How to drain without lymphatics? Dendritic cells migrate from the cerebrospinal fluid to the B-cell follicles of cervical lymph nodes

Blood ◽  
2006 ◽  
Vol 107 (2) ◽  
pp. 806-812 ◽  
Author(s):  
Eric Hatterer ◽  
Nathalie Davoust ◽  
Marianne Didier-Bazes ◽  
Carine Vuaillat ◽  
Christophe Malcus ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Dendritic Cells ◽  
Lymph Nodes ◽  
B Cell ◽  
Subventricular Zone ◽  
Lymphatic Vessels ◽  
Brain Parenchyma ◽  
Cervical Lymph Nodes ◽  
The Central Nervous System ◽  
Anatomic Feature

AbstractThe lack of draining lymphatic vessels in the central nervous system (CNS) contributes to the so-called “CNS immune privilege.” However, despite such a unique anatomic feature, dendritic cells (DCs) are able to migrate from the CNS to cervical lymph nodes through a yet unknown pathway. In this report, labeled bone marrow-derived myeloid DCs were injected stereotaxically into the cerebrospinal fluid (CSF) or brain parenchyma of normal rats. We found that DCs injected within brain parenchyma migrate little from their site of injection and do not reach cervical lymph nodes. In contrast, intra-CSF-injected DCs either reach cervical lymph nodes or, for a minority of them, infiltrate the subventricular zone, where neural stem cells reside. Surprisingly, DCs that reach cervical lymph nodes preferentially target B-cell follicles rather than T-cell-rich areas. This report sheds a new light on the specific role exerted by CSF-infiltrating DCs in the control of CNS-targeted immune responses. (Blood. 2006; 107:806-812)

scholarly journals Cerebrospinal Fluid Dendritic Cells Infiltrate the Brain Parenchyma and Target the Cervical Lymph Nodes under Neuroinflammatory Conditions

PLoS ONE ◽  
2008 ◽  
Vol 3 (10) ◽  
pp. e3321 ◽  
Author(s):  
Eric Hatterer ◽  
Monique Touret ◽  
Marie-Françoise Belin ◽  
Jérôme Honnorat ◽  
Serge Nataf
Keyword(s):  
Cerebrospinal Fluid ◽  
Dendritic Cells ◽  
Lymph Nodes ◽  
Brain Parenchyma ◽  
Cervical Lymph Nodes ◽  
The Brain

Dynamics of Evans blue clearance from cerebrospinal fluid into meningeal lymphatic vessels and deep cervical lymph nodes

2018 ◽  
Vol 40 (5) ◽  
pp. 372-380 ◽  
Author(s):  
Marcela Maloveska ◽  
Jan Danko ◽  
Eva Petrovova ◽  
Lenka Kresakova ◽  
Katarina Vdoviakova ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Lymph Nodes ◽  
Evans Blue ◽  
Lymphatic Vessels ◽  
Cervical Lymph Nodes

The perivascular pathways for influx of cerebrospinal fluid are most efficient in the midbrain

2017 ◽  
Vol 131 (22) ◽  
pp. 2745-2752 ◽  
Author(s):  
Howard Dobson ◽  
Matthew MacGregor Sharp ◽  
Richard Cumpsty ◽  
Theodore P. Criswell ◽  
Tyler Wellman ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Cerebrospinal Fluid ◽  
Subarachnoid Space ◽  
Lymphatic Vessels ◽  
Brain Parenchyma ◽  
Basement Membranes ◽  
Post Mortem ◽  
Cervical Lymph Nodes ◽  
The Brain

Although there are no conventional lymphatic vessels in the brain, fluid and solutes drain along basement membranes (BMs) of cerebral capillaries and arteries towards the subarachnoid space and cervical lymph nodes. Convective influx/glymphatic entry of the cerebrospinal fluid (CSF) into the brain parenchyma occurs along the pial-glial BMs of arteries. This project tested the hypotheses that pial-glial BM of arteries are thicker in the midbrain, allowing more glymphatic entry of CSF. The in vivo MRI and PET images were obtained from a 4.2-year-old dog, whereas the post-mortem electron microscopy was performed in a 12-year-old dog. We demonstrated a significant increase in the thickness of the pial-glial BM in the midbrain compared with the same BM in different regions of the brain and an increase in the convective influx of fluid from the subarachnoid space. These results are highly significant for the intrathecal drug delivery into the brain, indicating that the midbrain is better equipped for convective influx/glymphatic entry of the CSF.

Depletion of Dendritic Cells in Cervical Lymph Nodes and Palatine Tonsils of HIV-Positive Patients

2015 ◽  
Vol 120 (2) ◽  
pp. e93
Author(s):  
BIANCA CARLA BIANCO ◽  
THAIS MAUAD ◽  
LUCIANA SCHULTZ ◽  
ANA LÚCIA NORONHA FRANCISCO ◽  
LUIZ PAULO KOWALSKI ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Lymph Nodes ◽  
Hiv Positive ◽  
Cervical Lymph Nodes ◽  
Palatine Tonsils

Neural glymphatic system: Clinical implications and potential importance of melatonin

2021 ◽  
Vol 4 (4) ◽  
pp. 551-565
Author(s):  
Ryan D Bitar ◽  
Jorge L Torres-Garza ◽  
Russel J Reiter ◽  
William T Phillips
Keyword(s):  
Lymph Nodes ◽  
Subarachnoid Space ◽  
Slow Wave Sleep ◽  
Lymphatic Vessels ◽  
Amyloid Β ◽  
Secretory Product ◽  
Cervical Lymph Nodes ◽  
Waste Products ◽  
Glymphatic System ◽  
The Brain

The central nervous system was thought to lack a lymphatic drainage until the recent discovery of the neural glymphatic system.  This highly specialized waste disposal network includes classical lymphatic vessels in the dura that absorb fluid and metabolic by-products and debris from the underlying cerebrospinal fluid (CSF) in the subarachnoid space. The subarachnoid space is continuous with the Virchow-Robin peri-arterial and peri-vascular spaces which surround the arteries and veins that penetrate into the neural tissue, respectively.  The dural lymphatic vessels exit the cranial vault via an anterior and a posterior route and eventually drain into the deep cervical lymph nodes. Aided by the presence of aquaporin 4 on the perivascular endfeet of astrocytes, nutrients and other molecules enter the brain from peri-arterial spaces and form interstitial fluid (ISF) that baths neurons and glia before being released into peri-venous spaces.  Melatonin, a pineal-derived secretory product which is in much higher concentration in the CSF than in the blood, is believed to follow this route and to clear waste products such as amyloid-β from the interstitial space. The clearance of amyloid-β reportedly occurs especially during slow wave sleep which happens concurrently with highest CSF levels of melatonin.  Experimentally, exogenously-administered melatonin defers amyloid-β buildup in the brain of animals and causes its accumulation in the cervical lymph nodes. Clinically, with increased age CSF melatonin levels decrease markedly, co-incident with neurodegeneration and dementia.  Collectively, these findings suggest a potential association between the loss of melatonin, decreased glymphatic drainage and neurocognitive decline in the elderly.

Cerebrospinal Fluid Cytology of Lyme Neuroborreliosis: A Report of 3 Cases with Literature Review

2015 ◽  
Vol 59 (4) ◽  
pp. 339-344 ◽  
Author(s):  
Juan Xing ◽  
Lisa Radkay ◽  
Sara E. Monaco ◽  
Christine G. Roth ◽  
Liron Pantanowitz
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Lyme Disease ◽  
B Cell ◽  
Plasma Cells ◽  
Lyme Neuroborreliosis ◽  
Chain Analysis ◽  
The Central Nervous System

Lyme disease can affect the central nervous system causing a B-cell-predominant lymphocytic pleocytosis. Since most reactions to infection in the cerebrospinal fluid (CSF) are typically T-cell predominant, a B-cell-predominant lymphocytosis raises concern for lymphoma. We present 3 Lyme neuroborreliosis cases in order to illustrate the challenging cytomorphological and immunophenotypic features of their CSF specimens. Three male patients who presented with central nervous system manifestations were diagnosed with Lyme disease. The clinical presentation, laboratory tests, CSF cytological examination and flow-cytometric studies were described for each case. CSF cytology showed lymphocytic pleocytosis with increased plasmacytoid cells and/or plasma cells. Flow cytometry showed the presence of polytypic B lymphocytes with evidence of plasmacytic differentiation in 2 cases. In all cases, Lyme disease was confirmed by the Lyme screening test and Western blotting. In such cases of Lyme neuroborreliosis, flow cytometry of CSF samples employing plasmacytic markers and cytoplasmic light-chain analysis is diagnostically helpful to exclude lymphoma.

An Experimental Model of Human Leukemic Meningitis in the Nude Rat

Blood ◽  
1997 ◽  
Vol 90 (1) ◽  
pp. 298-305 ◽  
Author(s):  
Tara A. Barone ◽  
Robert J. Plunkett ◽  
Philip Hohmann ◽  
Agnieszka Lis ◽  
Norman Glenister ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Lymph Nodes ◽  
Lymphoblastic Leukemia ◽  
Human Condition ◽  
Leukemic Cells ◽  
Leukemia Cell Line ◽  
Cervical Lymph Nodes ◽  
Nude Rat ◽  
Leukemic Meningitis ◽  
Meningeal Leukemia

Abstract An experimental animal model of meningeal leukemia was developed in the nude rat, rnu/rnu, using the human-derived acute lymphoblastic leukemia cell line HPB-ALL. Anesthetized rats were placed in a modified stereotaxic frame and then injected intrathecally, at the level of the cisterna magna, with human leukemic cells. Cerebrospinal fluid and tissue samples from brain, spinal cord, heart, liver, kidney, spleen, bone marrow, and cervical lymph nodes were subjected to histopathologic examination and molecular genetic screening by clonotype primer-directed polymerase chain reaction (CPD-PCR). Ninety-three percent of animals (n = 14) developed signs of meningeal irritation leading to death 30 to 63 days postinjection (median, 36.0 days, mean, 38.7); death occurred between 30 and 39 days in 77% of all animals. Leukemic cells progressively infiltrated the pericerebellar and pericerebral subarachnoid space and infiltrated the Virchow-Robin (perivascular) space. The infiltrating meningeal leukemia closely resembled the pathologic presentation in the human condition. By CPD-PCR, leukemic cells were first detected in cerebrospinal fluid (CSF ) on day 4 postinjection, were variably present over the ensuing 17 days, and were consistently detected after day 21. At terminal stages, CPD-PCR tissue surveys showed leukemic DNA in all brains and spinal cords and rarely in cervical lymph nodes, but leukemic DNA was not detected in any other tissue screened. Leukemic meningitis was reliably produced with a predictable survival time. Intrathecal administration of leukemic cells was an efficient means of transmitting leukemic meningitis and it compartmentalized the disease to the central nervous system (CNS), eliminating potential complications of systemic illness. The use of human-derived cell lines may render this model more relevant to the development of future therapeutic strategies to treat leukemia and lymphoma that invade the CNS.

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