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1.
Brain Behav Immun ; 77: 110-126, 2019 03.
Article in English | MEDLINE | ID: mdl-30582962

ABSTRACT

Remyelination is an endogenous process by which functional recovery of damaged neurons is achieved by reinstating the myelin sheath around axons. Remyelination has been documented in multiple sclerosis (MS) lesions and experimental models, although it is often incomplete or fails to affect the integrity of the axon, thereby leading to progressive disability. Microglia play a crucial role in the clearance of the myelin debris produced by demyelination and in inflammation-dependent OPC activation, two processes necessary for remyelination to occur. We show here that following corpus callosum demyelination in the TMEV-IDD viral murine model of MS, there is spontaneous and partial remyelination that involves a temporal discordance between OPC mobilization and microglia activation. Pharmacological treatment with the endocannabinoid 2-AG enhances the clearance of myelin debris by microglia and OPC differentiation, resulting in complete remyelination and a thickening of the myelin sheath. These results highlight the importance of targeting microglia during the repair processes in order to enhance remyelination.


Subject(s)
Arachidonic Acids/pharmacology , Endocannabinoids/pharmacology , Glycerides/pharmacology , Microglia/drug effects , Remyelination/drug effects , Animals , Arachidonic Acids/metabolism , Axons/metabolism , Cell Differentiation/physiology , Corpus Callosum/pathology , Corpus Callosum/physiology , Demyelinating Diseases/physiopathology , Disease Models, Animal , Endocannabinoids/metabolism , Female , Glycerides/metabolism , Male , Mice , Mice, Inbred Strains , Microglia/metabolism , Multiple Sclerosis/metabolism , Multiple Sclerosis/physiopathology , Myelin Sheath/metabolism , Oligodendrocyte Precursor Cells/physiology , Oligodendroglia/metabolism , Theilovirus/pathogenicity
2.
Trauma (Majadahonda) ; 25(4): 219-225, oct.-dic. 2014. tab, ilus
Article in Spanish | IBECS | ID: ibc-132823

ABSTRACT

Objetivo: Estudiar la actividad de la neurostatina obtenida enzimáticamente y purificada mediante un nuevo método, en cultivos de células implicadas en la formación de la cicatriz glial. Material y métodos: La neurostatina se obtuvo mediante una reacción enzimática a partir del gangliósido GD1b comercial y se purificó con un método nuevo simplificado. La actividad de la neurostatina se probó en ensayos de proliferación con MTT en pericitos y microglía de rata. Resultados: La actividad de la neurostatina purificada fue similar a la obtenida mediante purificación a partir de cerebro de mamífero. La neurostatina inhibió la proliferación de los pericitos inducida por el factor de crecimiento PDGF-B y la proliferación de la microglía de rata inducida por la toxina bacteriana LPS a concentraciones nanomolar. Conclusión: La nueva metodología de obtención y purificación de la neurostatina y su actividad justifican su ensayo en modelos de lesión del SNC en animales, para evaluar su posible uso como terapia en pacientes con lesiones del SNC (AU)


Objective: To study the activity of neurostatin obtained enzymatically and purified using a new method, in cultures of cells involved in the formation of the glial scar. Material and methods: Neurostatin was obtained from the commercial ganglioside GD1b, using enzymatic Oacetylation, and was purified by a new simplified method. The activity of neurostatin was tested by an MTT proliferation assay in pericytes and rat microglial cells. Results: The activity of neurostatin obtained and purified by this new method was similar to the neurostatin obtained by the purification from mammalian brain. Neurostatin inhibited the PDGF-B growth factor induced proliferation of pericytes and LPS bacteria toxin induced proliferation of rat microglial cells at nanomolar concentrations. Conclusion: This new methodology to synthesize and purify neurostatin and its activity justify further studies to test its effect in animal models of CNS injuries and to evaluate its possible use as a therapy in patients with CNS injuries (AU)


Subject(s)
Animals , Male , Female , Rats , Central Nervous System , Central Nervous System/injuries , Microglia , Microglia/enzymology , Pericytes , Pericytes/enzymology , Muscles , Muscles/enzymology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/analysis , Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemical synthesis , Central Nervous System/enzymology , Models, Animal , Inflammation/enzymology , Inflammation/veterinary , Chromatography, Thin Layer/methods , Chromatography, Thin Layer , Chromatography, Thin Layer/veterinary
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