Blocking Ephrin-A5 Spurs Recovery from Stroke in Mouse Model

Neuroscience researchers have identified a novel molecule in the brain that retards recovery from stroke by blocking the formation of new connections between neurons.

Investigators at the University of California, Los Angeles (USA) were attracted by the indication of increased production of the growth inhibitor ephrin-A5 by brain cells after stroke in a mouse model.

Ephrin-A5 is a protein encoded by a member of the ephrin gene family that prevents axon bundling in co-cultures of cortical neurons with astrocytes, a model of late stage nervous system development and differentiation.

Results published in the July 25, 2012, online edition of the journal Proceedings of the National Academy of Sciences of the USA (PNAS) revealed that damage to the brain induced ephrin-A5 production in reactive astrocytes where it acted as an inhibitor of axonal sprouting and motor recovery. Blocking ephrin-A5 signaling using a unique tissue delivery system induced the formation of a new pattern of axonal projections in motor, premotor, and prefrontal circuits and mediated recovery after stroke in the mice through these new projections. Combined blockade of ephrin-A5 and forced use of the affected limb promoted new and surprisingly widespread axonal projections within the entire cortical hemisphere on the same side of the body as the stroke.

If duplicated in humans, drugs to block ephrin-A5 activity could pave the way for a more rapid recovery from stroke and may allow a synergy with existing treatments, such as physical therapy.

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