Journal
SCIENCE
Volume 344, Issue 6189, Pages 1250-1255Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1253050
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Funding
- European Union [201024, 223524]
- advanced European Research Council grant NOGORISE
- Swiss National Science Foundation [31-138676, 3100A0_12252711, 31003A_149858]
- Christopher and Dana Reeve Foundation
- Dr. Wilhelm Hurka Foundation
- German Excellence Initiative, Deutsche Forschungsgemeinschaft project [49/2]
- Grants-in-Aid for Scientific Research [25560436] Funding Source: KAKEN
- Swiss National Science Foundation (SNF) [31003A_149858] Funding Source: Swiss National Science Foundation (SNF)
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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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