scholarly journals SIGLEC1 (CD169): a marker of active neuroinflammation in the brain but not in the blood of MS patients

2020 ◽  
Author(s):  
Lennard Ostendorf ◽  
Philipp Dittert ◽  
Robert Biesen ◽  
Ankelien Duchow ◽  
Victoria Stiglbauer ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Severe Disease ◽  
Myeloid Cells ◽  
Brain Lesions ◽  
Demyelinating Diseases ◽  
Interferon Treatment ◽  
Immunomodulatory Treatment ◽  
The Central Nervous System ◽  
Almost All ◽  
The Brain

AbstractObjectiveWe aimed to evaluate SIGLEC1 (CD169) as a biomarker in Multiple Sclerosis (MS) and Neuromyelitis optica spectrum disorder (NMOSD) and to evaluate the specificity of SIGLEC1+ myeloid cells for demyelinating diseasesMethodsWe performed flow cytometry-based measurements of SIGLEC1 expression on monocytes in 86 MS patients, 41 NMOSD patients and 31 healthy controls. Additionally, we histologically evaluated the presence of SIGLEC1+ myeloid cells in acute and chronic MS brain lesions as well as other neurological diseases.ResultsWe found elevated SIGLEC1 expression in 16/86 (18.6%) MS patients and 4/41 (9.8%) NMOSD patients. Almost all MS patients with high SIGLEC1 levels received exogenous interferon beta as an immunomodulatory treatment and only a small fraction of MS patients without interferon treatment had increased SIGLEC1 expression. SIGLEC1+ myeloid cells were abundantly present in active MS lesions as well as in a range of acute infectious and malignant diseases of the central nervous system, but not chronic MS lesions.ConclusionIn our cohort, SIGLEC1 expression on monocytes was – apart from those patients receiving interferon treatment – not significantly increased in patients with MS and NMOSD, nor were levels associated with more severe disease. The presence of SIGLEC1+ myeloid cells in brain lesions could be used to investigate the activity in an inflammatory CNS lesion.

scholarly journals SIGLEC1 (CD169): a marker of active neuroinflammation in the brain but not in the blood of multiple sclerosis patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lennard Ostendorf ◽  
Philipp Dittert ◽  
Robert Biesen ◽  
Ankelien Duchow ◽  
Victoria Stiglbauer ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Neurological Diseases ◽  
Severe Disease ◽  
Myeloid Cells ◽  
Brain Lesions ◽  
Demyelinating Diseases ◽  
Interferon Treatment ◽  
The Central Nervous System ◽  
Multiple Sclerosis Patients ◽  
Almost All

AbstractWe aimed to evaluate SIGLEC1 (CD169) as a biomarker in multiple sclerosis (MS) and Neuromyelitis optica spectrum disorder (NMOSD) and to evaluate the presence of SIGLEC1+ myeloid cells in demyelinating diseases. We performed flow cytometry-based measurements of SIGLEC1 expression on monocytes in 86 MS patients, 41 NMOSD patients and 31 healthy controls. Additionally, we histologically evaluated the presence of SIGLEC1+ myeloid cells in acute and chronic MS brain lesions as well as other neurological diseases. We found elevated SIGLEC1 expression in 16/86 (18.6%) MS patients and 4/41 (9.8%) NMOSD patients. Almost all MS patients with high SIGLEC1 levels received exogenous interferon beta as an immunomodulatory treatment and only a small fraction of MS patients without interferon treatment had increased SIGLEC1 expression. In our cohort, SIGLEC1 expression on monocytes was—apart from those patients receiving interferon treatment—not significantly increased in patients with MS and NMOSD, nor were levels associated with more severe disease. SIGLEC1+ myeloid cells were abundantly present in active MS lesions as well as in a range of acute infectious and malignant diseases of the central nervous system, but not chronic MS lesions. The presence of SIGLEC1+ myeloid cells in brain lesions could be used to investigate the activity in an inflammatory CNS lesion.

scholarly journals Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1929 ◽  
Author(s):  
Salman Ul Islam ◽  
Adeeb Shehzad ◽  
Muhammad Bilal Ahmed ◽  
Young Sup Lee
Keyword(s):  
Drug Delivery ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Nasal Delivery ◽  
Intranasal Route ◽  
Drug Molecules ◽  
Surface Enhanced ◽  
Effective Delivery ◽  
The Central Nervous System ◽  
The Brain

Although the global prevalence of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, glioblastoma, epilepsy, and multiple sclerosis is steadily increasing, effective delivery of drug molecules in therapeutic quantities to the central nervous system (CNS) is still lacking. The blood brain barrier (BBB) is the major obstacle for the entry of drugs into the brain, as it comprises a tight layer of endothelial cells surrounded by astrocyte foot processes that limit drugs’ entry. In recent times, intranasal drug delivery has emerged as a reliable method to bypass the BBB and treat neurological diseases. The intranasal route for drug delivery to the brain with both solution and particulate formulations has been demonstrated repeatedly in preclinical models, including in human trials. The key features determining the efficacy of drug delivery via the intranasal route include delivery to the olfactory area of the nares, a longer retention time at the nasal mucosal surface, enhanced penetration of the drugs through the nasal epithelia, and reduced drug metabolism in the nasal cavity. This review describes important neurological disorders, challenges in drug delivery to the disordered CNS, and new nasal delivery techniques designed to overcome these challenges and facilitate more efficient and targeted drug delivery. The potential for treatment possibilities with intranasal transfer of drugs will increase with the development of more effective formulations and delivery devices.

scholarly journals Aino Virus Antigen in Brain Lesions of a Naturally Aborted Bovine Fetus

1998 ◽  
Vol 35 (5) ◽  
pp. 409-411 ◽  
Author(s):  
Y. Noda ◽  
Y. Uchinuno ◽  
H. Shirakawa ◽  
S. Nagasue ◽  
N. Nagano ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Brain Lesion ◽  
Neutralizing Antibody ◽  
Virus Antigen ◽  
Brain Lesions ◽  
Significant Feature ◽  
The Central Nervous System ◽  
The Brain

A bovine fetus aborted at 187 days of gestation was serologically and immunohistopathologically examined. Serum and cerebrospinal fluid samples had high titers of virus-neutralizing antibody for Aino virus. A severe necrotizing encephalopathy was noted. Aino virus antigen was demonstrated in neuroglial cells within the brain lesion. The destruction of developing neuronal cells appeared to be a significant feature of the pathogenesis of lesions due to Aino virus infection in the central nervous system.

scholarly journals Effects of multiple sclerosis in pregnant and post-birth: particularities of the disease activity

2021 ◽  
Author(s):  
Bianca Barbosa Araldi ◽  
Victor Hugo Gomes ◽  
Bruno Ludvig Vieira ◽  
Klesia Adayani Rodrigues ◽  
Andressa Gabrieli da Silva ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Neurological Diseases ◽  
Neuroprotective Effect ◽  
Cumulative Effect ◽  
Demyelinating Diseases ◽  
Hormonal Changes ◽  
Neuroprotective Effects ◽  
Maternal Immune System ◽  
The Central Nervous System

Introduction: Demyelinating diseases are a heterogeneous group of neurological diseases related to autoimmunity whose representative is Multiple Sclerosis (MS). It is characterized by an immune-mediated demyelination of the central nervous system, with a typical outbreak and remission clinic. During pregnancy, a reduction in disease activity was noted due to immunomodulatory effects, and an increase in outbreaks in the puerperium. Thus, our goal is to demonstrate the relationship between pregnancy and MS. Methods: This is a systematic bibliographic review based on searching the SCIELO, PUBMED and UPTODATE databases using the words “Multiple Sclerosis”, “Pregnancy”, “Demyelinating diseases” and “Neurological Disorders”. Discussion: Pregnancy is responsible for numerous changes in the maternal body resulting from hormonal changes with an immunological and neuroprotective effect. Until the beginning of the 20th century, it was considered a risk factor or precipitator of outbreaks in these patients. In 1950, Tillmann et al. questioned him and concluded that pregnancy reduces the risk of outbreaks of the disease and that relapses were more associated with postpartum. The question is still raised by several authors, due to their interest in the search for intricate protective factors in the genesis and cure of the disease. It is believed that immunological changes in pregnancy tend to suppress the maternal immune system preventing fetal rejection, and together with gestational hormones, they are able to make neuronal tissue more resistant to inflammatory aggression and greater capacity for cell repair. In the puerperium, there was an increase in outbreaks of the disease, probably associated with a reduction in hormone levels, the effects of which are lost after the elimination of the fetus. Breastfeeding is not associated with the prevention or risk of new MS outbreaks. The frequency of outbreaks before conception is the only independent predictor of new post-term episodes. There is no consensus regarding the therapeutic approach in these pregnant women. Conclusion: Evidence supports the association between pregnancy, reduced activity of MS and increased activity in the 3 months postpartum, due to the probable loss of neuroprotective effects associated with hormones. Recommendations regarding the use of immunomodulator are suspended before conception (“washout”) until term. New evidence did not associate the use of interferon-β with abortion, cesarean section or low birth weight. There was a benefit of long-term parity with a cumulative effect on the patient’s immunohumor modulation.

scholarly journals Chronological brain lesions after SARS-CoV-2 infection in hACE2-transgenic mice

2021 ◽  
pp. 030098582110668
Author(s):  
Enric Vidal ◽  
Carlos López-Figueroa ◽  
Jordi Rodon ◽  
Mónica Pérez ◽  
Marco Brustolin ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Neuronal Damage ◽  
Brain Lesions ◽  
Olfactory Mucosa ◽  
Histopathological Analysis ◽  
Post Inoculation ◽  
Vacuolar Degeneration ◽  
Early Entry ◽  
The Central Nervous System ◽  
The Brain

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease, but it can also affect other organs including the central nervous system. Several animal models have been developed to address different key questions related to Coronavirus Disease 2019 (COVID-19). Wild-type mice are minimally susceptible to certain SARS-CoV-2 lineages (beta and gamma variants), whereas hACE2-transgenic mice succumb to SARS-CoV-2 and develop a fatal neurological disease. In this article, we aimed to chronologically characterize SARS-CoV-2 neuroinvasion and neuropathology. Necropsies were performed at different time points, and the brain and olfactory mucosa were processed for histopathological analysis. SARS-CoV-2 virological assays including immunohistochemistry were performed along with a panel of antibodies to assess neuroinflammation. At 6 to 7 days post inoculation (dpi), brain lesions were characterized by nonsuppurative meningoencephalitis and diffuse astrogliosis and microgliosis. Vasculitis and thrombosis were also present and associated with occasional microhemorrhages and spongiosis. Moreover, there was vacuolar degeneration of virus-infected neurons. At 2 dpi, SARS-CoV-2 immunolabeling was only found in the olfactory mucosa, but at 4 dpi intraneuronal virus immunolabeling had already reached most of the brain areas. Maximal distribution of the virus was observed throughout the brain at 6 to 7 dpi except for the cerebellum, which was mostly spared. Our results suggest an early entry of the virus through the olfactory mucosa and a rapid interneuronal spread of the virus leading to acute encephalitis and neuronal damage in this mouse model.

Myeloid cells: The Trojan horse for T cell invasion into the brain

2019 ◽  
Vol 11 (520) ◽  
pp. eaaz9757
Author(s):  
Gilbert Gallardo
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Cell Invasion ◽  
Myeloid Cells ◽  
Autoimmune Encephalomyelitis ◽  
Lectin Receptors ◽  
The Central Nervous System ◽  
The Brain ◽  
Experimental Autoimmune

C-type lectin receptors on myeloid cells regulate the activation and infiltration of T cells into the central nervous system in experimental autoimmune encephalomyelitis.

scholarly journals Immovable Object Meets Unstoppable Force? Dialogue Between Resident and Peripheral Myeloid Cells in the Inflamed Brain

2020 ◽  
Vol 11 ◽  
Author(s):  
Alanna G. Spiteri ◽  
Claire L. Wishart ◽  
Nicholas J. C. King
Keyword(s):  
Myeloid Cells ◽  
Cell Types ◽  
Brain Parenchyma ◽  
Specific Cell ◽  
Novel Treatments ◽  
Experimental Systems ◽  
Immune Mediated ◽  
Recent Developments ◽  
The Central Nervous System ◽  
The Brain

Inflammation of the brain parenchyma is characteristic of neurodegenerative, autoimmune, and neuroinflammatory diseases. During this process, microglia, which populate the embryonic brain and become a permanent sentinel myeloid population, are inexorably joined by peripherally derived monocytes, recruited by the central nervous system. These cells can quickly adopt a morphology and immunophenotype similar to microglia. Both microglia and monocytes have been implicated in inducing, enhancing, and/or maintaining immune-mediated pathology and thus disease progression in a number of neuropathologies. For many years, experimental and analytical systems have failed to differentiate resident microglia from peripherally derived myeloid cells accurately. This has impeded our understanding of their precise functions in, and contributions to, these diseases, and hampered the development of novel treatments that could target specific cell subsets. Over the past decade, microglia have been investigated more intensively in the context of neuroimmunological research, fostering the development of more precise experimental systems. In light of our rapidly growing understanding of these cells, we discuss the differential origins of microglia and peripherally derived myeloid cells in the inflamed brain, with an analysis of the problems resolving these cell types phenotypically and morphologically, and highlight recent developments enabling more precise identification.

scholarly journals Systemic Delivery of Tyrosine-Mutant AAV Vectors Results in Robust Transduction of Neurons in Adult Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Asako Iida ◽  
Naomi Takino ◽  
Hitomi Miyauchi ◽  
Kuniko Shimazaki ◽  
Shin-ichi Muramatsu
Keyword(s):  
Transgene Expression ◽  
Neurological Diseases ◽  
Systemic Delivery ◽  
Adeno Associated Virus ◽  
Gene Therapies ◽  
Adult Mice ◽  
The Central Nervous System ◽  
Foreign Dna ◽  
The Brain ◽  
Limited Usefulness

Recombinant adeno-associated virus (AAV) vectors are powerful tools for both basic neuroscience experiments and clinical gene therapies for neurological diseases. Intravascularly administered self-complementary AAV9 vectors can cross the blood-brain barrier. However, AAV9 vectors are of limited usefulness because they mainly transduce astrocytes in adult animal brains and have restrictions on foreign DNA package sizes. In this study, we show that intracardiac injections of tyrosine-mutant pseudotype AAV9/3 vectors resulted in extensive and widespread transgene expression in the brains and spinal cords of adult mice. Furthermore, the usage of neuron-specific promoters achieved selective transduction of neurons. These results suggest that tyrosine-mutant AAV9/3 vectors may be effective vehicles for delivery of therapeutic genes, including miRNAs, into the brain and for treating diseases that affect broad areas of the central nervous system.

scholarly journals The Pain System in Oesophageal Disorders: Mechanisms, Clinical Characteristics, and Treatment

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Christian Lottrup ◽  
Søren Schou Olesen ◽  
Asbjørn Mohr Drewes
Keyword(s):  
Severe Disease ◽  
Treatment Options ◽  
Primary Treatment ◽  
Lifestyle Changes ◽  
Sensory Receptors ◽  
Pain Mechanisms ◽  
Afferent Nerves ◽  
The Central Nervous System ◽  
The Brain

Pain is common in gastroenterology. This review aims at giving an overview of pain mechanisms, clinical features, and treatment options in oesophageal disorders. The oesophagus has sensory receptors specific for different stimuli. Painful stimuli are encoded by nociceptors and communicated via afferent nerves to the central nervous system. The pain stimulus is further processed and modulated in specific pain centres in the brain, which may undergo plastic alterations. Hence, tissue inflammation and long-term exposure to pain can cause sensitisation and hypersensitivity. Oesophageal sensitivity can be evaluated ,for example, with the oesophageal multimodal probe. Treatment should target the cause of the patient's symptoms. In gastro-oesophageal reflux diseases, proton pump inhibitors are the primary treatment option, surgery being reserved for patients with severe disease resistant to drug therapy. Functional oesophageal disorders are treated with analgesics, antidepressants, and psychological therapy. Lifestyle changes are another option with less documentation.

Effects of Neuroinflammation on Neural Stem Cells

2016 ◽  
Vol 23 (1) ◽  
pp. 27-39 ◽  
Author(s):  
Ruxandra Covacu ◽  
Lou Brundin
Keyword(s):  
Immune Responses ◽  
Subventricular Zone ◽  
Neurological Diseases ◽  
Experimental Models ◽  
Adaptive Immune ◽  
Neural Stem Progenitor Cells ◽  
The Central Nervous System ◽  
And Migration ◽  
The Brain ◽  
Proliferation And Migration

Neural stem/progenitor cells (NSCs/NPCs) are present in different locations in the central nervous system. In the subgranular zone (SGZ) there is a constant generation of new neurons under normal conditions. New neurons are also formed from the subventricular zone (SVZ) NSCs, and they migrate anteriorly as neuroblast to the olfactory bulb in rodents, whereas in humans migration is directed toward striatum. Most CNS injuries elicit proliferation and migration of the NSCs toward the injury site, indicating the activation of a regenerative response. However, regeneration from NSC is incomplete, and this could be due to detrimental cues encountered during inflammation. Different CNS diseases and trauma cause activation of the innate and adaptive immune responses that influence the NSCs. Furthermore, NSCs in the brain react differently to inflammatory cues than their counterparts in the spinal cord. In this review, we have summarized the effects of inflammation on NSCs in relation to their origin and briefly described the NSC activity during different neurological diseases or experimental models.

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