Experimental Modeling of Spinal Cord Injury: Characterization of a Force-Defined Injury Device

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Abstract
We examined the ability of a novel spinal cord injury (SCI) device to produce graded morphological and behavioral changes in the adult rat following an injury at thoracic level 10 (T10). The injury device uses force applied to the tissue as the control variable rather than tissue displacement. This has the advantage of eliminating errors that may arise from tissue movement prior to injury. Three different injury severities, defined by the amount of force applied to the exposed spinal cord at T10 (100, 150, and 200 kdyn), were evaluated at two different survival times (7 and 42 d). Unbiased stereology was employed to evaluate morphological differences following the injury. Quantitative behavioral assessment employed the Basso, Beattie, and Bresnahan locomotive rating scale. There was a significant force-related decline in locomotive ability following the injury. Animals subjected to a 200-kdyn injury performed significantly worse than animals subjected to a 100- and 150-kdyn injury. The locomotor ability at different days post injury significantly correlated with the amount of force applied to the spinal cord. Statistical analysis revealed several significant force-related morphological differences following the injury. The greatest loss of white and gray matter occurred at the site of injury impact and extended in both a rostral and caudal direction. Animals subjected to the greatest force (200 kdyn) displayed the least amount of spared tissue at both survival times indicative of the most severe injury. The amount of spared tissue significantly correlated with the locomotor ability. This novel rodent model of SCI provides a significant improvement over existing devices for SCI by reducing variability with a constant preset force to define the injury.