A role for ephrin-A5 in axonal sprouting, recovery, and activity-dependent plasticity after stroke

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 cor...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2012-08, Vol.109 (33), p.13154-13155
Main Authors: Overman, Justine J., Clarkson, Andrew N., Wanner, Ina B., Overman, William T., Eckstein, Ilya, Maguire, Jaime L., Dinov, Ivo D., Toga, Arthur W., Carmichael, S. Thomas
Format: Article
Language:English
Subjects:
adults
Animals
astrocytes
Astrocytes - metabolism
Astrocytes - pathology
axons
Axons - metabolism
Axons - pathology
Behavior, Animal
Biological Sciences
brain
cell viability
Cerebral Cortex - pathology
Cerebral Cortex - physiopathology
cortex
Ephrin-A5 - antagonists & inhibitors
Ephrin-A5 - metabolism
Mice
Mice, Inbred C57BL
Motor ability
Motor Activity - physiology
Nerve Net - physiopathology
Neurochemistry
Neuronal Plasticity - physiology
neuroplasticity
Phosphorylation
PNAS Plus
PNAS PLUS (AUTHOR SUMMARIES)
Proteins
Recovery of Function - physiology
Signal Transduction
Staining and Labeling
Stroke
Stroke - metabolism
Stroke - physiopathology
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1204386109