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Deleterious role of IFNgamma in a toxic model of central nervous system demyelination.

Interferon-gamma (IFNgamma) is a pleiotropic cytokine that plays an important role in many inflammatory processes, including autoimmune diseases such as multiple sclerosis (MS). Demyelination is a hallmark of MS and a prominent pathological feature of several other inflammatory diseases of the central nervous system, including experimental autoimmune encephalomyelitis, an animal model of MS. Accordingly, in this study we followed the effect of IFNgamma in the demyelination and remyelination process by using an experimental autoimmune encephalomyelitis model of demyelination/remyelination after…

The poor recovery of neuromyelitis optica spectrum disorder is associated with a lower level of CXCL12 in the human brain.

Neuromyelitis optica spectrum disorders (NMOSDs) are blindness-causing neuritis. In NMOSD patients, NMO-IgG evokes astrocytopathy that in turn causes demyelination. While measurement of NMO-IgG titer will help neurologists make the diagnosis of NMOSDs, it is not sufficient to evaluate the severity of astrocytopathy. In this study, we compared the different levels of an astrocyte biomarker in cerebrospinal fluid of NMOSD patients with good or poor recovery, and then linked their differences to the changes in remyelinating promoter (CXCL12) levels. Our results indicate that NMO-IgG down-regulate

Changes of CXCL12, CXCL14 and PDGF levels in the brain of patients with idiopathic demyelinating optic neuritis and neuromyelitis optica.

The CXC chemokines (CXC-motif ligand 12 and CXC-motif ligand 14) and platelet-derived growth factor are suggested to modulate remyelination in the course of many demyelinating diseases. The present study compared the difference in the brain levels of these chemokines between patients with idiopathic demyelinating optic neuritis (IDON) and neuromyelitis optica (NMO) by measuring their concentrations in the cerebrospinal fluid using an enzyme linked immunosorbent assay. Our data indicate that the prognosis of neuritis depends on the remyelinating process that is impaired due to decreased chemoki…

Thyroid hormone-dependent oligodendroglial cell lineage genomic and non-genomic signaling through integrin receptors.

Multiple sclerosis (MS) is a heterogeneous autoimmune disease whereby the pathological sequelae evolve from oligodendrocytes (OLs) within the central nervous system and are targeted by the immune system, which causes widespread white matter pathology and results in neuronal dysfunction and neurological impairment. The progression of this disease is facilitated by a failure in remyelination following chronic demyelination. One mediator of remyelination is thyroid hormone (TH), whose reliance on monocarboxylate transporter 8 (MCT8) was recently defined. MCT8 facilitates the entry of THs into oli…

Astrocyte TNFR2 is required for CXCL12-mediated regulation of oligodendrocyte progenitor proliferation and differentiation within the adult CNS.

Multiple sclerosis (MS) is characterized by episodes of inflammatory demyelination with progressive failure of remyelination. Prior studies using murine models of MS indicate that remyelination within the adult central nervous system (CNS) requires the expression and activity of TNFR2 and CXCR4 by oligodendrocyte progenitor cells (OPCs), promoting their proliferation and differentiation into mature oligodendrocytes. Here, we extend these studies by examining the role of TNFR2 in the expression of the CXCR4 ligand, CXCL12, within the corpus callosum (CC) during cuprizone (CPZ) intoxication and …

The neuropathology of chronic relapsing experimental allergic encephalomyelitis induced in the Lewis rat by inoculation with whole spinal cord and treatment with cyclosporin A.

Chronic relapsing experimental allergic encephalomyelitis was induced in Lewis rats by inoculation with guinea-pig spinal cord and complete … horacic spinal cord, and lesions of different ages were present within the spinal cord, CNS and PNS remyelination by oligodendrocytes and Schwann cells, respectively, was present in all animals studied later than 18 days after inoculation (the time of the first remission, if it occurred). In both early and late clinically active disease electron microscopy reve …

Unlocking dexmedetomidine's therapeutic potential in multiple sclerosis: Dual modulation of PI3K/Akt/BDNF and TLR4/NF-κB pathways in EAE rats.

Multiple sclerosis (MS) is an enduring autoimmune and neurodegenerative disease affecting the central nervous system with inflammation, demyelination, and axonal degeneration that progresses to neurological impairment. Despite available treatments, their limited efficacy, inability to promote remyelination, and associated adverse reactions highlight the need for unconventional therapies. This study investigated the therapeutic potential of dexmedetomidine (DEX), a selective α2-adrenergic receptor (α2AR) agonist, in a rat model of MS triggered by experimental autoimmune encephalomyelitis (EAE).…

Investigating the use of cuprizone and lysolecithin to model demyelination ex vivo in sagittal rat brain organotypic slice cultures.

INTRODUCTION: The development of organotypic slice cultures of central nervous system (CNS) tissues has bridged the gap between simple in vitro cell cultures and complex in vivo whole animal studies. Organotypic brain slice cultures are a useful tool to study neurological disease, providing a more complex 3-dimensional system than standard 2-dimensional in vitro cell culture. In particular, organotypic brain slice cultures provide an excellent model to study the processes of demyelination and remyelination associated with neurological disease and injury. However, organotypic brain slice cultur…

Нейропзащитное воздействие грелина на крысиную модель множественных склерозов.

Множественный склероз (MS) является воспалительным заболеванием центральной нервной системы, характеризующимся обезвоживанием и аксонной потерей, и является основной причиной нетравматических неврологических расстройств у молодых людей. Несмотря на то, что существует несколько методов лечения этого заболевания, не существует окончательного средства для лечения множественных склерозов. Известно, что воспаление и окислительный стресс играют важную роль в патофизиологии MS. Грелин, пептид, скрытый желудком, обладает нейрозащитными свойствами по нескольким путям, включая ослабление окислительного

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is an inflammatory central nervous system disease characterized by demyelination and axonal loss and is the main cau … randomly divided into six groups: Control groups (Control35 and Control-S42), demyelination group, remyelination group, remyelination + ghrelin (20 µg/kg) group and remyelination + ghrelin (40 µg/kg) group. Y maze test was performed on the rats on their last day of the experiment. Oxidative stress and inflammatory parameters were investigated in brain using co …

Quercetin treatment regulates the Na+,K+-ATPase activity, peripheral cholinergic enzymes, and oxidative stress in a rat model of demyelination.

Quercetin is reported to exert a plethora of health benefits through many different mechanisms of action. This versatility and presence in t … with vehicle (ethanol 20%) or quercetin 50 mg/kg for 7 (demyelination phase, by gavage) or 21 days (remyelination phase) after EB (0.1%, 10 μL) injection (intrapontine).The encephalon was removed, and the pons, hypothalamus, cerebral cortex, hippocampus, striatum, and cerebellum were dissected to verify the Na+,K+-ATPase activity. Our results showed that querce …

Cystatin F attenuates neuroinflammation and demyelination following murine coronavirus infection of the central nervous system.

BACKGROUND: Cystatin F is a secreted lysosomal cysteine protease inhibitor that has been implicated in affecting the severity of demyelination and enhancing remyelination in pre-clinical models of immune-mediated demyelination. How cystatin F impacts neurologic disease severity following viral infection of the central nervous system (CNS) has not been well characterized and was the focus of this study. We used cystatin F null-mutant mice (Cst7-/-) with a well-established model of murine coronavirus-induced neurologic disease to evaluate the contributions of cystatin F in host defense, demyelin…

Энергометаболический баланс олигодендроцитов в многоразовом склерозе: механизмы, сетевое сцепление и достижения в метаболических-трапезах.

Олигодендроциты (ОИ) — клетки центральной нервной системы (КНС), образующие миелин, — являются основными объектами аутоиммунной атаки при множественном склерозе (МС), что приводит к демиелинации и поврежденному нейронному введению. Недавние исследования свидетельствуют о том, что у пациентов с MS белые вещества увеличивают аэробный гликолиз наряду с сокращением потребления кислорода - метаболическое несоответствие между использованием глюкозы и потреблением кислорода, которое коррелирует с накоплением инвалида. Дисрегламентированный метаболизм энергии также является центральным механизмом, огр

Совпадение в аннотации оригинала
Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system (CNS), are principal targets of autoimmune attack in multiple … s with disability accumulation. Dysregulated energy metabolism is also a central mechanism limiting remyelination in MS. In MS, this dysregulation is characterized primarily by abnormal availability of metabolic substrates entering the CNS; in turn, it disrupts glucose and lipid metabolism within OLs, leading to mitochondrial dysfunction and a diminished capaci …

A long-term observation of olfactory ensheathing cells transplantation to repair white matter and functional recovery in a focal ischemia model in rat.

Trials of neuroprotection in ischemic stroke mainly concern gray matter protection, with little information on white matter damage. Olfactory ensheathing cells (OECs) are capable of providing continuous neurotrophic factor and of promoting growth and remyelination of damaged axons. We evaluated OECs for the repair of white matter after transplantation in middle cerebral artery occlusion (MCAO) rat. OECs were cultured from the olfactory bulbs of adult green fluorescent protein (GFP)-expressing transgenic rats and transplanted into peri-infarct basal ganglia imminently after reperfusion. The mor…

Targeting the Subventricular Zone to Promote Myelin Repair in the Aging Brain.

The subventricular zone (SVZ) is the largest and most active germinal zone in the adult forebrain. Neural stem cells (NSCs) of the SVZ generate olfactory interneurons throughout life and retain the intrinsic ability to generate oligodendrocytes (OLs), the myelinating cells of the central nervous system. OLs and myelin are targets in demyelinating diseases such as multiple sclerosis (MS). Remyelination is dependent on the ability of oligodendrocyte progenitor cells (OPCs) to proliferate, migrate, and terminally differentiate into myelinating OLs. During aging, there is a gradual decrease in the…

Astrocyte-specific FoxF2 modulates immune and myelin repair: Evidence from multiple sclerosis lesions and an animal model.

As multiple sclerosis (MS) progresses, myelin repair becomes inefficient. To gain insight into the underlying causes, we RNA-sequenced postm … repair. To investigate how FoxF2 may influence repair, we examined cuprizone (CPZ)-induced de- and remyelination in CreERT2 FoxF2flox/flox conditional knockout (FoxF2 KO) mice. In the absence of FoxF2, RNA sequencing of the isolated corpus callosum (CC) showed high gene activation during demyelination and reduced gene activation during remyelination. Upregulat …

Schwann Cell Synthesized Cholesterol Orchestrates Peripheral Nerve Regeneration via Structural and IGF1-Dependent Signaling Mechanisms.

Peripheral nerve myelin is the most cholesterol-rich structure in the body, with the majority of cholesterol being synthesized by Schwann Ce … e crush injury. Mechanistically, SCs' Fdft1 deficiency not only disrupts the cholesterol supply for remyelination but also suppresses the secretion of insulin-like growth factor 1 (IGF1). This impairment of IGF1 signaling further attenuates the axonal regeneration by paracrine mechanisms and disrupts the remyelination via a novel IGF1R/Rap1/PI3K/AKT axis within …

Множественный склероз: то, что мы узнали и можем узнать из электронной микроскопии.

Множественный склероз (MS) — воспалительное нейродегенеративное заболевание, характеризующееся возникновением демиелинированных повреждений в центральной нервной системе. Повреждения MS могут подвергаться воспоминанию, временно смягчая симптомы, но по мере развития болезни воспроизводство становится менее эффективным. Помимо повреждений, нормальные появляющиеся ткани мозга имеют тонкие изменения, потенциально указывающие на более широкую диффузную патологию и/или повышенную подверженность воздействию повреждений. Патология MS варьируется между повреждениями серых и белых веществ и их нормальны

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is an inflammatory neurodegenerative disease marked by the formation of demyelinated lesions in the central nervous system. MS lesions can undergo remyelination, temporarily alleviating symptoms, but as the disease advances, remyelination becomes less effective. Beyond lesions, normal-appearing brain tissue exhibits subtle alterations…

Эстрадиол содействует ремонту Myelin в Spinal Cord of Women Mice в CXCR4 Chemokine Receptor-Nependent.

В центральной нервной системе для взрослых (ЦНС) регенерация миелина происходит главным образом за счет дифференциации клеток олигодендроцитов потомства на зрелые олигодендроциты. У мужчин снижение уровня тестостерона ускоряет развитие множественных склерозов (МС), в то время как у женщин менопауза усугубляет инвалидность, связанную с НР. Ранее мы продемонстрировали, что функциональные яички и тестостерон необходимы для спонтанной ремимиилации фокус-лизолицитина (LPC), вызванной демиелином повреждения позвоночника мужских мышей. Ремонт миелина на основе тестостерона зависел от введения хемокин

Совпадение в аннотации оригинала
In the adult central nervous system (CNS), myelin regeneration primarily occurs through the differentiation of oligodendrocyte progenitor ce … We previously demonstrated that functional testes and testosterone are required for the spontaneous remyelination of a focal lysolecithin (LPC)-induced demyelinating lesion in the spinal cords of male mice. Testosterone-dependent myelin repair was dependent on the induction of the chemokine receptor CXCR4 in astrocytes that repopulated the lesion and on coopera …

Acid-sensing ion channel-1 contributes to the failure of myelin sheath regeneration following spinal cord injury by transcellular delivery of PGE2.

BACKGROUND: Traumatic injuries to spinal cord lead to severe motor, sensory, and autonomic dysfunction. The accumulation of inhibitory compounds plays a pivotal role in the secondary damage to sparing neural tissue and the failure of axonal regeneration and remyelination. Acid-sensing ion channel-1(ASIC1A) is widely activated following neurotrauma, including spinal cord injury (SCI). However, its role in SCI remains elusive. METHODS: The effects of acidic environment on the differentiation and genes changes of neural stem cells (NSCs) were assessed by immunofluorescence staining and RNA-seque…

Optic Neuritis in Multiple Sclerosis-A Review of Molecular Mechanisms Involved in the Degenerative Process.

Multiple sclerosis is a central nervous system inflammatory demyelinating disease with a wide range of clinical symptoms, ocular involvement being frequently marked by the presence of optic neuritis (ON). The emergence and progression of ON in multiple sclerosis is based on various pathophysiological mechanisms, disease progression being secondary to inflammation, demyelination, or axonal degeneration. Early identification of changes associated with axonal degeneration or further investigation of the molecular processes underlying remyelination are current concerns of researchers in the field …