RESUMEN
Stroke causes loss of neurological function. Recovery after stroke is facilitated by forced use of the affected limb and is associated with sprouting of new connections, a process that is sharply confined in the adult brain. We show that ephrin-A5 is induced in reactive astrocytes in periinfarct cortex and is an inhibitor of axonal sprouting and motor recovery in stroke. Blockade of ephrin-A5 signaling using a unique tissue delivery system induces the formation of a new pattern of axonal projections in motor, premotor, and prefrontal circuits and mediates recovery after stroke in the mouse through these new projections. Combined blockade of ephrin-A5 and forced use of the affected limb promote new and surprisingly widespread axonal projections within the entire cortical hemisphere ipsilateral to the stroke. These data indicate that stroke activates a newly described membrane-bound astrocyte growth inhibitor to limit neuroplasticity, activity-dependent axonal sprouting, and recovery in the adult.
Asunto(s)
Axones/metabolismo , Efrina-A5/metabolismo , Plasticidad Neuronal/fisiología , Recuperación de la Función/fisiología , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/fisiopatología , Animales , Astrocitos/metabolismo , Astrocitos/patología , Axones/patología , Conducta Animal , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Efrina-A5/antagonistas & inhibidores , Ratones , Ratones Endogámicos C57BL , Actividad Motora/fisiología , Red Nerviosa/fisiopatología , Fosforilación , Transducción de Señal , Coloración y EtiquetadoRESUMEN
Reliable quantitative analysis of white matter connectivity in the brain is an open problem in neuroimaging, with common solutions requiring tools for fiber tracking, tractography segmentation and estimation of intersubject correspondence. This paper proposes a novel, template matching approach to the problem. In the proposed method, a deformable fiber-bundle model is aligned directly with the subject tensor field, skipping the fiber tracking step. Furthermore, the use of a common template eliminates the need for tractography segmentation and defines intersubject shape correspondence. The method is validated using phantom DTI data and applications are presented, including automatic fiber-bundle reconstruction and tract-based morphometry.