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Блокада канала натрия Флекаинида повышает целостность мозгового барьера и способствует нейрозащите при нейроинфламмации.

Множественный склероз (MS), аутоиммунный расстройство, характеризуется сильным нейроинфламмированием, приводящим к обезвоживанию и нейронным повреждениям в CNS, что приводит к значительным клиническим расстройствам. Подвижки MS связаны со сложными патологическими процессами, такими как вторжение в иммунные клетки и набор на службу в ЦНС с помощью цитокина. Экспериментальный аутоиммунный энцефаломиэлит (EAE), широко используемый в качестве модели для MS, несмотря на его ограничения в плане перевода, имеет решающее значение для выявления эффективных методов лечения. Недавние исследования показал

Совпадение в аннотации оригинала
Multiple Sclerosis (MS), an autoimmune disorder, is characterized by severe neuroinflammation, leading to demyelination and neuronal damage … ses like immune cell invasion and cytokine-mediated recruitment to the CNS. Experimental autoimmune encephalomyelitis (EAE), widely used as a model for MS, despite its translational limitations, has been crucial for identifying effective treatments. Recent studies have shown that sodium channel (NaV) blockers and monoamine oxidase- (MAO) B inhibitors can alleviate …

Reprogramming autoimmunity: inducing antigen-specific tolerance via apoptotic mimicry in an experimental model of multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disorder characterized by demyelination, axonal damage, and neurodegeneration, lea … ligodendrocyte glycoprotein (MOG35 - 55) peptide] in the MOG35 - 55-induced experimental autoimmune encephalomyelitis (EAE), as a therapeutic strategy for the treatment of MS. METHODS: MOG PS liposomes or empty PS liposomes were administered in a single administration before or after the appearance of EAE neurological symptoms. Intraperitoneal, intranasal, intrade …

На экране Vivo CRISPR показано регулирование макрофажных состояний в нейроинфламмации.

Здесь мы создали скрининговый трубопровод в vivo CRISPR с использованием генетически отредактируемых клеток потомков для регулирования макрофага в мышиных моделях множественного склероза (MS). Скрининг более 100 цитокиновых рецепторов и сигнальных молекул выявила интерферон-Калайоки, некроз опухоли, гранулоцит-макропадажный фактор-стимулирующий фактор и преобразование фактора роста-β в основные регуляторы поляризации макрофага в vivo. Одноклеточная транскриптомика подтвердила, что перенесенные потомственные клетки генерируют все популяции миелиоидных клеток CNS, что позволяет проводить анализ

Mesoporous polydopamine nanoparticle-based tolerogenic vaccine induces antigen-specific immune tolerance to prevent and treat autoimmune multiple sclerosis.

Multiple sclerosis (MS) is a chronic neurological disorder derived from autoreactive immune system attacking the protective myelin sheath that surrounds nerves in the central nervous system (CNS). Here, a tolerogenic nanovaccine for generating an antigen-specific immune tolerance for treating MS is proposed. It consisted of a mesoporous polydopamine (mPDA) nanoparticle, characterized by high reactive oxygen species (ROS)-scavenging property, loaded with MS-derived autoantigen. Intravenous vaccination of autoantigen-loaded mPDA could induce tolerogenic dendritic cells (DCs) with low expression

Astrocyte-derived factors regulate CNS myelination.

The role that astrocytes play in central nervous system (CNS) myelination is poorly understood. We investigated the contribution of astrocyte-derived factors to myelination and revealed a substantial overlap in the secretomes of human and rat astrocytes. Using in vitro myelinating co-cultures of primary retinal ganglion cells and cortical oligodendrocyte precursor cells, we discovered that factors secreted by resting astrocytes, but not reactive astrocytes, facilitated myelination. Soluble brevican emerged as a new enhancer of developmental myelination in vivo, CNS and its absence was linked t

The mitochondriogenic but not the immunosuppressant effects of mTOR inhibitors prompt neuroprotection and delay disease evolution in a mouse model of progressive multiple sclerosis.

INTRODUCTION: Purportedly, the progression of multiple sclerosis (MS) occurs when neurodegenerative processes due to derangement of axonal bioenergetics take over the autoimmune response. However, a clear picture of the causative interrelationship between autoimmunity and axonal mitochondrial dysfunction in progressive MS (PMS) pathogenesis waits to be provided. METHODS: In the present study, by adopting the NOD mouse model of PMS, we compared the pharmacological effects of the immunosuppressants dexamethasone and fingolimod with those of mTOR inhibitors rapamycin and everolimus that, in addi

Venezuelan equine encephalitis virus E1 protein interacts with PDIA6 and PDI inhibition reduces alphavirus production.

Venezuelan equine encephalitis virus (VEEV) is an alphavirus transmitted by mosquitos that can cause a febrile illness and induce severe neurological complications in humans and equine populations. Currently there are no FDA approved vaccines or antiviral treatments to combat VEEV. Proteomic techniques were utilized to create an interactome of the E1 fusion glycoprotein of VEEV. VEEV E1 interacted with a number of cellular chaperone proteins including protein disulfide isomerase family A member 6 (PDIA6). PDI inhibition through LOC14 and/or nitazoxanide treatment effectively decreased producti

Vitamin D increases glucocorticoid efficacy via inhibition of mTORC1 in experimental models of multiple sclerosis.

The limited efficacy of glucocorticoids (GCs) during therapy of acute relapses in multiple sclerosis (MS) leads to long-term disability. We investigated the potential of vitamin D (VD) to enhance GC efficacy and the mechanisms underlying this VD/GC interaction. In vitro, GC receptor (GR) expression levels were quantified by ELISA and induction of T cell apoptosis served as a functional readout to assess synergistic 1,25(OH)2D3 (1,25D)/GC effects. Experimental autoimmune encephalomyelitis (MOG35-55 EAE) was induced in mice with T cell-specific GR or mTORc1 deficiency. 25(OH)D (25D) levels were …

[11C]PIB PET imaging can detect white and grey matter demyelination in a non-human primate model of progressive multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system. Its diagnosis is clinical, of … ite and grey matter of non-human primate model of progressive MS. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in marmosets by injection of recombinant human myelin oligodendrocyte glycoprotein (rhMOG) emulsified in either Incomplete Freund's Adjuvant (IFA) or Complete Freund's Adjuvant (CFA). [11C]PIB PET images were acquired prior to immu …

Epidemiology of paraneoplastic neurological syndromes: a population-based study.

BACKGROUND: The epidemiology of paraneoplastic neurological syndromes (PNS) remains to be defined. We present here the first population-base … 4.37 per 100,000. Most common PNS were limbic encephalitis (31%), cerebellar degeneration (28%) and encephalomyelitis (20%). Among antibody (Ab)-positive cases, most frequent specificities included: Yo (30%), Hu (26%), and Ma2 (22%), while the most frequent associated tumors were lung (17%) and breast cancer (16%), followed by lymphoma (12%). PNS developed in 1 in …

Complex Epidemiological Dynamics of Eastern Equine Encephalitis Virus in Florida.

Eastern equine encephalitis virus (EEEV) infection results in high mortality in infected horses and humans. Florida has been identified as an important source of EEEV epidemics to other states in the United States. In this study, we further characterized the epidemiological and evolutionary dynamics of EEEV in Florida. Epidemiological analysis of sentinel chicken seroconversion rates to EEEV infections during 2005-2016 suggested significant seasonality of EEEV activity in Florida. We observed significant annual activity of EEEV in the North and North Central regions, with little significant se

Clinical presentation, diagnostic findings and outcome in dogs diagnosed withpresumptive spinal-only meningoen-cephalomyelitis of unknown origin.

OBJECTIVES: To summarise clinical presentation, diagnostic findings and long-term outcome for dogs clinically diagnosed with meningoencephalomyelitis of unknown origin affecting the spinal cord alone. METHODS: Medical records were reviewed for dogs diagnosed with presumptive spinal-only meningoencephalomyelitis of unknown origin between 2006 and 2015. RESULTS: 21 dogs were included; the majority presented with an acute (43%) or chronic (52%) onset of neurological signs. Ambulatory paresis was the most common neurological presentation (67%). Neurological examination most commonly revealed a T…

Nationwide Incidence of Acquired Central Nervous System Demyelination in Icelandic Children.

INTRODUCTION: Recognizing acquired demyelinating syndromes and multiple sclerosis is important to commence early treatment. The objective of … een patients were initially diagnosed with clinically isolated syndrome, two had acute disseminated encephalomyelitis, two had multiple sclerosis, and one had neuromyelitis optica. Seven children were diagnosed with multiple sclerosis; three patients with clinically isolated syndrome developed multiple sclerosis after the age of 18 and were not included in the mult …

Role of angiotensin II in experimental Venezuelan equine encephalitis in rats.

Venezuelan equine encephalitis (VEE) is a viral disease transmitted by mosquitoes. The inflammation induced by the VEE virus is associated with a high mortality rate in mice. Angiotensin II (Ang II), a pro-inflammatory molecule, is produced in the normal rat brain. There is no information about the role of this molecule in the inflammatory events occurring during VEE and the effect of inflammation on the mortality rate in VEE-virus-infected rats. This study was designed to determine the role of Ang II in VEE and to analyze the effect of inflammation on mortality in infected rats. Two groups of

Aminoguanidine and N-acetyl-cysteine supress oxidative and nitrosative stress in EAE rat brains.

Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of human multiple sclerosis (MS). We have evaluated the role of oxidative and nitrosative stress, as the causal factors in the development of EAE, responsible for the damage of cardinal cellular components, such as lipids, proteins and nucleic acids, resulting in demyelination, axonal damage, and neuronal death. EAE was induced in female Sprague-Dawley rats, 3 months old (300±20 g), by immunization with myelin basic protein in combination with Complete Freund's adjuvant (CFA). The animals were divided into seven…

The role of the blood-brain barrier during Venezuelan equine encephalitis virus infection.

Venezuelan equine encephalitis (VEE) virus is a mosquito-borne alphavirus associated with sporadic outbreaks in human and equid populations in the Western Hemisphere. After the bite of an infected mosquito, the virus initiates a biphasic disease: a peripheral phase with viral replication in lymphoid and myeloid tissues, followed by a neurotropic phase with infection of central nervous system (CNS) neurons, causing neuropathology and in some cases fatal encephalitis. The mechanisms allowing VEE virus to enter the CNS are currently poorly understood. Previous data have shown that the virus gains

Differential accumulation of genetic and phenotypic changes in Venezuelan equine encephalitis virus and Japanese encephalitis virus following passage in vitro and in vivo.

The requirement to replicate in both vertebrate and invertebrate hosts is thought to limit the introduction of genetic changes into the genome of arboviruses. Serial passage under laboratory conditions will overcome this limitation allowing for genetic changes to be introduced and affecting the virulence of the virus for animals. In the studies detailed here, the consequence of removing the restriction of alternate replication was demonstrated to be different depending on the virus. Passing Venezuelan equine encephalitis virus in tissue culture cells, eggs or mice resulted in up to 11 nucleoti

Imaging evaluation of demyelinating processes of the central nervous system.

Demyelinating processes involving the central nervous system have a variety of aetiologies and can be separated into primary and secondary demyelinating processes. The classic example of primary demyelination is multiple sclerosis. Secondary demyelination, where the aetiology is known, includes infectious, metabolic and toxic disease processes. The underlying component of all demyelinating disorders is damage to the myelin sheath and/or the oligodendrocyte, the cell forming the myelin sheath. These processes often have similar imaging findings, making knowledge of the patient's history, physic

REVIEW PAPER: pathology of animal models of alphavirus encephalitis.

The encephalitides caused by Venezuelan (VEEV), eastern (EEEV), and western (WEEV) equine encephalitis viruses are important natural diseases of horses and humans and potential agents of biowarfare or bioterrorism. No licensed vaccines or specific therapies exist to prevent or treat human infections with VEEV, EEEV, or WEEV. Well-characterized animal models are needed to support the development of such medical countermeasures under the United States Food and Drug Administration's "Animal Rule." This review focuses on the pathological features and pathogenetic mechanisms of these alphaviral enc