title: Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates.
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.
authors: Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland.
authors: Lucia
authors: L
authors: Friedli
authors: Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0662, USA.
authors: Ephron S
authors: ES
authors: Rosenzweig
authors: Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland.
authors: Quentin
authors: Q
authors: Barraud
authors: Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, 8008 Zurich, Switzerland.
authors: Martin
authors: M
authors: Schubert
authors: Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland. MOVE Research Institute Amsterdam, Faculty of Human Movement Sciences, VU University Amsterdam, 1081 BT Amsterdam, Netherlands.
authors: Nadia
authors: N
authors: Dominici
authors: Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, 8008 Zurich, Switzerland.
authors: Lea
authors: L
authors: Awai
authors: Department of Neurosurgery, University of California, San Francisco (UCSF), San Francisco, CA 94122, USA.
authors: Jessica L
authors: JL
authors: Nielson
authors: Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland. Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia.
authors: Pavel
authors: P
authors: Musienko
authors: College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80521, USA.
authors: Yvette
authors: Y
authors: Nout-Lomas
authors: Department of Integrative Biology and Physiology and Brain Research Center, University of California, Los Angeles (UCLA), Los Angeles, CA 900095-7246, USA.
authors: Hui
authors: H
authors: Zhong
authors: Department of Integrative Biology and Physiology and Brain Research Center, University of California, Los Angeles (UCLA), Los Angeles, CA 900095-7246, USA.
authors: Sharon
authors: S
authors: Zdunowski
authors: Department of Integrative Biology and Physiology and Brain Research Center, University of California, Los Angeles (UCLA), Los Angeles, CA 900095-7246, USA.
authors: Roland R
authors: RR
authors: Roy
authors: California National Primate Research Center, University of California, Davis, Davis, CA 95616-8542, USA.
authors: Sarah C
authors: SC
authors: Strand
authors: Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland.
authors: Rubia
authors: R
authors: van den Brand
authors: Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-1769, USA.
authors: Leif A
authors: LA
authors: Havton
authors: Brain and Spinal Injury Center, UCSF, San Francisco, CA 94110, USA.
authors: Michael S
authors: MS
authors: Beattie
authors: Brain and Spinal Injury Center, UCSF, San Francisco, CA 94110, USA.
authors: Jacqueline C
authors: JC
authors: Bresnahan
authors: Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France. CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
authors: Erwan
authors: E
authors: Bézard
authors: Clinical Neuroscience, University Hospital of Vaud (CHUV), 1011 Lausanne, Switzerland.
authors: Jocelyne
authors: J
authors: Bloch
authors: Department of Integrative Biology and Physiology and Brain Research Center, University of California, Los Angeles (UCLA), Los Angeles, CA 900095-7246, USA.
authors: V Reggie
authors: VR
authors: Edgerton
authors: Department of Neurosurgery, University of California, San Francisco (UCSF), San Francisco, CA 94122, USA.
authors: Adam R
authors: AR
authors: Ferguson
authors: Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich, 8008 Zurich, Switzerland.
authors: Armin
authors: A
authors: Curt
authors: Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0662, USA. Veterans Administration Medical Center, San Diego, CA 92161, USA.
authors: Mark H
authors: MH
authors: Tuszynski
authors: Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland. Clinical Neuroscience, University Hospital of Vaud (CHUV), 1011 Lausanne, Switzerland. gregoire.courtine@epfl.ch.
authors: Grégoire
authors: G
authors: Courtine
mesh_terms: D000818:Animals; D007839:Functional Laterality; D000882:Haplorhini; D006801:Humans; D011712:Pyramidal Tracts / Q000473:pathology*; D051381:Rats; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000534:rehabilitation