A New Acute Impact-Compression Lumbar Spinal Cord Injury Model in the Rodent

作者:Moonen Gray; Satkunendrarajah Kajana; Wilcox Jared T; Badner Anna; Mothe Andrea; Foltz Warren; Fehlings Michael G; Tator Charles H*
来源:Journal of Neurotrauma, 2016, 33(3): 278-289.
DOI:10.1089/neu.2015.3937

摘要

Traumatic injury to the lumbar spinal cord results in complex central and peripheral nervous tissue damage causing significant neurobehavioral deficits and personal/social adversity. Although lumbar cord injuries are common in humans, there are few clinically relevant models of lumbar spinal cord injury (SCI). This article describes a novel lumbar SCI model in the rat. The effects of moderate (20g), moderate-to-severe (26g) and severe (35g, and 56g) clip impact-compression injuries at the lumbar spinal cord level L1-L2 (vertebral level T11-T12) were assessed using several neurobehavioral, neuroanatomical, and electrophysiological outcome measures. Lesions were generated after meticulous anatomical landmarking using microCT, followed by laminectomy and extradural inclusion of central and radicular elements to generate a traumatic SCI. Clinically relevant outcomes, such as MR and ultrasound imaging, were paired with robust morphometry. Analysis of the lesional tissue demonstrated that pronounced tissue loss and cavitation occur throughout the acute to chronic phases of injury. Behavioral testing revealed significant deficits in locomotion, with no evidence of hindlimb weight-bearing or hindlimb-forelimb coordination in any injured group. Evaluation of sensory outcomes revealed highly pathological alterations including mechanical allodynia and thermal hyperalgesia indicated by increasing avoidance responses and decreasing latency in the tail-flick test. Deficits in spinal tracts were confirmed by electrophysiology showing increased latency and decreased amplitude of both sensory and motor evoked potentials (SEP/MEP), and increased plantar H-reflex indicating an increase in motor neuron excitability. This is a comprehensive lumbar SCI model and should be useful for evaluation of translationally oriented pre-clinical therapies.