title: A Mouse Model of Bilateral Cervical Contusion-Compression Spinal Cord Injury.
abstract: Cervical spinal cord injury (cSCI) occurs in over half of all cases of traumatic spinal cord injury (SCI), yet we lack therapies that can generate significant functional recovery in these patients. The development of animal models of cSCI will aid in the pre-clinical assessment of therapies and in understanding basic pathophysiological mechanisms. Here, we describe a clinically relevant model of cervical contusion-compression injury in the mouse. Using a modified aneurysm clip, we generated a bilateral, incomplete injury that mimics contusion-compression injuries most commonly observed in humans. We followed the recovery of injured and sham-operated (laminectomy-only) animals for 8 weeks post-surgery. Behavioral tests, including the Basso Mouse Scale (BMS), wire hanging, grip strength, and CatWalk automated gait analysis, showed that while natural recovery is limited, it occurs in a clinically relevant window during the subacute phase of injury (7-14 days post-SCI). BMS scoring demonstrated that, while injured animals are ambulatory, they do not recover normal locomotor ability. CatWalk analysis quantitatively showed a loss of coordination and motor ability, with minimal recovery. The wire hanging and grip strength tests confirmed a significant decrease in forelimb motor strength in injured animals. Histological analysis carried out during the subacute phase (7-day time point) and chronic phase (8-week time point) demonstrated that the lesion epicenter is formed by 7 days post-SCI. Volumetric analysis of protein kinase C gamma (PKCgamma)-stained axons revealed that this injury results in significant damage to the corticospinal tract caudal to the injury site. Finally, we used quantitative real-time polymerase chain reaction to show that genes associated with inflammation and glial scarring are upregulated as a result of injury. This study confirms that we can effectively model bilateral cervical injury in the mouse and provides a framework for future studies using this model to assess therapies.
authors.affiliation: 1 Division of Genetics and Development, Toronto Western Research Institute, Krembil Neuroscience Center, University Health Network , Toronto, Ontario, Canada .
authors.forename: Nicole
authors.initials: N
authors.lastname: Forgione
authors.affiliation: 1 Division of Genetics and Development, Toronto Western Research Institute, Krembil Neuroscience Center, University Health Network , Toronto, Ontario, Canada .
authors.forename: Mahmood
authors.initials: M
authors.lastname: Chamankhah
authors.affiliation: 1 Division of Genetics and Development, Toronto Western Research Institute, Krembil Neuroscience Center, University Health Network , Toronto, Ontario, Canada .|2 Institute of Medical Sciences, Faculty of Medicine, University of Toronto , Toronto, Ontario, Canada .|3 Neuroscience Program, University of Toronto , Toronto, Ontario, Canada .|4 Department of Surgery, Division of Neurosurgery, University of Toronto , Toronto, Ontario, Canada .
authors.forename: Michael G
authors.initials: MG
authors.lastname: Fehlings
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003288:Contusions / Q000150:complications; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology*; D013117:Spinal Cord Compression / Q000150:complications; D013119:Spinal Cord Injuries / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*
keywords: models of injury; neural injury; spinal cord injury