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The Long-Term Efficacy Study of Multiple Allogeneic Canine Adipose Tissue-Derived Mesenchymal Stem Cells Transplantations Combined With Surgery in Four Dogs With Lumbosacral Spinal Cord Injury.

Severe lumbosacral pain, paraparesis or paraplegia, and urinary incontinence are common but frustrating problems in dogs with lumbosacral spinal cord injury (SCI). The surgical interventions including stabilization and decompression may not restore satisfying neurological functions in severe SCI. Adipose tissue-derived mesenchymal stem cells (Ad-MSCs) show benefits in immunomodulation, anti-inflammation, and promotion of axonal growth and remyelination, and also display efficacy in several diseases in veterinary medicine. In this report, four dogs presented with fracture of sacrum vertebrae or…

Exosomes derived from astrocytes after oxygen-glucose deprivation promote differentiation and migration of oligodendrocyte precursor cells in vitro.

BACKGROUND: Excessive release of glutamate, oxidative stress, inflammation after ischemic brain injury can lead to demyelination. Astrocytes participate in the maturation and differentiation of oligodendrocyte precursor cells (OPCs), and play multiple roles in the process of demyelination and remyelination. Here, we studied the role of Astrocyte-derived exosomes (AS-Exo) under ischemic conditions in proliferation, differentiation and migration of OPCs in vitro. METHODS AND RESULTS: Exosomes were collected from astrocytes supernatant by differential centrifugation from control astrocytes (CTex…

Exercise rapidly alters proteomes in mice following spinal cord demyelination.

Exercise affords broad benefits for people with multiple sclerosis (PwMS) including less fatigue, depression, and improved cognition. In animal models of multiple sclerosis (MS), exercise has been shown to improve remyelination, decrease blood-brain barrier permeability and reduce leukocyte infiltration. Despite these benefits many PwMS refrain from engaging in physical activity. This barrier to participation in exercise may be overcome by uncovering and describing the mechanisms by which exercise promotes beneficial changes in the central nervous system (CNS). Here, we show that acute bouts o…

Neurodynamics: is tension contentious?

Tensioning techniqueswere the first neurodynamic techniques used therapeutically in the management of people with neuropathies. This article … opioid receptors, reduced fibrosis and intraneural scar formation, improved nerve regeneration and remyelination, increased muscle power and locomotion, less mechanical and thermal hyperalgesia and allodynia, and improved conditioned pain modulation. However, animal and cellular models also show that 'excessive' tensile forces have negative effects on the nerv …

N-myc downstream regulated family member 1 (NDRG1) is enriched in myelinating oligodendrocytes and impacts myelin degradation in response to demyelination.

The N-myc downstream regulated gene family member 1 (NDRG1) is a gene whose mutation results in peripheral neuropathy with central manifesta … porter mouse (TgNdrg1-EGFP). We report NDRG1 expression during developmental myelination and during remyelination after cuprizone-induced demyelination of the adult corpus callosum. The transcriptome of Ndrg1-EGFP+ cells further supports the identification of late myelinating oligodendrocytes, characterized by expression of genes regulating lipid metabolism and …

Epigenetic insights into multiple sclerosis disease progression.

Multiple sclerosis (MS), a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system, is today a leadin … of DNA and histone modifications in impaired oligodendrocyte differentiation, defective myelination/remyelination and sustained neuro-axonal vulnerability. We next explore possibilities for identifying factors affecting progression using easily accessible tissues such as blood by comparing epigenetic signatures in peripheral immune cells and brain tissue. Despi …

Methods of olfactory ensheathing cell harvesting from the olfactory mucosa in dogs.

Olfactory ensheathing cells are thought to support regeneration and remyelination of damaged axons when transplanted into spinal cord injuries. Following transplantation, improved locomotion has been detected in many laboratory models and in dogs with naturally-occurring spinal cord injury; safety trials in humans have also been completed. For widespread clinical implementation, it will be necessary to derive large numbers of these cells from an accessible and, preferably, autologous, source making olfactory mucosa a good candidate. Here, we compared the yield of olfactory ensheathing cells fr…

Differentiation of Human Tonsil-Derived Mesenchymal Stem Cells into Schwann-Like Cells Improves Neuromuscular Function in a Mouse Model of Charcot-Marie-Tooth Disease Type 1A.

Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited motor and sensory neuropathy, and is caused by duplication of PMP22 … erve and muscle in Tr-J mice. Histological and molecular analyses showed the possibility of in situ remyelination by T-MSC-SCs transplantation. These findings demonstrate that the transplantation of heterologous T-MSC-SCs induced neuromuscular regeneration in mice and suggest they could be useful for the therapeutic treatment of patients with CMT1A disease.

Upregulation of Myelin Gene Expression by a Physically-Modified Saline via Phosphatidylinositol 3-Kinase-Mediated Activation of CREB: Implications for Multiple Sclerosis.

An increase in central nervous system (CNS) remyelination and a decrease in CNS inflammation are important steps to halt the progression of multiple sclerosis (MS). RNS60 is a bioactive aqueous solution generated by subjecting normal saline to Taylor-Couette-Poiseuille flow under elevated oxygen pressure. Recently we have demonstrated that RNS60 exhibits anti-inflammatory properties. Here, we describe promyelinating property of RNS60. RNS60, but not normal saline (NS), RNS10.3 (TCP-modified saline without excess oxygen) or PNS60 (saline containing excess oxygen without TCP modification), stimu…

Autoimmune nodo-paranodopathies of peripheral nerve: the concept is gaining ground.

Peripheral neuropathies are classified as primarily demyelinating or axonal. Microstructural alterations of the nodal region are the key to … odo-paranodopathy category because nerve injury is due to dismantling of the paranode, segmental de-remyelination is absent and the pathogenic mechanism is not inflammatory. Evidence from nerve conductions and electron microscopy studies in patients and mutant animal models can reconcile the apparent contrast between the electrophysiological 'demyelinating' fea …

Effects of abstinence and chronic cigarette smoking on white matter microstructure in alcohol dependence: Diffusion tensor imaging at 4T.

BACKGROUND: We previously reported widespread microstructural deficits of brain white matter in alcohol-dependent individuals (ALC) compared … ain abstinence, via smoking cessation, cognitive-based therapy, and perhaps pharmacology to support remyelination.

Cooperative interaction of hepatocyte growth factor and neuregulin regulates Schwann cell migration and proliferation through Grb2-associated binder-2 in peripheral nerve repair.

The sequential reactive changes in Schwann cell phenotypes in transected peripheral nerves, including dedifferentiation, proliferation and m … erve injury was principally regulated by the neuregulin 1-ErbB2 signaling and was indispensable for remyelination after crush injury, but not for the proliferation and migration of Schwann cells. Our findings indicate that Gab1 and Gab2 in Schwann cells are nonredundant and play a crucial role in peripheral nerve repair.

Gabapentin attenuates neuropathic pain and improves nerve myelination after chronic sciatic constriction in rats.

Gabapentin (GBP) is an anti-convulsive drug often used as analgesic to control neuropathic pain. This study aimed at evaluating oral GBP tre … -related behaviors and improved later nerve morphology. Our findings suggest that GBP improve nerve remyelination after chronic constriction of the sciatic nerve.

Longitudinally extensive NMO spinal cord pathology produced by passive transfer of NMO-IgG in mice lacking complement inhibitor CD59.

Spinal cord pathology with inflammatory, demyelinating lesions spanning three or more vertebral segments is a characteristic feature of neur … ion, and demyelination. Hind limb motor function was remarkably impaired as well. There was partial remyelination and recovery of motor function by day 5. Our results implicate CD59 as an important modulator of the immune response in NMO, and provide a novel animal model of NMO that closely recapitulates human NMO pathology. Up-regulation of CD59 on astrocytes …

Central effects of fingolimod.

INTRODUCTION: Fingolimod, a sphingosine-1-phosphate receptor modulator, was the first oral therapy approved for relapsing-remitting multiple … godendrocytes, oligodendrocyte precursor cells, astrocytes, microglial cells and neurons, promoting remyelination, neuroprotection, and endogenous regeneration processes. Efficacy results from clinical trials are consistent with a mechanism of action that includes direct effects in CNS cells. CONCLUSIONS: Current evidence suggests that the efficacy of fingolim …

A novel cell transplantation protocol and its application to an ALS mouse model.

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease, which selectively affects motor neurons throughout the central nervous system. The extensive distribution of motor neurons is an obstacle to applying cell transplantation therapy for the treatment of ALS. To overcome this problem, we developed a cell transplantation method via the fourth cerebral ventricle in mice. We used mouse olfactory ensheathing cells (OECs) and rat mesenchymal stem cells (MSCs) as donor cells. OECs are reported to promote regeneration and remyelination in the spinal cord, while MSCs have a capabil…

Peripheral nervous system and central nervous system pathology in rapidly progressive lower motor neuron syndrome with immunoglobulin M anti-GM1 ganglioside antibody.

Pathological studies, including novel teased peripheral nerve fiber studies, were performed in a patient who presented with a rapidly progre … s. Sectional studies of single myelinated nerve fibers from an antemortem sural nerve biopsy showed remyelination and globular paranodal swellings due to focal complex myelin folding and degeneration in 13% of fibers. Postmortem studies of the sural nerves 4 weeks later showed paranodal demyelination (90% of fibers), but no paranodal swellings and similar findi …

Роль рецептора печени Х в множестве склероза: долгая жизнь за барьером.

Рецепторы печени X (LXRs) являются ядерными рецепторами, которые функционируют в качестве транскрипционных факторов, регулирующих метаболизм холестерина, и связаны с множественным склерозом (MS) патогенезом. Цель этого мини-обзора состоит в том, чтобы прояснить потенциальную роль ЛХР в нейропатологии MS. MS является наиболее распространенным воспалительным и демиелинизирующим заболеванием центральной нервной системы (CNS), воздействующим как на мозг, так и на спинной мозг. Кроме того, изменения в метаболизме холестерина мозга в MS могут изменить функциональную активность и иммунную реакцию LXR

Совпадение в аннотации оригинала
Liver X receptors (LXRs) are nuclear receptors that function as transcription factors regulating cholesterol metabolism and are implicated i … d anti-inflammatory properties involved in immune regulation and clearance of debris as well as the remyelination process. LXRs regulate the functional activity of glial cells and prevent glial cell-mediated neurodegeneration. LXRs have an important role in the regulation of neuroinflammation during MS neuropathology. LXRs may prevent the progression of neuroin …

Pharmacological modulation of inflammatory oligodendrocyte progenitor cells using three multiple sclerosis disease modifying therapies in vitro.

Preclinical studies of pro-remyelinating therapies for multiple sclerosis tend to neglect the effect of the disease-relevant inflammatory milieu. Interferon-gamma (IFN-γ) is known to suppress oligodendrocyte progenitor cell (OPC) differentiation and induce a recently described immune OPC (iOPC) phenotype characterized by expression of major histocompatibility complex (MHC) molecules. We tested the effects of cladribine (CDB), dimethylfumarate (DMF), and interferon-beta (IFN-β), existing anti-inflammatory therapies for MS, on the IFN-γ-induced iOPC formation and OPC differentiation block. In li

Regeneration of Propriospinal Axons in Rat Transected Spinal Cord Injury through a Growth-Promoting Pathway Constructed by Schwann Cells Overexpressing GDNF.

Unsuccessful axonal regeneration in transected spinal cord injury (SCI) is mainly attributed to shortage of growth factors, inhibitory glial scar, and low intrinsic regenerating capacity of severely injured neurons. Previously, we constructed an axonal growth permissive pathway in a thoracic hemisected injury by transplantation of Schwann cells overexpressing glial-cell-derived neurotrophic factor (SCs-GDNF) into the lesion gap as well as the caudal cord and proved that this novel permissive bridge promoted the regeneration of descending propriospinal tract (dPST) axons across and beyond the l