Innovative mouse model mimicking human-like features of spinal cord injury: efficacy of Docosahexaenoic acid on acute and chronic phases

• Published in: Scientific reports 2019-06, Vol.9 (1), p.8883-16, Article 8883
• Main Authors: Marinelli, Sara, Vacca, Valentina, De Angelis, Federica, Pieroni, Luisa, Orsini, Tiziana, Parisi, Chiara, Soligo, Marzia, Protto, Virginia, Manni, Luigi, Guerrieri, Roberto, Pavone, Flaminia
• Format: Article
• Language: English
• Subjects: 13; 13/2; 13/51; 631/378/1687/1825; 631/378/1689/364; 64; 64/60; 82/80; 96; Acids; Acute Disease; Animals; Apoptosis; Chronic Disease; Demyelination; Disease Models, Animal; Docosahexaenoic acid; Docosahexaenoic Acids - therapeutic use; Female; Humanities and Social Sciences; Humans; Inflammation; Injuries; Mice; Mimicry; multidisciplinary; Neuroprotection; Paralysis; Proteomes; Science; Science (multidisciplinary); Social impact; Spinal cord injuries; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - pathology; Structure-function relationships; Thorax; Trauma
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-45037-x

Traumatic spinal cord injury has dramatic consequences and a huge social impact. We propose a new mouse model of spinal trauma that induces a complete paralysis of hindlimbs, still observable 30 days after injury. The contusion, performed without laminectomy and deriving from the pressure exerted directly on the bone, mimics more closely many features of spinal injury in humans. Spinal cord was injured at thoracic level 10 (T10) in adult anesthetized female CD1 mice, mounted on stereotaxic apparatus and connected to a precision impactor device. Following severe injury, we evaluated motor and sensory functions, and histological/morphological features of spinal tissue at different time points. Moreover, we studied the effects of early and subchronic administration of Docosahexaenoic acid, investigating functional responses, structural changes proximal and distal to the lesion in primary and secondary injury phases, proteome modulation in injured spinal cord. Docosahexaenoic acid was able i) to restore behavioural responses and ii) to induce pro-regenerative effects and neuroprotective action against demyelination, apoptosis and neuroinflammation. Considering the urgent health challenge represented by spinal injury, this new and reliable mouse model together with the positive effects of docosahexaenoic acid provide important translational implications for promising therapeutic approaches for spinal cord injuries.