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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 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.

Pubmed ID: 22837401


  • Overman JJ
  • Clarkson AN
  • Wanner IB
  • Overman WT
  • Eckstein I
  • Maguire JL
  • Dinov ID
  • Toga AW
  • Carmichael ST


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

August 14, 2012

Associated Grants

  • Agency: NINR NIH HHS, Id: K99-NR010797
  • Agency: NINDS NIH HHS, Id: NS045729
  • Agency: NINDS NIH HHS, Id: NS049041
  • Agency: NINDS NIH HHS, Id: NS061530-02
  • Agency: NCRR NIH HHS, Id: RR021813

Mesh Terms

  • Animals
  • Astrocytes
  • Axons
  • Behavior, Animal
  • Cerebral Cortex
  • Ephrin-A5
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity
  • Nerve Net
  • Neuronal Plasticity
  • Phosphorylation
  • Recovery of Function
  • Signal Transduction
  • Staining and Labeling
  • Stroke