Research Article

Asynchronous therapy restores motor control by rewiring of the rat corticospinal tract after stroke

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Science  13 Jun 2014:
Vol. 344, Issue 6189, pp. 1250-1255
DOI: 10.1126/science.1253050

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Improving stroke recovery by timing treatment

Patients recovering from strokes often fight a long uphill battle, with mixed results. Studying the effect of physical training on regeneration from damaged nerves in a model of stroke in rats, Wahl et al. show that timing matters. First, the researchers gave the rats a stroke, which damaged their ability to reach for food pellets with their forelimbs. The researchers then gave them physical training and treated them with an antibody to encourage neural regeneration. The rats improved more when the researchers waited until after the antibody treatment to start the training. Damaged circuits, it seems, need a little time to regrow before being called into action.

Science, this issue p. 1250


The brain exhibits limited capacity for spontaneous restoration of lost motor functions after stroke. Rehabilitation is the prevailing clinical approach to augment functional recovery, but the scientific basis is poorly understood. Here, we show nearly full recovery of skilled forelimb functions in rats with large strokes when a growth-promoting immunotherapy against a neurite growth–inhibitory protein was applied to boost the sprouting of new fibers, before stabilizing the newly formed circuits by intensive training. In contrast, early high-intensity training during the growth phase destroyed the effect and led to aberrant fiber patterns. Pharmacogenetic experiments identified a subset of corticospinal fibers originating in the intact half of the forebrain, side-switching in the spinal cord to newly innervate the impaired limb and restore skilled motor function.

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