Macrophages and Microglia Produce Local Trophic Gradients That Stimulate Axonal Sprouting Toward but Not beyond the Wound Edge.

Batchelor, P E; Porritt, M J; Martinello, P; Parish, C L; Liberatore, G T; Donnan, G A; Howells, D W

Batchelor, P E; Porritt, M J; Martinello, P; Parish, C L; Liberatore, G T; Donnan, G A; Howells, D W.

Afiliación

Batchelor PE; Departments of Medicine, Neurology, The University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, Victoria, 3084, Australia.

Mol Cell Neurosci ; 21(3): 436-53, 2002 Nov.

Article en En | MEDLINE | ID: mdl-12498785

RESUMEN

Following injury to the mammalian CNS, axons sprout in the vicinity of the wound margin. Growth then ceases and axons fail to cross the lesion site. In this study, using dopaminergic sprouting in the injured striatum as a model system, we have examined the relationship of periwound sprouting fibers to reactive glia and macrophages. In the first week after injury we find that sprouting fibers form intimate relationships with activated microglia as they traverse toward the wound edge. Once at the wound edge, complicated plexuses of fibers form around individual macrophages. Axons, however, fail to grow further into the interior of the wound despite the presence of many macrophages in this location. We find that the expression of BDNF by activated microglia progressively increases as the wound edge is approached, while GDNF expression by macrophages is highest at the immediate wound margin. In contrast, the expression of both factors is substantially reduced within the macrophage-filled interior of the wound. Our data suggest that periwound sprouting fibers grow toward the wound margin along an increasing trophic gradient generated by progressively microglial and macrophage activation. Once at the wound edge, sprouting ceases over macrophages at the point of maximal neurotrophic factor expression and further axonal growth into the relatively poor trophic environment of the wound core fails to occur.

Asunto(s)

Lesiones Encefálicas/metabolismo; Conos de Crecimiento/metabolismo; Macrófagos/metabolismo; Glicoproteínas de Membrana; Microglía/metabolismo; Factores de Crecimiento Nervioso/metabolismo; Regeneración Nerviosa/fisiología; Proteínas del Tejido Nervioso; Cicatrización de Heridas/fisiología; Animales; Lesiones Encefálicas/fisiopatología; Factor Neurotrófico Derivado del Encéfalo/genética; Proteínas de Transporte de Dopamina a través de la Membrana Plasmática; Factor Neurotrófico Derivado de la Línea Celular Glial; Proteína Ácida Fibrilar de la Glía/metabolismo; Conos de Crecimiento/ultraestructura; Inmunohistoquímica; Antígeno de Macrófago-1/metabolismo; Macrófagos/ultraestructura; Masculino; Proteínas de Transporte de Membrana/metabolismo; Ratones; Ratones Endogámicos C57BL; Microglía/ultraestructura; Microscopía Electrónica; Neostriado/citología; Neostriado/metabolismo; Factores de Crecimiento Nervioso/genética; Vías Nerviosas/lesiones; Vías Nerviosas/metabolismo; Vías Nerviosas/cirugía; Plasticidad Neuronal/fisiología; ARN Mensajero/metabolismo; Sustancia Negra/lesiones; Sustancia Negra/metabolismo; Sustancia Negra/cirugía

Buscar en Google

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cicatrización de Heridas / Lesiones Encefálicas / Glicoproteínas de Membrana / Microglía / Conos de Crecimiento / Macrófagos / Factores de Crecimiento Nervioso / Regeneración Nerviosa / Proteínas del Tejido Nervioso Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Mol Cell Neurosci Asunto de la revista: BIOLOGIA MOLECULAR / NEUROLOGIA Año: 2002 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos

Buscar en Google

Añadir a Mi BVS

Imprimir

XML

PubMed Links