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1.
J Neuroinflammation ; 12: 161, 2015 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-26338007

RESUMEN

BACKGROUND: The NG2 proteoglycan is expressed by several cell types in demyelinated lesions and has important effects on the biology of these cells. Here we determine the cell-type-specific roles of NG2 in the oligodendrocyte progenitor cell (OPC) and myeloid cell contributions to demyelination and remyelination. METHODS: We have used Cre-Lox technology to dissect the cell-type-specific contributions of NG2 to myelin damage and repair. Demyelination is induced by microinjection of 1 % lysolecithin into the spinal cord white matter of control, OPC-specific NG2-null (OPC-NG2ko), and myeloid-specific NG2-null (My-NG2ko) mice. The status of OPCs, myeloid cells, axons, and myelin is assessed by light, immunofluorescence, confocal, and electron microscopy. RESULTS: In OPC-NG2ko mice 1 week after lysolecithin injection, the OPC mitotic index is reduced by 40 %, resulting in 25 % fewer OPCs at 1 week and a 28 % decrease in mature oligodendrocytes at 6 weeks post-injury. The initial demyelinated lesion size is not affected in OPC-NG2ko mice, but lesion repair is delayed by reduced production of oligodendrocytes. In contrast, both the initial extent of demyelination and the kinetics of lesion repair are decreased in My-NG2ko mice. Surprisingly, the OPC mitotic index at 1 week post-injury is also reduced (by 48 %) in My-NG2ko mice, leading to a 35 % decrease in OPCs at 1 week and a subsequent 34 % reduction in mature oligodendrocytes at 6 weeks post-injury. Clearance of myelin debris is also reduced by 40 % in My-NG2ko mice. Deficits in myelination detected by immunostaining for myelin basic protein are confirmed by toluidine blue staining and by electron microscopy. In addition to reduced myelin repair, fewer axons are found in 6-week lesions in both OPC-NG2ko and My-NG2ko mice, emphasizing the importance of myelination for neuron survival. CONCLUSIONS: Reduced generation of OPCs and oligodendrocytes in OPC-NG2ko mice correlates with reduced myelin repair. Diminished demyelination in My-NG2ko mice may stem from a reduction (approximately 70 %) in myeloid cell recruitment to lesions. Reduced macrophage/microglia numbers may then result in decreased myelin repair via diminished clearance of myelin debris and reduced stimulatory effects on OPCs.


Asunto(s)
Antígenos/metabolismo , Enfermedades Autoinmunes Desmielinizantes SNC/patología , Células Mieloides/patología , Oligodendroglía/patología , Proteoglicanos/metabolismo , Recuperación de la Función/fisiología , Médula Espinal/patología , Animales , Antígenos/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Trasplante de Médula Ósea , Proteínas de Unión al Calcio/metabolismo , Diferenciación Celular/fisiología , Enfermedades Autoinmunes Desmielinizantes SNC/inducido químicamente , Enfermedades Autoinmunes Desmielinizantes SNC/cirugía , Modelos Animales de Enfermedad , Lisofosfatidilcolinas/toxicidad , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas de Microfilamentos/metabolismo , Vaina de Mielina/metabolismo , Vaina de Mielina/patología , Vaina de Mielina/ultraestructura , Células Mieloides/ultraestructura , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Factor de Transcripción 2 de los Oligodendrocitos , Oligodendroglía/metabolismo , Fagocitosis/fisiología , Proteoglicanos/genética , Células Madre/metabolismo , Células Madre/ultraestructura
2.
Eur J Neurosci ; 20(5): 1205-10, 2004 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15341592

RESUMEN

Mutant mice deficient in the myelin-associated glycoprotein (MAG) and the nonreceptor-type tyrosine kinase Fyn are characterized by a severely hypomyelinated central nervous system (CNS) and morphologically abnormal myelin sheaths. Despite this pronounced phenotype, MAG/Fyn-deficient mice have a normal longevity. In the present study, we took advantage of the normal life expectancy of this myelin mutant and grafted neural stem cells (NSCs) into the CNS of MAG/Fyn-deficient mice to study in short- and long-term experiments the fate of NSCs in adult dysmyelinated brains. Neural stem cells were isolated from spinal cords of transgenic mouse embryos ubiquitously expressing enhanced green fluorescent protein. Cells were expanded in vitro in the presence of mitogens for up to 5 weeks before they were grafted into the lateral ventricles or injected into white matter tracts. Analysis of mutant brains 3-15 weeks after intracerebroventricular transplantation of NSCs revealed only limited integration of donor cells into the host brains. However, injection of NSCs directly into white matter tracts resulted in widespread distribution of donor cells within the host tissue. Donor cells survived for at least 15 weeks in adult host brains. The majority of grafted cells populated white matter tracts and differentiated into oligodendrocytes that myelinated host axons. Results suggest that intraparenchymal transplantation of NSCs might be a strategy to reconstruct myelin in dysmyelinated adult brains.


Asunto(s)
Trasplante de Tejido Encefálico/métodos , Diferenciación Celular/fisiología , Enfermedades Autoinmunes Desmielinizantes SNC/metabolismo , Enfermedades Autoinmunes Desmielinizantes SNC/cirugía , Trasplante de Tejido Fetal/métodos , Neuronas/trasplante , Trasplante de Células Madre/métodos , Animales , Encéfalo/metabolismo , Encéfalo/cirugía , Trasplante de Tejido Encefálico/fisiología , Células Cultivadas , Enfermedades Autoinmunes Desmielinizantes SNC/genética , Femenino , Trasplante de Tejido Fetal/fisiología , Ratones , Ratones Transgénicos , Glicoproteína Asociada a Mielina/deficiencia , Glicoproteína Asociada a Mielina/genética , Embarazo , Proteínas Proto-Oncogénicas/deficiencia , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-fyn
3.
Rev. neurol. (Ed. impr.) ; 49(4): 176-180, 16 ago., 2009. tab, graf
Artículo en Español | IBECS (España) | ID: ibc-94809

RESUMEN

Objetivo. Determinar los factores de riesgo para recurrencia de convulsiones y la clasificación posquirúrgica a corto plazo en pacientes operados por esclerosis mesial temporal (EMT). Sujetos y métodos. Estudio de casos y controles anidado en la cohorte de pacientes con EMT diagnosticados por resonancia magnética con dos años de seguimiento posquirúrgico; se excluyeron pacientes con EMT bilateral. Se evaluaron características clínicas prequirúrgicas, foco epileptogénico en videoelectroencefalograma (video-EEG) y variables quirúrgicas con respecto a recurrencia de convulsiones en los primeros dos años tras la intervención y clasificación de Engel en el primer y segundo aniversario de la cirugía. Resultados. Entre octubre de 2001 y junio de 2008 se evaluó a 144 pacientes con EMT candidatos a cirugía de epilepsia; hasta junio de 2007, se había operado a 89 pacientes, un 51,7% con EMT izquierda. El 35,8% de los pacientes presentó recurrencia de convulsiones antes del segundo año tras la intervención; el factor de riesgo prequirúrgico asociado a recurrencia fue foco bitemporal o temporal único con diseminación contralateral por video-EEG (odds ratio = 6,32; intervalo de confianza al 95% = 1,64- 26,41); y el posquirúrgico, la presencia de convulsiones durante el primer mes tras la operación (p = 0,0004); no se encontró asociación con recurrencia para género, convulsiones tonicoclónicas generalizadas prequirúrgicas, lado de la EMT ni tiempo de evolución prequirúrgica de la epilepsia. El 66,3 y el 75,8% de los pacientes estaban en Engel I al primer y segundo año de la cirugía, respectivamente. El 91% de los pacientes intervenidos estaba en buen pronóstico posquirúrgico a los dos años. onclusión. La localización del foco epileptogénico por electrofisiología es un factor determinante en el pronóstico posquirúrgico a corto plazo en la EMT (AU)


Aim. To establish risk factors for seizure recurrence and short term Engel classification after surgery for mesial temporal sclerosis (MTS). Patients and methods. Nested case-control study in a cohort of patients diagnosed with MTS by magnetic resonance imaging and who had at least two years of postsurgical follow-up; patients with bilateral MTS were excluded. Clinical characteristics, epileptogenic focus in video-electroencefalography (video-EEG) and surgical issues were evaluated regarding to seizure recurrence during the first two postsurgical years and Engel classification in the first and second anniversary after surgery. Results. From October 2001 to June 2008, 144 patients with MTS were evaluated as candidates for epilepsy surgery; until June 2007, 89 patients underwent epilepsy surgery, 51.7% with left MTS. 35.8% of patients experienced seizure recurrence before two post-surgical years; presurgical risk factor associated to this recurrence was bitemporal focus or single temporal focus with contralateral dissemination by video-EEG (odds ratio = 6.32; 95% confidence interval = 1.64-26.41); and post-surgical, seizures that occurred in the first month of surgery (p = 0004). No association with seizure recurrence was found with gender, presurgical tonic-clonic seizures, MTS side and epilepsy duration. 66.3% and 75.8% of patients were Engel I classified in the first and second anniversary after surgery, respectively. 91% of operated patients showed a good outcome after two years of epilepsy surgery. Conclusion. Epileptogenic focus location by electrophysiology is a fundamental factor in short term outcome after surgery for MTS (AU)


Asunto(s)
Humanos , Convulsiones/epidemiología , Enfermedades Autoinmunes Desmielinizantes SNC/cirugía , Epilepsia del Lóbulo Temporal/cirugía , Factores de Riesgo , Recurrencia , Estudios Retrospectivos
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