Abstract
Summary Statement
The mechanism of spinal cord injury varies across the human population and this may be important for the development of effective therapies. Therefore, detailed understanding of how variables such as impact velocity and depth affect cord tissue damage is important.
Introduction
Studies have shown an independent effect of impact velocity and depth on injury severity, thereby suggesting importance of the interaction between the two for spinal cord injury. This work examines both the individual and interactive effects of impact velocity and impact depth on demyelination, tissue sparing, and behavioural outcomes in the rat cervical spinal cord. It also aims to understand the contribution of the energy applied during impact, not only the impact factors. Decoupling the effects of these two impact parameters will help to describe the injury mechanism. Maximum principal strain has also been shown to be useful as a predictor for neural tissue damage in vivo and in finite element (FE) models. A better understanding of this relationship with experimental results may help to elucidate the mechanics of spinal cord injury.
Methods
In this study, 54 male Sprague-Dawley rats were given a contusion spinal cord injury at impact speeds of 8 mm/s, 80 mm/s, or 800 mm/s with depths of 0.9 mm or 1.5 mm. Animals recovered for 7 days followed by behavioural assessment and examination of the spinal cord tissue for demyelination and tissue sparing at 1 mm intervals, ±3 mm rostrocaudally to the epicentre.
In parallel, a previously developed finite element model of the rat spinal cord was used to examine the resulting maximum principal strains in the spinal cord for correlations with histological and mechanical impact data.
Results and discussion
Impact depth was a consistent factor in predicting axonal damage, tissue sparing, and the resulting behavioural deficit. Increased impact velocity resulted in significantly higher impact energies and measureable tissue damage at the 1.5 mm impact depth, but not at the 0.9 mm impact depth and is best displayed by the percentage of axon damage at the injury epicentre. Linear correlation analysis with FEA strain showed significant (p≪0.001) correlations with axonal damage in the ventral (R2=0.86) and lateral (R2=0.74) regions of the spinal cord and with white matter (R2=0.90) and grey matter (R2=0.76) sparing.
Discussion and Conclusion
The difference in injury severity to velocity at different impact depths identifies the existence of threshold interactions between the two impact factors. Beyond this point incremental increases in either velocity or depth are more likely to result in significantly increased impact energy and thus tissue damage and functional impairment. The relationship between the impact depth and velocity of injury demonstrated a more rate sensitive response to spinal cord tissue damage at the deep (1.5 mm) impact depth than at the shallow (0.9 mm) impact depth. Impact velocity also became quickly less significant than impact depth in determining tissue damage further from the epicentre. Furthermore, the results shown by this work extend the research identifying significant correlations between maximum principal strain and neurological tissue damage.
