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Neurite growth inhibitors restrict plasticity and functional recovery following corticospinal tract lesions

Nature Neuroscience volume 1, pages 124–131 (1998)Cite this article

A Correction to this article was published on 01 August 1998

Abstract

Anatomical plasticity and functional recovery after lesions of the rodent corticospinal tract (CST) decrease postnatally in parallel with myelin formation. Myelin-associated neurite growth inhibitory proteins prevent regenerative fiber growth, but whether they also prevent reactive sprouting of unlesioned fibers is less clear. Here we show that after unilateral CST lesion in the adult rat brainstem, both intact and lesioned tracts show topographically appropriate sprouting after treatment with a monoclonal antibody that neutralizes these inhibitory proteins. Antibody-treated animals showed full recovery in motor and sensory tests, whereas untreated lesioned rats exhibited persistent severe deficits. Neutralization of myelin-associated neurite growth inhibitors thus restores in adults the structural plasticity and functional recovery normally found only at perinatal ages.

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Figure 1: Treatment with IN-1 increases lesion-induced sprouting of the intact CST, as revealed by the increased number of fibers crossing the spinal cord midline.
Figure 2: Corticobulbar axons establish a bilateral projection in the red nucleus and pons after unilateral pyramidotomy and treatment with IN-1.
Figure 3: Treatment with IN-1 induces a partial reinnervation of the dorsal column nuclei after pyramidotomy.
Figure 4: Schematic representation of the lesion site and the corticospinal projections that were examined in this study.
Figure 5: The monoclonal antibody IN-1 leads to functional recovery in the food-pellet reaching task.
Figure 6: Treatment with IN-1 improves performance in the sticky-paper and rope-climbing tests.
Figure 7: Footprint analysis: angle of forelimb rotation.

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Acknowledgements

We thank Regula Schneider, Ruedi Kägi and Martina Weber for technical assistance. Roland Schoeb helped with photography and Eva Hochreutener with the graphics. This work was supported by the Swiss National Science Foundation, the International Research Institute of Paraplegia (Zürich) and the American Paralysis Association (Springfield, New Jersey).

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  1. Gwendolyn L. Kartje

    Present address: Neurology Service, Edward Hines Jr. Veterans Affairs Hospital, Hines, Illinois, 60141

Authors and Affiliations

  1. Brain Research Institute, University of Zürich and Swiss Federal Institute of Technology Zürich, August-Forel-Str. 1, Zürich, CH - 8029, Switzerland

    Michaela Thallmair, Gerlinde A. S. Metz, Werner J. Z'Graggen, Olivier Raineteau, Gwendolyn L. Kartje & Martin E. Schwab

  2. Departments of Neurology and Cell Biology, Neurobiology and Anatomy, Loyola University, Maywood, Illinois, 60153, USA

    Gwendolyn L. Kartje

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Thallmair, M., Metz, G., Z'Graggen, W. et al. Neurite growth inhibitors restrict plasticity and functional recovery following corticospinal tract lesions. Nat Neurosci 1, 124–131 (1998). https://doi.org/10.1038/373

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