A Mouse Model of Graded Contusive Spinal Cord Injury

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Abstract
A mouse model of spinal cord injury (SCI) could further increase our basic understanding of the mechanisms involved in injury and recovery by taking advantage of naturally-occurring and genetically engineered mutations available in mice. We have, therefore, investigated whether methods used to produce and evaluate graded experimental contusive SCI in the rat could be modified to produce a mouse model of traumatic SCI. C57BL6 mice were anesthetized with 2,2,2-tribromoethanol and a restricted laminectomy performed at the T8 vertebral level. The spinal column was stabilized and a weight drop technique used to produce contusive injury. Experimental groups were distinguished by the amount of weight or the height from which the weight was dropped onto an impounder resting on the dura (1 g × 2.5 cm, 2 g × 2.5 cm, 3 g × 2.5 cm, and 3 g × 5.0 cm). Functional deficits over time were examined up to 28 days after SCI by testing hindlimb reflex responses and coordinated motor function. Chronic lesion histopathology was evaluated by light microscopy and analyzed with morphometric techniques. All groups demonstrated profound functional deficits after injury followed by gradual recovery. Recovery correlated with the weight dropped and percent of white matter spared that was 41.3 ± 6.0% (mean ± SEM) in the 2 g × 2.5 cm group and 24.3 ± 5.0% in the 3 g × 2.5 cm group. A replicate experiment confirmed reproducibility of the injury. This new mouse model of contusive SCI could pave the way for in vivo studies of the effect of genetic modifications produced by specific mutations on injury and recovery processes after spinal cord trauma.