title: Neuronal repair. Asynchronous therapy restores motor control by rewiring of the rat corticospinal tract after stroke.
abstract: 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.
authors.affiliation: Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland. Brain Research Institute, University of Zurich, Zurich, Switzerland. schwab@hifo.uzh.ch wahl@hifo.uzh.ch.
authors.forename: A S
authors.initials: AS
authors.lastname: Wahl
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.
authors.forename: W
authors.initials: W
authors.lastname: Omlor
authors.affiliation: Computer Vision Group, Heidelberg Collaboratory for Image Processing and Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Heidelberg, Germany.
authors.forename: J C
authors.initials: JC
authors.lastname: Rubio
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.
authors.forename: J L
authors.initials: JL
authors.lastname: Chen
authors.affiliation: Computer Vision Group, Heidelberg Collaboratory for Image Processing and Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Heidelberg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Institute for Biomedical Engineering, ETH Zurich, Zurich, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Schröter
authors.affiliation: Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland. Brain Research Institute, University of Zurich, Zurich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Gullo
authors.affiliation: Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland. Brain Research Institute, University of Zurich, Zurich, Switzerland.
authors.forename: O
authors.initials: O
authors.lastname: Weinmann
authors.affiliation: National Institute for Physiological Sciences, National Institute of Natural Sciences Myodaiji, Okazaki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Brain Research Institute, University of Zurich, Zurich, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Helmchen
authors.affiliation: Computer Vision Group, Heidelberg Collaboratory for Image Processing and Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Heidelberg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Ommer
authors.affiliation: Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland. Brain Research Institute, University of Zurich, Zurich, Switzerland. schwab@hifo.uzh.ch wahl@hifo.uzh.ch.
authors.forename: M E
authors.initials: ME
authors.lastname: Schwab
mesh_terms: D000818:Animals; D005260:Female; D007167:Immunotherapy / Q000379:methods; D009044:Motor Cortex / Q000503:physiopathology*; D009185:Myelin Proteins / Q000037:antagonists & inhibitors*; D000070798:Nogo Proteins; D010805:Physical Conditioning, Animal; D016548:Prosencephalon / Q000503:physiopathology; D011712:Pyramidal Tracts / Q000293:injuries* / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D020127:Recovery of Function; D000071939:Stroke Rehabilitation
chemical_list: D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat