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The Journal of Neuroscience, September 17, 2008, 28(38):9386-9403; doi:10.1523/JNEUROSCI.1697-08.2008

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Development/Plasticity/Repair
Constraint-Induced Movement Therapy in the Adult Rat after Unilateral Corticospinal Tract Injury

Irin C. Maier,^1,2 Kaspar Baumann,^1,2 Michaela Thallmair,^1,2 Oliver Weinmann,^1,2 Jeannette Scholl,^1,2 and Martin E. Schwab^1,2

¹Brain Research Institute, University of Zurich, and ²Department of Biology, Swiss Federal Institute of Technology, 8057 Zurich, Switzerland

Correspondence should be addressed to Irin C. Maier, Brain Research Institute, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Email: imaier{at}hifo.uzh.ch

Smaller spinal cord injuries often allow some degree of spontaneous behavioral improvements because of structural rearrangements within different descending fiber tracts or intraspinal circuits. In this study, we investigate whether rehabilitative training of the forelimb (forced limb use) influences behavioral recovery and plastic events after injury to a defined spinal tract, the corticospinal tract (CST). Female adult Lewis rats received a unilateral CST injury at the brainstem level. Use of the contralateral impaired forelimb was either restricted, by a cast, or forced, by casting the unimpaired forelimb immediately after injury for either 1 or 3 weeks. Forced use of the impaired forelimb was followed by full behavioral recovery on the irregular horizontal ladder, whereas animals that could not use their affected side remained impaired. BDA (biotinylated dextran amine) labeling of the intact CST showed lesion-induced growth across the midline where CST collaterals increased their innervation density and extended fibers toward the ventral and the dorsal horn in response to forced limb use. Gene chip analysis of the denervated ventral horn revealed changes in particular for growth factors, adhesion and guidance molecules, as well as components of synapse formation suggesting an important role for these factors in activity-dependent intraspinal reorganization after unilateral CST injury.

Key words: corticospinal tract; forced limb use; spinal cord injury; plasticity; rehabilitation; activity

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Received April 18, 2008; revised June 26, 2008; accepted Aug. 6, 2008.

Correspondence should be addressed to Irin C. Maier, Brain Research Institute, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Email: imaier{at}hifo.uzh.ch

This article has been cited by other articles:

				M. Brus-Ramer, J. B. Carmel, and J. H. Martin Motor Cortex Bilateral Motor Representation Depends on Subcortical and Interhemispheric Interactions J. Neurosci., May 13, 2009; 29(19): 6196 - 6206. [Abstract] [Full Text] [PDF]

				The Neuroscientist Comments: Comments Neuroscientist, February 1, 2009; 15(1): 7 - 8. [PDF]

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