Journal
NEUROTHERAPEUTICS
Volume 15, Issue 3, Pages 751-769Publisher
SPRINGER
DOI: 10.1007/s13311-017-0589-9
Keywords
Spinal cord injury; non human primate; behavior; MRI; histopathology; microglia
Funding
- Verticale
- Demain Debout Aquitaine
- LabeX NUMEV
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Spinal cord injuries (SCI) lead to major disabilities affecting > 2.5 million people worldwide. Major shortcomings in clinical translation result from multiple factors, including species differences, development of moderately predictive animal models, and differences in methodologies between preclinical and clinical studies. To overcome these obstacles, we first conducted a comparative neuroanatomical analysis of the spinal cord between mice, Microcebus murinus (a nonhuman primate), and humans. Next, we developed and characterized a new model of lateral spinal cord hemisection in M. murinus. Over a 3-month period after SCI, we carried out a detailed, longitudinal, behavioral follow-up associated with in vivo magnetic resonance imaging (H-1-MRI) monitoring. Then, we compared lesion extension and tissue alteration using 3 methods: in vivo H-1-MRI, ex vivo H-1-MRI, and classical histology. The general organization and glial cell distribution/morphology in the spinal cord of M. murinus closely resembles that of humans. Animals assessed at different stages following lateral hemisection of the spinal cord presented specific motor deficits and spinal cord tissue alterations. We also found a close correlation between H-1-MRI signal and microglia reactivity and/or associated post-trauma phenomena. Spinal cord hemisection in M. murinus provides a reliable new nonhuman primate model that can be used to promote translational research on SCI and represents a novel and more affordable alternative to larger primates.
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