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TSPO PET в множестве склерозов: новые знания в патофизиологии, прогнозе и мониторинге лечения.

Множественный склероз (MS) — хроническое аутоиммунное заболевание центральной нервной системы (CNS), характеризующееся воспалением, обезвоживанием и нейродегенерацией. Белок транслокатора 18 кДа (TSPO) перевыражается на активированном микроглии, ключевом посреднике острой и хронической воспаления в MS. Позитронная томография выбросов (PET), ориентированная на TSPO, позволяет вживо обнаруживать микроглиальную активацию в MS, выявляя высокую долю повреждений активных белых веществ (WM). Она также обнаруживает значительную врожденную иммунную активацию в обычно встречающемся белом веществе (NAWM)

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination and neurodegeneration. The 18 kDa translocator protein (TSPO) is overexpressed on activated microglia, a key mediator of acute and chronic inflammation in MS. Positron emission tomography (PET) targeting TSPO enables in viv…

A lymphocyte-microglia-astrocyte axis in chronic active multiple sclerosis.

Multiple sclerosis (MS) lesions that do not resolve in the months after they form harbour ongoing demyelination and axon degeneration, and are identifiable in vivo by their paramagnetic rims on MRI scans1-3. Here, to define mechanisms underlying this disabling, progressive neurodegenerative state4-6 and foster development of new therapeutic agents, we used MRI-informed single-nucleus RNA sequencing to profile the edge of demyelinated white matter lesions at various stages of inflammation. We uncovered notable glial and immune cell diversity, especially at the chronically inflamed lesion edge. …

Immune reconstitution inflammatory syndrome and the central nervous system.

PURPOSE OF REVIEW: Central nervous system-immune reconstitution inflammatory syndrome (CNS-IRIS) is a recently recognized, devastating, T-cell-mediated encephalitis that occurs in the setting of treatment of HIV infection or autoimmune diseases, the management of which remains challenging. We review the pathophysiology, the clinical subtypes and present guidelines for prevention, diagnosis and treatment of this entity. RECENT FINDINGS: Nearly all patients with multiple sclerosis who develop progressive multifocal leukoencephalopathy (PML) following treatment with natalizumab develop IRIS whic…

Груенберг Ганльон: Неисследованный объект для доставки внутриутробных наркотиков в болезни Альцгеймера.

Неврологические расстройства, такие как болезнь Альцгеймера, болезнь Паркинсона, болезнь Хантингтона, множественный склероз и амиотропический боковой склероз, создают серьезные проблемы для лечения. К числу причин, по которым трудно найти средства для лечения этих заболеваний, относятся осложнения при ранней диагностике, прогрессивные и необратимые нейронные повреждения и наличие кровеносного барьера (ББД), который препятствует доставке лекарств в затронутые районы мозга. Управление лекарствами внутриутробного характера (ИНЛ) все больше пользуется популярностью среди исследователей за то, что

Совпадение в аннотации оригинала
Neurological disorders such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis pose significant challenges for treatment. Reasons for the difficulty in finding cures for these conditions include complications in early diagnosis, progressive and irreversible neuronal damage, and the presenc…

The potential use of tetracyclines in neurodegenerative diseases and the role of nano-based drug delivery systems.

Neurodegenerative diseases are still a challenge for effective treatments. The high cost of approved drugs, severity of side effects, inject … dels of neurodegenerative diseases. In clinical studies, satisfactory results have been obtained in Multiple sclerosis (MS) but not yet in other disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), or Amyotrophic lateral sclerosis (ALS). In recent years, researchers have developed and evaluated nanoparticulate drug delivery systems to improve the cl …

Calcium Permeable-AMPA Receptors and Excitotoxicity in Neurological Disorders.

Excitotoxicity is one of the primary mechanisms of cell loss in a variety of diseases of the central and peripheral nervous systems. Other than the previously established signaling pathways of excitotoxicity, which depend on the excessive release of glutamate from axon terminals or over-activation of NMDA receptors (NMDARs), Ca2+ influx-triggered excitotoxicity through Ca2+-permeable (CP)-AMPA receptors (AMPARs) is detected in multiple disease models. In this review, both acute brain insults (e.g., brain trauma or spinal cord injury, ischemia) and chronic neurological disorders, including Epil

Small molecular therapeutic targets for neurodegenerative diseases.

Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis disease are characterized by progressive neuronal loss, protein aggregation, and synaptic dysfunction. These diseases share common pathological mechanisms including oxidative stress, mitochondrial impairment, chronic neuroinflammation, protein misfolding, and epigenetic dysregulation. Current therapies offer only symptomatic relief and fail to halt disease progression. Recent advances in transcriptomics and proteomics have enabled the identification of shared molecular pathways and drug

Modulation of miR-145 in a mouse model of multiple sclerosis: A promising approach to attenuate inflammation and degeneration.

Multiple sclerosis (MS) is a progressive inflammatory disease of the central nervous system (CNS) marked by myelin loss, which impairs nerve function. Current therapies fail to halt disease progression or prevent myelin and axonal degeneration. In this study, we explored the impact of miR-145 loss in a murine model of experimental autoimmune encephalomyelitis (EAE), which mimics MS pathology. Loss of miR-145 reduced clinical severity and significantly decreased immune cell infiltration in the lumbar spinal cord during both the onset and chronic stages of the disease. Additionally, miR-145 loss…

Multiple sclerosis.

Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system in young adults. This disorder is a heterogeneous, multifactorial, immune-mediated disease that is influenced by both genetic and environmental factors. In most patients, reversible episodes of neurological dysfunction lasting several days or weeks characterize the initial stages of the disease (that is, clinically isolated syndrome and relapsing-remitting MS). Over time, irreversible clinical and cognitive deficits develop. A minority of patients have a pr…

[The biomarker and treatment in Hashimoto's encephalopahty].

Hashimoto's encephalopathy (HE) is a treatable disease based on autoimmune mechanisms associated with Hashimoto's thyroiditis. We recently discovered the serum autoantibodies (Abs) against the NH2-terminal of alpha-enolase (NAE) as a diagnostic biomarker for HE. The serum anti-NAE Abs are not detected in normal individuals and other disorders such as infections, collagen diseases, multiple sclerosis and other autoimmune conditions. The specificity of the serum anti-NAE Abs is 91% for HE whereas the sensitivity is 50%. In our clinical study of 80 cases of HE with anti-NAE Abs, the acute encepha…

Activation of calpain and caspase pathways in demyelination and neurodegeneration in animal model of multiple sclerosis.

Experimental autoimmune encephalomyelitis (EAE), a widely recognized animal model of multiple sclerosis (MS), is highly useful for studying inflammation, demyelination, and neurodegeneration in the central nervous system (CNS). EAE exhibits many similarities with MS, which is a chronic inflammatory disease affecting CNS white matter in humans. Various studies have indicated that EAE is a particularly useful animal model for understanding both the mechanisms of immune-mediated CNS pathology and also the progressive clinical course of MS. Demyelination and axonal dysfunction have previously been…

Multiple sclerosis: improvement of visuoperceptive functions by picoTesla range magnetic fields.

The occurrence of cognitive deficits in multiple sclerosis (MS) has been recognized since 1877 when Charcot first observed "enfeeblement of memory" in his patients. Recent studies employing standardized neuropsychological tests have confirmed the high incidence of cognitive deficits in MS patients particularly those with a chronic progressive course of the disease. Visuoperceptive and visuomotor deficits commonly occur in MS patients and are thought to reflect damage to attentional systems due to interruption by demyelinating plaques of nerve conduction along the ascending projections from the…

Magnetic fields normalize visual evoked potentials and brainstem auditory evoked potentials in multiple sclerosis.

The present communication concerns a 46 year old woman with a 10 year history of chronic progressive multiple sclerosis (MS) in whom external application of magnetic fields (MF) (7.5 picoTesla; 5 Hz) during a period of remission resulted in a rapid and dramatic improvement in symptoms including vision, cerebellar symptomatology (ataxia and dysarthria), mood, sleep, bowel and bladder functions as well as fatigue. Improvement in the patient's symptoms was associated with normalization of the pretreatment latencies of the visual evoked potentials and brainstem auditory evoked potential responses …

T and B lymphocytes in the cerebrospinal fluid of various neurological diseases.

Cerebrospinal fluids (CSF) from 66 patients with a variety of neurological disorders were studied for total protein content, absolute amount … imilar changes were also found in optic neuritis. The percentage of T cells was higher in relapsing multiple sclerosis than in the chronic progressive form. There were less striking changes in the B cell to T cell ratios in the CSF of other inflammatory diseases of the CNS.

Early Prognostic Factors in Multiple Sclerosis: Clinical and Therapeutic Implications.

Introduction: Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system with a highly heterogeneous clinical course. Early identification of patients at risk of aggressive disease progression is crucial for optimizing therapeutic strategies, including eligibility for highly effective treatments. Objective: The aim of this review was to synthesize current data on prognostic factors in multiple sclerosis, with particular emphasis on their significance in the early stages of the disease and potential clinical implications. Methods: A narrative systema…

In situ generation of EBNA1 CAR-T cells eradicates antigen specific auto-immune B cells for multiple sclerosis treatment.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Epstein‒Barr virus (EBV)-induced B-cell overactivation could lead to inflammatory injury to the CNS, which is thought to underlie the initiation and progression of MS. To specifically eradicate these B cells, we report in situ EBNA1-specific chimeric antigen receptor (CAR)-T cells that were transiently programmed with circular RNA (circRNA)-laden CD7-targeted lipid nanoparticles (CD7-LNP). We demonstrate that systematic injection of CD7-LNP can efficiently introduce CAR circRNA to T lym…

Связанные с прогрессом результаты терифлуномида в многочисленных склерозовых клинических испытаниях.

ВСТУПЛЕНИЕ: Множественный склероз (MS) является хроническим воспалительным заболеванием центральной нервной системы, которое приводит к неврологической неполноценности, более заметной в прогрессивной фазе. Терифлюномид — перорально-модифицирующая терапия — продемонстрировал потенциальные нейрозащитные эффекты, помимо сокращения рецидивов, включая сохранение целостности мозга и смягчение развития инвалидности. В настоящем обзоре приводятся подтверждающие данные о воздействии терифлюномида на развитие инвалидности, когнитивные и МРТ-маркеры нейродегенерации в MS.В целях выявления соответствующих

Совпадение в аннотации оригинала
INTRODUCTION: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that leads to neurological disability, more pronounced in the progressive phase. Teriflunomide, an oral disease-modifying therapy, has shown potential neuroprotective effects beyond relapse reduction, including preservation of brain integrity and mitigation …

Relationship between chronic demyelination of the optic nerve and short term axonal loss.

BACKGROUND: Axonal loss is a major determinant of disability in multiple sclerosis (MS). While acute inflammatory demyelination is a principal cause of axonal transection and subsequent axonal degeneration in acute disease, the nature of chronic axonal loss is less well understood. In the current study, the relationship between degree of chronic demyelination and axonal degeneration was investigated using optic neuritis (ON) as a model. METHOD: 25 patients with a first episode of unilateral ON, good recovery of visual function and concurrent brain or spinal cord MRI lesions were enrolled. Axo…

Astrocytes in Multiple Sclerosis: Getting to the Core.

Astrocytes are increasingly recognized as key regulators of multiple sclerosis (MS) pathogenesis, known to actively influence neuroinflammation, blood-brain barrier integrity, leukocyte recruitment, glial scar formation, and tissue repair. Evidence from both MS and its animal models demonstrates substantial astrocyte heterogeneity, exerting either pathogenic or neuroprotective functions depending on the local microenvironment. In this review, we discuss the diverse roles of astrocytes in MS, with particular focus on signaling pathways that govern astrocyte responses during chronic neuroinflamm…

Systemic administration of anti-CD20 indirectly reduces B cells in the inflamed meninges in a chronic model of central nervous system autoimmunity.

Anti-CD20 B cell depleting therapies have demonstrated that B cells are important drivers of disease progress in Multiple Sclerosis, although the pathogenic mechanisms are not well understood. A population of B cells accumulates in the inflamed meninges in MS and also some chronic animal models of disease, typically adjacent to demyelinating lesions. The role of these meningeal B cells in disease is not known, nor is their susceptibility to anti-CD20 therapy. Here, we administered anti-CD20 to 2D2 IgHMOG spontaneous experimental autoimmune encephalomyelitis mice in the chronic phase of disease…