Rashid Deane,Steven A. Goldman,Erlend A. Nagelhus +11 more
TL;DR: An anatomically distinct clearing system in the brain that serves a lymphatic-like function is described and may have relevance for understanding or treating neurodegenerative diseases that involve the mis-accumulation of soluble proteins, such as amyloid β in Alzheimer's disease.
Journal ArticleDOI
Structural and functional features of central nervous system lymphatic vessels
Antoine Louveau,Igor Smirnov,Timothy J. Keyes,Jacob D. Eccles,Sherin J. Rouhani,J. David Peske,Noël C. Derecki,David Castle,James Mandell,Kevin S. Lee,Tajie H. Harris,Jonathan Kipnis +11 more
TL;DR: In searching for T-cell gateways into and out of the meninges, functional lymphatic vessels lining the dural sinuses are discovered, which may call for a reassessment of basic assumptions in neuroimmunology and sheds new light on the aetiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction.
Journal ArticleDOI
Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination
Kerstin Berer,Marsilius Mues,Michail Koutrolos,Zakeya Al Rasbi,Marina Boziki,Caroline Johner,Hartmut Wekerle,Gurumoorthy Krishnamoorthy +7 more
TL;DR: It is shown that the commensal gut flora—in the absence of pathogenic agents—is essential in triggering immune processes, leading to a relapsing–remitting autoimmune disease driven by myelin-specific CD4+ T cells.
Journal ArticleDOI
Intranasal delivery to the central nervous system: Mechanisms and experimental considerations
TL;DR: This review focuses on the current understanding of the mechanisms underlying intranasal delivery to the central nervous system involving the olfactory and trigeminal nerves, the vasculature, the cerebrospinal fluid, and the lymphatic system.
Journal ArticleDOI
Cerebral Amyloid Angiopathy: Amyloid β Accumulates in Putative Interstitial Fluid Drainage Pathways in Alzheimer's Disease
TL;DR: In this paper, the authors examined evidence for the hypothesis that amyloid beta is deposited in periarterial interstitial fluid drainage pathways of the brain in Alzheimer's disease and that this contributes significantly to cerebral amymoid angiopathy.
References
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Journal ArticleDOI
Junctions between intimately apposed cell membranes in the vertebrate brain
TL;DR: Endothelial and epithelial tight junctions occlude the interspaces between blood and parenchyma or cerebral ventricles, thereby constituting a structural basis for the blood-brain and blood-cerebrospinal fluid barriers.
Journal ArticleDOI
T-lymphocyte entry into the central nervous system
TL;DR: It is demonstrated that when T‐lymphoblasts are introduced into the circulation they rapidly appear in the CNS tissue, and lymphocytes which have entered, exit within 1 to 2 days.
Book ChapterDOI
Immunologically Privileged Sites
Clyde F. Barker,R.E. Billingham +1 more
TL;DR: The chapter presents a critical account of the status of the known or suspected privileged sites in the body and evaluates their significance from both the immunologic and therapeutic viewpoints.
Journal ArticleDOI
Cellular immune reactivity within the CNS
TL;DR: Using autoaggressive rat T lymphocyte lines specific for defined protein components of peripheral or central myelin to study lymphocyte migration and antigen recognition within the nervous system suggests that the nervoussystem is constantly patrolled by low numbers of activated T cells.
Journal ArticleDOI
The large apparent work capability of the blood‐brain barrier: A study of the mitochondrial content of capillary endothelial cells in brain and other tissues of the rat
TL;DR: The apparent excess metabolic work capability of the BBB suggested by this greater number of mitochondria may be related to maintenance of ion differentials between blood plasma and brain extracellular fluid, to extrachoroidal cerebrospinal fluid formation, or to maintaining the unique structural characteristics of central nervous system capillaries.