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

2014; American Association for the Advancement of Science; Volume: 344; Issue: 6189 Linguagem: Inglês

10.1126/science.1253050

1095-9203

Anna-Sophia Wahl, Wolfgang Omlor, José C. Rubio, Jerry L. Chen, Hongwei Zheng, Aileen Schröter, Miriam Gullo, Oliver Weinmann, Kenta Kobayashi, Fritjof Helmchen, Björn Ommer, Martin E. Schwab,

Nerve injury and regeneration

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.