Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates.
Sci. Transl. Med.. 2015-08-26; 7(302): 302ra134-302ra134
DOI: 10.1126/scitranslmed.aac5811
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1. Sci Transl Med. 2015 Aug 26;7(302):302ra134. doi: 10.1126/scitranslmed.aac5811.
Pronounced species divergence in corticospinal tract reorganization and
functional recovery after lateralized spinal cord injury favors primates.
Friedli L(1), Rosenzweig ES(2), Barraud Q(1), Schubert M(3), Dominici N(4), Awai
L(3), Nielson JL(5), Musienko P(6), Nout-Lomas Y(7), Zhong H(8), Zdunowski S(8),
Roy RR(8), Strand SC(9), van den Brand R(1), Havton LA(10), Beattie MS(11),
Bresnahan JC(11), Bézard E(12), Bloch J(13), Edgerton VR(8), Ferguson AR(5), Curt
A(3), Tuszynski MH(14), Courtine G(15).
Author information:
(1)Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences,
Swiss Federal Institute of Technology (EPFL), 1015 Lausanne, Switzerland.
(2)Department of Neurosciences, University of California, San Diego, La Jolla, CA
92093-0662, USA.
(3)Spinal Cord Injury Center, Balgrist University Hospital, University of Zurich,
8008 Zurich, Switzerland.
(4)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.
(5)Department of Neurosurgery, University of California, San Francisco (UCSF),
San Francisco, CA 94122, USA.
(6)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.
(7)College of Veterinary Medicine and Biomedical Sciences, Colorado State
University, Fort Collins, CO 80521, USA.
(8)Department of Integrative Biology and Physiology and Brain Research Center,
University of California, Los Angeles (UCLA), Los Angeles, CA 900095-7246, USA.
(9)California National Primate Research Center, University of California, Davis,
Davis, CA 95616-8542, USA.
(10)Department of Neurology, David Geffen School of Medicine, UCLA, Los Angeles,
CA 90095-1769, USA.
(11)Brain and Spinal Injury Center, UCSF, San Francisco, CA 94110, USA.
(12)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293,
F-33000 Bordeaux, France. CNRS, Institut des Maladies Neurodégénératives, UMR
5293, F-33000 Bordeaux, France.
(13)Clinical Neuroscience, University Hospital of Vaud (CHUV), 1011 Lausanne,
Switzerland.
(14)Department of Neurosciences, University of California, San Diego, La Jolla,
CA 92093-0662, USA. Veterans Administration Medical Center, San Diego, CA 92161,
USA.
(15)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. .
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.
Copyright © 2015, American Association for the Advancement of Science.
DOI: 10.1126/scitranslmed.aac5811
PMCID: PMC5669362
PMID: 26311729 [Indexed for MEDLINE]