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Последние достижения в области мезенхимической стволовой клеточной терапии для множественных склерозов: клинические виды применения и проблемы.

Множественный склероз (MS), хроническое аутоиммунное расстройство центральной нервной системы (CNS), характеризуется воспалением, обезвоживанием и нейродегенерацией, что приводит к различным клиническим проявлениям, таким, как усталость, сенсорное расстройство и когнитивная дисфункция. Текущее фармакологическое лечение направлено прежде всего на иммунную модуляцию, но не позволяет остановить прогрессию заболеваний или полностью обратить на нет повреждения CNS. Лечение стволовыми клетками (MSC) является многообещающей альтернативой, используя иммуномудуляторы, нейрозащиту и регенеративные спосо

Совпадение в аннотации оригинала
Multiple sclerosis (MS), a chronic autoimmune disorder of the central nervous system (CNS), is characterized by inflammation, demyelination, … an in-depth analysis of MSC mechanisms of action, including immune system regulation, promotion of remyelination, and neuroregeneration. It examines preclinical studies and clinical trials evaluating the efficacy, safety, and limitations of MSC therapy in various MS phenotypes. Special attention is given to challenges such as delivery routes, dosing regimens, …

Нейроинфламмация: Олигодендроцентрический вид.

Хроническая нейроинфламмация, движущаяся астроцитами и микроглией центральной нервной системы (ЦНС), а также инфильтрация периферической иммунной системы являются важным патологическим механизмом по целому ряду неврологических заболеваний. В течение десятилетий исследования были сосредоточены почти исключительно на том, как нейроинфламмация повлияла на нейронную функцию; однако накоплены доказательства того, что повреждение олигодендроцита является важным компонентом как патологического, так и клинического исхода. Хотя олигодендроциты могут пройти процесс внутреннего ремонта, известный как рем

Совпадение в аннотации оригинала
Chronic neuroinflammation, driven by central nervous system (CNS)-resident astrocytes and microglia, as well as infiltration of the peripher … clinical outcomes. While oligodendrocytes are able to undergo an endogenous repair process known as remyelination, this process becomes inefficient and usually fails in the presence of sustained inflammation. The present review focuses on our current knowledge regarding activation of the innate and adaptive immune systems in the chronic demyelinating disease, m …

Изоляция олигодендроцитных ячеек прекурсора с иммуномагнитными бортами для их лучшей жизнеспособности в Витро и Ин Виво.

Олигодендроциты (Olgodendrocytes) являются глиальными клетками, которые миленизируют аксоны в центральной нервной системе (CNS). Эти клетки образуются из олигодендроцитов-прекурсоров (ОРК) в ходе развития CNS, и население ОКН, остающееся у взрослого, несет ответственность за спонтанное ремиилирование таких демиелионирующих заболеваний, как множественный склероз (MS). Таким образом, ОПС представляют собой интересный источник регенеративной терапии. Здесь мы описываем обновленный протокол изоляции ОПС, основанный на технологии отделения магнитных клеток (MACS) и олигодендроглиальных маркеров. По

Совпадение в аннотации оригинала
Oligodendrocytes (OLs) are glial cells that myelinate axons in the central nervous system (CNS). These cells are generated from oligodendrocyte precursor cells (OPCs) during CNS development, and the population of OPCs that remain in the adult is responsible for spontaneous remyelination in demyelinating diseases such as multiple sclerosis (MS). Thus, OPCs re…

[SEVERE INFECTIOUS DISEASE AS A PREDICTOR OF CRITICAL ILLNESS ENCEPHALOPATHY IN CHILDREN (CLINICAL CASE)].

In childhood, infectious diseases, as a rule, are generalized in nature with the development of urgent or critical conditions that require the transfer of the child to mechanical ventilation. A child's stay on mechanical ventilation, on the one hand, is vital, on the other hand, it is a factor that threatens the development of acute encephalopathy, mechanical ventilation associated pneumonia, polyneuropathy and myopathy of critical conditions. According to the authors, the incidence of critical encephalopathy in patients with generalized infectious diseases who are on mechanical ventilation is

Behavioural phenotypes in the cuprizone model of central nervous system demyelination.

The feeding of cuprizone (CPZ) to animals has been extensively used to model the processes of demyelination and remyelination, with many papers adopting a narrative linked to demyelinating conditions like multiple sclerosis (MS), the aetiology of which is unknown. However, no current animal model faithfully replicates the myriad of symptoms seen in the clinical condition of MS. CPZ ingestion causes mitochondrial and endoplasmic reticulum stress and subsequent apoptosis of oligodendrocytes leads to central nervous system demyelination and glial cell activation. Although there are a wide variety…

RalGTPases contribute to Schwann cell repair after nerve injury via regulation of process formation.

RalA and RalB are small GTPases that are involved in cell migration and membrane dynamics. We used transgenic mice in which one or both GTPases were genetically ablated to investigate the role of RalGTPases in the Schwann cell (SC) response to nerve injury and repair. RalGTPases were dispensable for SC function in the naive uninjured state. Ablation of both RalA and RalB (but not individually) in SCs resulted in impaired axon remyelination and target reinnervation following nerve injury, which resulted in slowed recovery of motor function. Ral GTPases were localized to the leading lamellipodia…

Multiple sclerosis, and other demyelinating and autoimmune inflammatory diseases of the central nervous system.

Multiple sclerosis (MS) is characterized by a substantial degree of heterogeneity in relation to clinical manifestations, disease course, ra … activation/inflammatory biomarkers; oxidative stress biomarkers; neuroaxonal damage biomarkers; and remyelination and demyelination biomarkers.

[A clinical-electroneuromyographic study of the efficacy of ipidacrine in patients with mononeuropathies].

OBJECTIVE: To evaluate the efficacy and tolerability of axamon (ipidacrine) therapy in patients with focal neuropathies--mononeuropathies. … e hand and feet; increased nerve conduction velocity in the peripheral nerves as a manifestation of remyelination activity, and others). CONCLUSION: The obtained clinical and ENMG data indicate that axamon (ipidacrine) is a unique cholinesterase inhibitor with conduction action primarily targeting on efferent (motor) fibers of the peripheral nerves.

Nimodipine promotes regeneration and functional recovery after intracranial facial nerve crush.

The calcium flow inhibitor, nimodipine, has been shown to promote motor neuron survival in the facial nucleus after intracranial facial nerv … the possibility of using this substance for new clinical applications to promote axonal growth and remyelination.

Peripheral nerve lesions in HTLV-I associated myelopathy (HAM/TSP).

Peripheral nerve dysfunction (PND) was found in as many as 43% of our patients with human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM/TSP). To evaluate the PND further we biopsied the sural nerve in 6 patients. The histological features were varying degrees of demyelination, remyelination, axonal atrophy and degeneration, and perineurial fibrosis. "Globule" or "sausage" formation was prominent in two of the specimens. Inflammatory infiltrates were absent. No deposits of IgG, IgM, IgA, or complement were detected in the biopsies. No viral antigen or proviral DNA was det…

Experimental germanium dioxide-induced neuropathy in rats.

We report an experimental model of germanium dioxide (GeO2)-induced neuropathy in rats. More than 6 months administration of GeO2 to young rats produced neuropathy characterized by segmental demyelination/remyelination and nerve edema. Electron microscopic studies demonstrated that changes in Schwann cells, such as an increased cytoplasmic volume or disintegration of the cytoplasm, were the earliest pathological findings. Schwann cell mitochondria contained high electron-dense materials. Subsequent removal of necrotic Schwann cell debris and myelin by invading macrophages was evident. These fi…

Thin axons relative to myelin spiral length in hereditary motor and sensory neuropathy, type I.

The relationship of axonal to myelin area in semithin transverse sections of myelinated fibers obtained from sural nerves at the ankle level … in distal aspects of lumbosacral neurons and associated with secondary segmental demyelination and remyelination and hypertrophic neuropathy, preceding distal axonal loss. Because the process may begin in utero or in infancy, not only atrophy but also maldevelopment of axons may be involved.

Electron microscopic observations on allergic encephalomyelitis in the rabbit.

Allergic encephalomyelitis was produced in rabbits by injection of white matter from bovine brain plus adjuvants. Electron microscopy revealed focal demyelinization in both the spinal roots and cord. The peripheral lesions were characterized by vacuolization of Schwann cytoplasm, destruction of the myelin sheath, and by some appearances suggesting remyelinization. In the cord there was a marked perivascular inflammatory infiltration with focal destruction of the blood-brain barrier as demonstrated by formation of an abnormal interstitial space about capillaries. Mitochondria of oligodendroglia

Neuroprotective effects of rutin against cuprizone-induced multiple sclerosis in mice.

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system that injures the myelin sheath, pr … gnificantly improved locomotor activity and motor coordination. Moreover, RUT considerably improved remyelination in the CC of CPZ + RUT-treated mice, as revealed by luxol fast blue staining and transmission electron microscopy. Rutin also significantly attenuated CPZ-induced oxidative stress and inflammation in the CC of tested animals. The effect of RUT100 wa …

Identifying Lanthionine Ketimine Derivatives for Maturation and Proliferative Effects in Oligodendrocyte Progenitor Cells.

Previous studies have shown that lanthionine ketimine ethyl ester (LKE) reduces clinical scores in the experimental autoimmune encephalomyelitis (EAE) mouse model of Multiple Sclerosis, induces differentiation of oligodendrocyte progenitor cells (OPCs) in vitro, and accelerates remyelination following cuprizone induced demyelination. In a search for derivatives with greater efficacy to induce OPC maturation or proliferation, we screened a panel of 2-alkyl and 3-phosphonate substituted LK derivatives. Incubation of Oli-neu oligodendrocyte cells with 2-n-butyl- or 2-n-hexyl-LKE-phosphonate reduc…

Обобщение и оценка 6-ариламинобензамидов в качестве позитронных фотографических лигандов для рецептора фингозина-1-фосфата-5.

Спингосин-1-фосфат-5 (S1P5) является одним из пяти мембранных белковых рецепторов G, которые активируются лизофосфолипидом, фосфатом-1, что приводит к регулированию многих клеточных процессов. Рецепторы S1P5 расположены на олигодендроцитах и предлагаются для оказания влияния на физиологию олигодендроцитов. Понимание модуляции S1P5 в ходе таких процессов, как ремиелионация, может иметь потенциальные возможности для демиелионизации расстройств CNS, таких, как множественный склероз (MS). В этой связи мы сообщаем об обобщении и предварительной оценке серии фторированных 6-ариламинобензамидов в кач

Совпадение в аннотации оригинала
The sphingosine-1-phosphate-5 (S1P5) receptor is one of the five membrane G protein-coupled receptors that are activated by the lysophosphol … sed to influence oligodendrocyte physiology. Understanding S1P5 modulation during processes such as remyelination could have potential applications for demyelinating CNS disorders such as multiple sclerosis (MS). Herein, we report the synthesis and preliminary evaluation of a series of fluorinated 6-arylaminobenzamides as positron emission tomography (PET) liga …

Meningeal lymphatic function promotes oligodendrocyte survival and brain myelination.

The precise neurophysiological changes prompted by meningeal lymphatic dysfunction remain unclear. Here, we showed that inducing meningeal lymphatic vessel ablation in adult mice led to gene expression changes in glial cells, followed by reductions in mature oligodendrocyte numbers and specific lipid species in the brain. These phenomena were accompanied by altered meningeal adaptive immunity and brain myeloid cell activation. During brain remyelination, meningeal lymphatic dysfunction provoked a state of immunosuppression that contributed to delayed spontaneous oligodendrocyte replenishment a…

BTK inhibition limits microglia-perpetuated CNS inflammation and promotes myelin repair.

In multiple sclerosis (MS), persisting disability can occur independent of relapse activity or development of new central nervous system (CN … ated BTK inhibition promoted the clearance of myelin debris by microglia, leading to an accelerated remyelination. These findings highlight that BTK inhibition has the potential to counteract underlying chronic progression of MS.

BMAL1 loss in oligodendroglia contributes to abnormal myelination and sleep.

Myelination depends on the maintenance of oligodendrocytes that arise from oligodendrocyte precursor cells (OPCs). We show that OPC-specific … tation. OPC-specific Bmal1 loss in adulthood does not alter OPC density at baseline but impairs the remyelination of a demyelinated lesion driven by changes in OPC morphology and migration. Lastly, we show that sleep fragmentation is associated with increased prevalence of the demyelinating disorder multiple sclerosis (MS), suggesting a link between MS and slee …

Neural mobilization promotes nerve regeneration by nerve growth factor and myelin protein zero increased after sciatic nerve injury.

Neurotrophins are crucial in relation to axonal regrowth and remyelination following injury; and neural mobilization (NM) is a noninvasive therapy that clinically is effective in neuropathic pain treatment, but its mechanisms remains unclear. We examined the effects of NM on the regeneration of sciatic nerve after chronic constriction injury (CCI) in rats. The CCI was performed on adult male rats, submitted to 10 sessions of NM, starting 14 days after CCI. Then, the nerves were analyzed using transmission electron microscopy and western blot for neural growth factor (NGF) and myelin protein ze…