scholarly journals CNS-Draining Meningeal Lymphatic Vasculature: Roles, Conundrums and Future Challenges

2021 ◽  
Vol 12 ◽  
Author(s):  
Sofia Pereira das Neves ◽  
Nickoleta Delivanoglou ◽  
Sandro Da Mesquita
Keyword(s):  
Neurological Disorders ◽  
Vascular System ◽  
Growth Factor Signaling ◽  
Cervical Lymph Nodes ◽  
Continuous Drainage ◽  
Future Challenges ◽  
Lymphatic Vasculature ◽  
The Central Nervous System ◽  
Functional Features ◽  
To Come

A genuine and functional lymphatic vascular system is found in the meninges that sheath the central nervous system (CNS). This unexpected (re)discovery led to a reevaluation of CNS fluid and solute drainage mechanisms, neuroimmune interactions and the involvement of meningeal lymphatics in the initiation and progression of neurological disorders. In this manuscript, we provide an overview of the development, morphology and unique functional features of meningeal lymphatics. An outline of the different factors that affect meningeal lymphatic function, such as growth factor signaling and aging, and their impact on the continuous drainage of brain-derived molecules and meningeal immune cells into the cervical lymph nodes is also provided. We also highlight the most recent discoveries about the roles of the CNS-draining lymphatic vasculature in different pathologies that have a strong neuroinflammatory component, including brain trauma, tumors, and aging-associated neurodegenerative diseases like Alzheimer’s and Parkinson’s. Lastly, we provide a critical appraisal of the conundrums, challenges and exciting questions involving the meningeal lymphatic system that ought to be investigated in years to come.

scholarly journals A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules

2015 ◽  
Vol 212 (7) ◽  
pp. 991-999 ◽  
Author(s):  
Aleksanteri Aspelund ◽  
Salli Antila ◽  
Steven T. Proulx ◽  
Tine Veronica Karlsen ◽  
Sinem Karaman ◽  
...  
Keyword(s):  
Subarachnoid Space ◽  
Interstitial Fluid ◽  
Vascular System ◽  
Lymphatic Vessels ◽  
Cervical Lymph Nodes ◽  
Brain Interstitial Fluid ◽  
Lymphatic Vasculature ◽  
The Central Nervous System ◽  
Base Of The Skull ◽  
The Brain

The central nervous system (CNS) is considered an organ devoid of lymphatic vasculature. Yet, part of the cerebrospinal fluid (CSF) drains into the cervical lymph nodes (LNs). The mechanism of CSF entry into the LNs has been unclear. Here we report the surprising finding of a lymphatic vessel network in the dura mater of the mouse brain. We show that dural lymphatic vessels absorb CSF from the adjacent subarachnoid space and brain interstitial fluid (ISF) via the glymphatic system. Dural lymphatic vessels transport fluid into deep cervical LNs (dcLNs) via foramina at the base of the skull. In a transgenic mouse model expressing a VEGF-C/D trap and displaying complete aplasia of the dural lymphatic vessels, macromolecule clearance from the brain was attenuated and transport from the subarachnoid space into dcLNs was abrogated. Surprisingly, brain ISF pressure and water content were unaffected. Overall, these findings indicate that the mechanism of CSF flow into the dcLNs is directly via an adjacent dural lymphatic network, which may be important for the clearance of macromolecules from the brain. Importantly, these results call for a reexamination of the role of the lymphatic system in CNS physiology and disease.

scholarly journals Mitochondrial DNA Heteroplasmy as an Informational Reservoir Dynamically Linked to Metabolic and Immunological Processes Associated with COVID-19 Neurological Disorders

2021 ◽  
Author(s):  
George B. Stefano ◽  
Richard M. Kream
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Function ◽  
Neurological Disorders ◽  
Nuclear Dna ◽  
Mitochondrial Dynamics ◽  
Cell Types ◽  
Tissue Specific ◽  
Copy Numbers ◽  
The Central Nervous System ◽  
Mitochondrial Dna Heteroplasmy

AbstractMitochondrial DNA (mtDNA) heteroplasmy is the dynamically determined co-expression of wild type (WT) inherited polymorphisms and collective time-dependent somatic mutations within individual mtDNA genomes. The temporal expression and distribution of cell-specific and tissue-specific mtDNA heteroplasmy in healthy individuals may be functionally associated with intracellular mitochondrial signaling pathways and nuclear DNA gene expression. The maintenance of endogenously regulated tissue-specific copy numbers of heteroplasmic mtDNA may represent a sensitive biomarker of homeostasis of mitochondrial dynamics, metabolic integrity, and immune competence. Myeloid cells, monocytes, macrophages, and antigen-presenting dendritic cells undergo programmed changes in mitochondrial metabolism according to innate and adaptive immunological processes. In the central nervous system (CNS), the polarization of activated microglial cells is dependent on strategically programmed changes in mitochondrial function. Therefore, variations in heteroplasmic mtDNA copy numbers may have functional consequences in metabolically competent mitochondria in innate and adaptive immune processes involving the CNS. Recently, altered mitochondrial function has been demonstrated in the progression of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Accordingly, our review is organized to present convergent lines of empirical evidence that potentially link expression of mtDNA heteroplasmy by functionally interactive CNS cell types to the extent and severity of acute and chronic post-COVID-19 neurological disorders.

scholarly journals Genetic Approaches Using Zebrafish to Study the Microbiota–Gut–Brain Axis in Neurological Disorders

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 566
Author(s):  
Jae-Geun Lee ◽  
Hyun-Ju Cho ◽  
Yun-Mi Jeong ◽  
Jeong-Soo Lee
Keyword(s):  
Neurological Disorders ◽  
Genetic Model ◽  
Molecular Genetic ◽  
Autism Spectrum ◽  
Behavioral Abnormalities ◽  
Bidirectional Signaling ◽  
Intestinal Dysbiosis ◽  
The Central Nervous System ◽  
The Brain

The microbiota–gut–brain axis (MGBA) is a bidirectional signaling pathway mediating the interaction of the microbiota, the intestine, and the central nervous system. While the MGBA plays a pivotal role in normal development and physiology of the nervous and gastrointestinal system of the host, its dysfunction has been strongly implicated in neurological disorders, where intestinal dysbiosis and derived metabolites cause barrier permeability defects and elicit local inflammation of the gastrointestinal tract, concomitant with increased pro-inflammatory cytokines, mobilization and infiltration of immune cells into the brain, and the dysregulated activation of the vagus nerve, culminating in neuroinflammation and neuronal dysfunction of the brain and behavioral abnormalities. In this topical review, we summarize recent findings in human and animal models regarding the roles of the MGBA in physiological and neuropathological conditions, and discuss the molecular, genetic, and neurobehavioral characteristics of zebrafish as an animal model to study the MGBA. The exploitation of zebrafish as an amenable genetic model combined with in vivo imaging capabilities and gnotobiotic approaches at the whole organism level may reveal novel mechanistic insights into microbiota–gut–brain interactions, especially in the context of neurological disorders such as autism spectrum disorder and Alzheimer’s disease.

scholarly journals Meningitis Caused by Salmonella Newport in a Five-Year-Old Child

2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Ana De Malet ◽  
Sheila Ingerto ◽  
Israel Gañán
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Disorders ◽  
Invasive Disease ◽  
Salmonella Typhi ◽  
Gram Negative ◽  
Negative Bacillus ◽  
Salmonella Newport ◽  
Gram Negative Bacillus ◽  
The Central Nervous System

Salmonella Newport is a Gram-negative bacillus belonging to the Enterobacteria family and the nontyphi Salmonella (NTS), usually related to gastroenteritis. Main difference between NTS and Salmonella typhi is that the last one evolves to an invasive disease easier than NTS. These can progress to bacteremias in around 5% of cases and secondary focuses can appear occasionally, as in meningitis. An infection of the central nervous system is uncommon, considering its incidence in 0.6–8% of the cases; most of them are described in developing countries and mainly in childhood, especially neonates. Bacterial meningitis by NTS mostly affects immunosuppressed people in Europe. Prognosis is adverse, with a 50% mortality rate, mainly due to complications of infection: hydrocephalus, ventriculitis, abscesses, subdural empyema, or stroke. Choice antibiotic treatments are cefotaxime, ceftriaxone, or ceftazidime. The aim of this paper is to present a case of meningitis caused by Salmonella Newport diagnosed in a five-year-old girl living in a rural area of the province of Ourense (Spain), with favorable evolution and without neurological disorders.

scholarly journals Intestinal Microbiota as an Alternative Therapeutic Target for Epilepsy

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Jiaying Wu ◽  
Yuyu Zhang ◽  
Hongyu Yang ◽  
Yuefeng Rao ◽  
Jing Miao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Intestinal Microbiota ◽  
Neurological Disorders ◽  
Digestive System ◽  
Hygiene Hypothesis ◽  
Host Susceptibility ◽  
Immune Disorders ◽  
The Central Nervous System ◽  
Symbiotic Microbiota

Epilepsy is one of the most widespread serious neurological disorders, and an aetiological explanation has not been fully identified. In recent decades, a growing body of evidence has highlighted the influential role of autoimmune mechanisms in the progression of epilepsy. The hygiene hypothesis draws people’s attention to the association between gut microbes and the onset of multiple immune disorders. It is also believed that, in addition to influencing digestive system function, symbiotic microbiota can bidirectionally and reversibly impact the programming of extraintestinal pathogenic immune responses during autoimmunity. Herein, we investigate the concept that the diversity of parasitifer sensitivity to commensal microbes and the specific constitution of the intestinal microbiota might impact host susceptibility to epilepsy through promotion of Th17 cell populations in the central nervous system (CNS).

scholarly journals Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders

2017 ◽  
Vol 2017 ◽  
pp. 1-25 ◽  
Author(s):  
Viviana I. Torres ◽  
Daniela Vallejo ◽  
Nibaldo C. Inestrosa
Keyword(s):  
Central Nervous System ◽  
Neurological Disorders ◽  
Neuronal Development ◽  
Protein Complexes ◽  
Synaptic Proteins ◽  
Excitatory Synapses ◽  
Complex Structures ◽  
Disease Phenotype ◽  
The Central Nervous System ◽  
Invertebrate Models

Synapses are complex structures that allow communication between neurons in the central nervous system. Studies conducted in vertebrate and invertebrate models have contributed to the knowledge of the function of synaptic proteins. The functional synapse requires numerous protein complexes with specialized functions that are regulated in space and time to allow synaptic plasticity. However, their interplay during neuronal development, learning, and memory is poorly understood. Accumulating evidence links synapse proteins to neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. In this review, we describe the way in which several proteins that participate in cell adhesion, scaffolding, exocytosis, and neurotransmitter reception from presynaptic and postsynaptic compartments, mainly from excitatory synapses, have been associated with several synaptopathies, and we relate their functions to the disease phenotype.

Intake of Anti-Epileptic Drugs and their Influences on Sexual Dysfunctions

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Roheela Yasmeen ◽  
Nida Mobeen ◽  
Muhammad Amjad Khan ◽  
Irfan Aslam ◽  
Samia Chaudhry
Keyword(s):  
Quality Of Life ◽  
Sexual Dysfunction ◽  
Neurological Disorders ◽  
Penile Erection ◽  
The Central Nervous System ◽  
Relationship Of ◽  
The Relationship ◽  
The Brain ◽  
Psychiatric Problems

Epilepsy which is also called seizures disorder is an uncontrolled action of the central nervous system. Itis not a single disease but a set of neurological disorders. Actually in this situation, the brain does notreceive a precise signal and as a result an abnormal condition is produced that is usually involuntary inaction. In this review, we aimed to focus on the relationship of anti-epileptic drugs with sexual dysfunctionand adaptation of better remedies that improve a patient’s family life. Sexual dysfunction is a commoncomorbidity in people with epilepsy which badly affects their quality of life. Sexual dysfunction is causedby different factors like psychiatric problems, anti-epileptic drugs (AEDs) and social factors etc. Sexualdysfunctions include ejaculatory failure, lessen libido, penile erection in men and irregular menstrual cyclein women. Common drugs such as Topiramate, Gabapentin (GBP), Valproate (VA), Carbamazepine (CBZ),Olanzapine (OL) and Risperidone (RTG) that are in practice to treat epilepsy usually produced adverseeffect on sexual dysfunction. Even though a lot of studies have been carried out to control sexualdysfunction in epilepsy’s patient, but still research is going on. Medicine such as Cyproheptadine,Mianserin, Buspirone, Yohimbine were found better to treat epilepsy with minimum side effects of sexualdysfunction. Moreover, it is also seen that certain vasodilators, folate , and vitamin supplements areeffective in improving the quality of life.

scholarly journals Congenital Central Hypoventilation Syndrome: A Comprehensive Review and Future Challenges

2014 ◽  
Vol 2014 ◽  
pp. 1-8
Author(s):  
Karin Ljubič ◽  
Iztok Fister ◽  
Iztok Fister
Keyword(s):  
Ventilatory Support ◽  
Congenital Central Hypoventilation Syndrome ◽  
Phox2b Gene ◽  
Central Controller ◽  
Future Challenges ◽  
The Central Nervous System ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome ◽  
Cardiovascular Functions

Congenital central hypoventilation syndrome is a disorder predisposed by a paired-like homebox PHOX2B gene. A mutation in the PHOX2B gene is a requisite when diagnosing congenital central hypoventilation syndrome. This mutation is identified in 93–100% of diagnosed patients. The mutation regarding this disorder affects the sensors, the central controller, and the integration of the signals within the central nervous system. This, inter alia, leads to insufficient ventilation and a decrease in PaO2, as well as an increase in PaCO2. Affected children are at risk during and after the neonatal period. They suffer from hypoventilation periods which may be present whilst sleeping only or in more severe cases when both asleep and awake. It is important for clinicians to perform an early diagnosis of congenital central hypoventilation in order to prevent the deleterious effects of hypoxaemia, hypercapnia, and acidosis on the neurocognitive and cardiovascular functions. Patients need long-term management and appropriate ventilatory support for improving the qualities of their lives. This paper provides a detailed review of congenital central hypoventilation syndrome, a congenital disorder that is genetic in origin. We describe the genetic basis, the wider clinical picture, and those challenges during the diagnosis and management of patients with this condition.

scholarly journals Insights Into the Role of CSF1R in the Central Nervous System and Neurological Disorders

2021 ◽  
Vol 13 ◽  
Author(s):  
Banglian Hu ◽  
Shengshun Duan ◽  
Ziwei Wang ◽  
Xin Li ◽  
Yuhang Zhou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Colony Stimulating Factor ◽  
Loss Of Function ◽  
Axonal Spheroids ◽  
The Central Nervous System ◽  
Stimulating Factor

The colony-stimulating factor 1 receptor (CSF1R) is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the central nervous system (CNS). CSF1R, which can be proteolytically cleaved into a soluble ectodomain and an intracellular protein fragment, supports the survival of myeloid cells upon activation by two ligands, colony stimulating factor 1 and interleukin 34. CSF1R loss-of-function mutations are the major cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its dysfunction has also been implicated in other neurodegenerative disorders including Alzheimer’s disease (AD). Here, we review the physiological functions of CSF1R in the CNS and its pathological effects in neurological disorders including ALSP, AD, frontotemporal dementia and multiple sclerosis. Understanding the pathophysiology of CSF1R is critical for developing targeted therapies for related neurological diseases.

scholarly journals Late developing cardiac lymphatic vasculature supports adult zebrafish heart function and regeneration

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Michael RM Harrison ◽  
Xidi Feng ◽  
Guqin Mo ◽  
Antonio Aguayo ◽  
Jessi Villafuerte ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Lymphatic System ◽  
Vascular System ◽  
Heart Function ◽  
Lymphatic Vessels ◽  
Adult Zebrafish ◽  
Heart Patients ◽  
Scar Size ◽  
Lymphatic Vasculature ◽  
Zebrafish Heart

The cardiac lymphatic vascular system and its potentially critical functions in heart patients have been largely underappreciated, in part due to a lack of experimentally accessible systems. We here demonstrate that cardiac lymphatic vessels develop in young adult zebrafish, using coronary arteries to guide their expansion down the ventricle. Mechanistically, we show that in cxcr4a mutants with defective coronary artery development, cardiac lymphatic vessels fail to expand onto the ventricle. In regenerating adult zebrafish hearts the lymphatic vasculature undergoes extensive lymphangiogenesis in response to a cryoinjury. A significant defect in reducing the scar size after cryoinjury is observed in zebrafish with impaired Vegfc/Vegfr3 signaling that fail to develop intact cardiac lymphatic vessels. These results suggest that the cardiac lymphatic system can influence the regenerative potential of the myocardium.

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