A Novel Translational Model of Spinal Cord Injury in Nonhuman Primate

Neurotherapeutics. 2018 Jul;15(3):751-769. doi: 10.1007/s13311-017-0589-9.

Abstract

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 (1H-MRI) monitoring. Then, we compared lesion extension and tissue alteration using 3 methods: in vivo 1H-MRI, ex vivo 1H-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 1H-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.

Keywords: MRI; Spinal cord injury; behavior; histopathology; microglia; non human primate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Binding Proteins
  • Cheirogaleidae
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal*
  • Exploratory Behavior
  • Female
  • Follow-Up Studies
  • Functional Laterality
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Microfilament Proteins
  • Microglia / pathology
  • Middle Aged
  • Muscle Strength / physiology
  • Neuromuscular Junction / pathology
  • Psychomotor Performance / physiology
  • Species Specificity
  • Spinal Cord / pathology
  • Spinal Cord Injuries / pathology*
  • Spinal Cord Injuries / physiopathology*
  • Time Factors
  • Translational Medical Research / methods*
  • Tritium

Substances

  • AIF1 protein, human
  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Microfilament Proteins
  • Tritium