scholarly journals The growth and expansion of meningeal lymphatic networks are affected in craniosynostosis

2021 ◽  
Author(s):  
Phillip Ang ◽  
Matt Matrongolo ◽  
Max Tischfield
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Transverse Sinus ◽  
Venous Malformations ◽  
Cervical Lymph Nodes ◽  
Lymphatic Function ◽  
Lymphatic Development ◽  
The Central Nervous System ◽  
Dural Venous Sinus ◽  
Molecular Tracers

Congenital skull malformations are associated with vascular anomalies that can impair fluid balance in the central nervous system. We previously reported that humans with craniosynostosis and mutations in TWIST1 have dural venous sinus malformations. It is still unknown whether meningeal lymphatic networks, which are patterned alongside the venous sinuses, are also affected. Using a novel skull flat mounting technique, we show that the growth and expansion of meningeal lymphatics are perturbed in Twist1 craniosynostosis models. Changes to the local meningeal environment, including hypoplastic dura and venous malformations, affect the ability of lymphatic networks to sprout and remodel. Dorsal networks along the transverse sinus are hypoplastic with reduced branching. By contrast, basal networks closer to the skull base are more variably affected, showing exuberant growth in some animals suggesting they are compensating for vessel loss in dorsal networks. Injecting molecular tracers into cerebrospinal fluid reveals significantly less drainage to the deep cervical lymph nodes, indicative of impaired lymphatic function. Collectively, our results show that meningeal lymphatic development is hindered in craniosynostosis, suggesting central nervous system waste clearance may be impeded.

scholarly journals The growth and expansion of meningeal lymphatic networks are affected in craniosynostosis

Development ◽  
2021 ◽  
Author(s):  
Phillip S. Ang ◽  
Matt J. Matrongolo ◽  
Max A. Tischfield
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Transverse Sinus ◽  
Venous Malformations ◽  
Cervical Lymph Nodes ◽  
Lymphatic Function ◽  
The Central Nervous System ◽  
Molecular Tracer ◽  
Dural Venous Sinus

Skull malformations are associated with vascular anomalies that can impair fluid balance in the central nervous system. We previously reported that humans with craniosynostosis and mutations in TWIST1 have dural venous sinus malformations. It is still unknown whether meningeal lymphatic networks, which are patterned alongside the venous sinuses, are also affected. We now show that the growth and expansion of meningeal lymphatics are perturbed in Twist1 craniosynostosis models. Changes to the local meningeal environment, including hypoplastic dura and venous malformations, affect the ability of lymphatic networks to sprout and remodel. Dorsal networks along the transverse sinus are hypoplastic with reduced branching. By contrast, basal networks closer to the skull base are more variably affected, showing exuberant growth in some animals suggesting they are compensating for vessel loss in dorsal networks. Injecting a molecular tracer into cerebrospinal fluid reveals significantly less drainage to the deep cervical lymph nodes, indicative of impaired lymphatic function. Collectively, our results show that meningeal lymphatic networks are affected in craniosynostosis, suggesting the clearance of beta-amyloid and waste from the central nervous system may be impeded.

scholarly journals Immunization with dendritic cells can break immunological ignorance toward a persisting virus in the central nervous system and induce partial protection against intracerebral viral challenge

2004 ◽  
Vol 85 (8) ◽  
pp. 2379-2387 ◽  
Author(s):  
Ulrike Fassnacht ◽  
Andreas Ackermann ◽  
Peter Staeheli ◽  
Jürgen Hausmann
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Recombinant Vaccinia Virus ◽  
Immune Memory ◽  
Cervical Lymph Nodes ◽  
The Central Nervous System

Dendritic cells (DCs) have been used successfully to induce CD8 T cells that control virus infections and growth of tumours. The efficacy of DC-mediated immunization for the control of neurotropic Borna disease virus (BDV) in mice was evaluated. Certain strains of mice only rarely develop spontaneous neurological disease, despite massive BDV replication in the brain. Resistance to disease is due to immunological ignorance toward BDV antigen in the central nervous system. Ignorance in mice can be broken by immunization with DCs coated with TELEISSI, a peptide derived from the N protein of BDV, which represents the immunodominant cytotoxic T lymphocyte epitope in H-2k mice. Immunization with TELEISSI-coated DCs further induced solid protective immunity against intravenous challenge with a recombinant vaccinia virus expressing BDV-N. Interestingly, however, this immunization scheme induced only moderate protection against intracerebral challenge with BDV, suggesting that immune memory raised against a shared antigen may be sufficient to control a peripherally replicating virus, but not a highly neurotropic virus that is able to avoid activation of T cells. This difference might be due to the lack of BDV-specific CD4 T cells and/or inefficient reactivation of DC-primed, BDV-specific CD8 T cells by the locally restricted BDV infection. Thus, a successful vaccine against persistent viruses with strong neurotropism should probably induce antiviral CD8 (as well as CD4) T-cell responses and should favour the accumulation of virus-specific memory T cells in cervical lymph nodes.

Extracranial Metastases of Oligodendroglioma

Neurosurgery ◽  
1981 ◽  
Vol 8 (3) ◽  
pp. 391-396 ◽  
Author(s):  
Nelson G. Ordóñez ◽  
Alberto G. Ayala ◽  
Milam E. Leavens
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lymph Nodes ◽  
Masseter Muscle ◽  
Lumbar Vertebrae ◽  
Cervical Lymph Nodes ◽  
Extraneural Metastases ◽  
The Central Nervous System ◽  
The Right ◽  
Extracranial Metastases

Abstract The case of a 33-year-old woman with oligodendroglioma with extraneural metastases involving the masseter muscle, the cervical lymph nodes, the lumbar vertebrae, and the right iliac bone is described. Oligodendroglioma with metastases outside the central nervous system is extremely rare, and only a very few cases have been reported.

scholarly journals Kinetics of Virus-Specific CD8+-T-Cell Expansion and Trafficking following Central Nervous System Infection

2003 ◽  
Vol 77 (4) ◽  
pp. 2775-2778 ◽  
Author(s):  
Norman W. Marten ◽  
Stephen A. Stohlman ◽  
Jiehao Zhou ◽  
Cornelia C. Bergmann
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
T Cell ◽  
Hepatitis Virus ◽  
Acute Infection ◽  
Central Nervous System Infection ◽  
Cervical Lymph Nodes ◽  
Cognate Antigen ◽  
The Central Nervous System

ABSTRACT CD8+ T cells control acute infection of the central nervous system (CNS) by neurotropic mouse hepatitis virus but do not suffice to achieve sterile immunity. To determine the lag between T-cell priming and optimal activity within the CNS, the accumulation of virus-specific CD8+ T cells in the CNS relative to that in peripheral lymphoid organs was assessed by using gamma interferon-specific ELISPOT assays and class I tetramer staining. Virus-specific CD8+ T cells were first detected in the cervical lymph nodes. Expansion in the spleen was delayed and less pronounced but also preceded accumulation in the CNS. The data further suggest peripheral acquisition of cytolytic function, thus enhancing CD8+-T-cell effector function upon cognate antigen recognition in the CNS.

scholarly journals Anatomical Features of the Deep Cervical Lymphatic System and Intrajugular Lymphatic Vessels in Humans

2020 ◽  
Vol 10 (12) ◽  
pp. 953
Author(s):  
Kaan Yağmurlu ◽  
Jennifer D. Sokolowski ◽  
Musa Çırak ◽  
Kamran Urgun ◽  
Sauson Soldozy ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lymphatic Vessels ◽  
Jugular Foramen ◽  
Cervical Lymph Nodes ◽  
Anatomical Features ◽  
Mean Width ◽  
The Central Nervous System ◽  
The Mean ◽  
Rapid Autopsy

Background: Studies in rodents have re-kindled interest in the study of lymphatics in the central nervous system. Animal studies have demonstrated that there is a connection between the subarachnoid space and deep cervical lymph nodes (DCLNs) through dural lymphatic vessels located in the skull base and the parasagittal area. Objective: To describe the connection of the DCLNs and lymphatic tributaries with the intracranial space through the jugular foramen, and to address the anatomical features and variations of the DCLNs and associated lymphatic channels in the neck. Methods: Twelve formalin-fixed human head and neck specimens were studied. Samples from the dura of the wall of the jugular foramen were obtained from two fresh human cadavers during rapid autopsy. The samples were immunostained with podoplanin and CD45 to highlight lymphatic channels and immune cells, respectively. Results: The mean number of nodes for DCLNs was 6.91 ± 0.58 on both sides. The mean node length was 10.1 ± 5.13 mm, the mean width was 7.03 ± 1.9 mm, and the mean thickness was 4 ± 1.04 mm. Immunohistochemical staining from rapid autopsy samples demonstrated that lymphatic vessels pass from the intracranial compartment into the neck through the meninges at the jugular foramen, through tributaries that can be called intrajugular lymphatic vessels. Conclusions: The anatomical features of the DCLNs and their connections with intracranial lymphatic structures through the jugular foramen represent an important possible route for the spread of cancers to and from the central nervous system; therefore, it is essential to have an in-depth understanding of the anatomy of these lymphatic structures and their variations.

scholarly journals Tertiary Lymphoid Structures in the Central Nervous System: Implications for Glioblastoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Tiarne van de Walle ◽  
Alessandra Vaccaro ◽  
Mohanraj Ramachandran ◽  
Ilkka Pietilä ◽  
Magnus Essand ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Brain Tumor ◽  
Tumor Antigen ◽  
Checkpoint Inhibitors ◽  
Cervical Lymph Nodes ◽  
Tertiary Lymphoid Structures ◽  
The Central Nervous System ◽  
Lymphoid Structures

Glioblastoma is the most common and aggressive brain tumor, which is uniformly lethal due to its extreme invasiveness and the absence of curative therapies. Immune checkpoint inhibitors have not yet proven efficacious for glioblastoma patients, due in part to the low prevalence of tumor-reactive T cells within the tumor microenvironment. The priming of tumor antigen-directed T cells in the cervical lymph nodes is complicated by the shortage of dendritic cells and lack of appropriate lymphatic vessels within the brain parenchyma. However, recent data suggest that naive T cells may also be primed within brain tumor-associated tertiary lymphoid structures. Here, we review the current understanding of the formation of these structures within the central nervous system, and hypothesize that promotion of tertiary lymphoid structures could enhance priming of tumor antigen-targeted T cells and sensitize glioblastomas to cancer immunotherapy.

Effects of Hyperoxia on Lung Utrastructure

1970 ◽  
Vol 28 ◽  
pp. 26-27
Author(s):  
Gladys Harrison
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Light Microscopy ◽  
Oxygen Effects ◽  
Age Dependent ◽  
The Central Nervous System ◽  
The Subject ◽  
Space Age ◽  
Alveolar Septa ◽  
Extensive Damage

With the advent of the space age and the need to determine the requirements for a space cabin atmosphere, oxygen effects came into increased importance, even though these effects have been the subject of continuous research for many years. In fact, Priestly initiated oxygen research when in 1775 he published his results of isolating oxygen and described the effects of breathing it on himself and two mice, the only creatures to have had the “privilege” of breathing this “pure air”.Early studies had demonstrated the central nervous system effects at pressures above one atmosphere. Light microscopy revealed extensive damage to the lungs at one atmosphere. These changes which included perivascular and peribronchial edema, focal hemorrhage, rupture of the alveolar septa, and widespread edema, resulted in death of the animal in less than one week. The severity of the symptoms differed between species and was age dependent, with young animals being more resistant.

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