Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates
Year: 2015
Type: article
Abstract: Experimental and clinical studies suggest that primate species exhibit greater recovery after lateralized compared to symmetrical spinal cord injuries. Although this observation has major implications for designing clinical trials and translational therapies, advantages in recovery of nonhuman primates over other species have not been shown statistically to date, nor have the associated repair mechanisms been identified. We monitored recovery in more than 400 quadriplegic patients and found that functional gains increased with the laterality of spinal cord damage. Electrophysiological analyses suggested that corticospinal tract reorganization contributes to the greater recovery after lateralized compared with symmetrical injuries. To investigate underlying mechanisms, we modeled lateralized injuries in rats and monkeys using a lateral hemisection, and compared anatomical and functional outcomes with patients who suffered similar lesions. Standardized assessments revealed that monkeys and humans showed greater recovery of locomotion and hand function than did rats. Recovery correlated with the formation of corticospinal detour circuits below the injury, which were extensive in monkeys but nearly absent in rats. Our results uncover pronounced interspecies differences in the nature and extent of spinal cord repair mechanisms, likely resulting from fundamental differences in the anatomical and functional characteristics of the motor systems in primates versus rodents. Although rodents remain essential for advancing regenerative therapies, the unique response of the primate corticospinal tract after injury reemphasizes the importance of primate models for designing clinically relevant treatments.
Source: Science Translational Medicine
Authors: Lucia Friedli, Ephron S. Rosenzweig, Quentin Barraud, Martin Schubert, Nadia Dominici, Lea Awai, Jessica L. Nielson, Pavel Musienko, Yvette Nout-Lomas, Hui Zhong, Sharon Zdunowski, Roland R. Roy, Sarah C. Strand, Rubia van den Brand, Leif A. Havton, Michael S. Beattie, Jacqueline C. Bresnahan, Erwan Bézard, Jocelyne Bloch, V. Reggie Edgerton, Adam R. Ferguson, Armin Curt, Mark H. Tuszynski, Grégoire Courtine
Institutions: École Polytechnique Fédérale de Lausanne, University of California San Diego, University of Zurich, Universitätsklinik Balgrist, Amsterdam Movement Sciences, Vrije Universiteit Amsterdam, University of California, San Francisco, St Petersburg University, Colorado State University, University of California, Los Angeles, University of California, Davis, Centre National de la Recherche Scientifique, Université de Bordeaux, Institut des Maladies Neurodégénératives, Centre Hospitalier Universitaire Vaudois, United States Department of Veterans Affairs
Language: English
Topic: Spinal Cord Injury Research
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: National Science Foundation, Craig H. Neilsen Foundation, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Russian Science Foundation, National Institutes of Health, Seventh Framework Programme, National Institute of Neurological Disorders and Stroke
Awards: G1310842400, G1589084597, Combinatorial Approaches to SCI, Plasticity and Regeneration in the Primate Spinal Cord, Plasticity and Regeneration in the Primate Spinal Cord, G3499436710, MINORITY PREDOCTORAL FELLOWSHIP PROGRAM--NIGMS, G4005226305, G4387770644, Bioinformatics For Translational Spinal Cord Injury Research, Restoring supraspinal control of locomotion after severe and chronic spinal cord injury, Translational outcome measures of cervical spinal cord injury, G757766735, G811196399, G8302189003, G9000083930
OpenAlex ID: W2134705330