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The effect of impact velocity on acute spinal cord injury Sparrey, Carolyn Jennifer

Abstract

Spinal cord injury is a devastating and catastrophic occurrence and effective comprehensive treatments have not yet been discovered. Contusion models of spinal cord injury are used in the evaluation of drug therapies and neuroprotection strategies and should mimic human injury. Existing models have focused on the significance of displacement and force as parameters of injury while the importance of impact velocity remains contentious. The objectives of this study were to install and calibrate a spinal cord contusion device, establish a protocol for its operation and to use the device to examine the effect of impact velocity on mechanical injury to the spinal cord using clinically relevant velocities. Contusion injuries were created using a modified Spinal Cord Injury Research System (Stokes et al. 1992). Male, Sprague-Dawley rats (210-320g) were injured at the T10 level. Deeply anaesthetized animals (n=31) were injured at slow (3mm/s) and fast (300mm/s) impact velocities to a depth of 1mm and then immediately sacrificed to assess the primary lesion. Sham control animals experienced the surgical procedure but were removed from the device without injury and sacrificed. The mechanical parameters of injury were assessed and Young's moduli were estimated for the injury groups. Cord sections were stained with haematoxylin and eosin (H&E) and the SMI32 antibody to non-phosphorylated neurofilament and the injury responses in the grey and white matter were analyzed. The results showed that the volume of haemorrhage in the white matter was a function of impact velocity (fast=0.61 mm³ , slow=0.24 mm³ , p=0.013) while the total haemorrhage volume (fast=1.51 mm³, slow=1.21 mm³ , p=0.22) showed no difference. The SMI32 reactivity showed a significant relationship between impact velocity and axonal damage (p=0.013). Complete axonal disruption was evident in the fast injury group around the injury epicentre. Post-hoc analyses revealed a significant difference between the fast and slow/control groups in the lateral-ventral white matter (p=0.001) and ventral white matter (p=0.035) but no observed effect between slow and control groups. Damage to the grey matter, as reflected by haemorrhage volume was similar between the slow and fast groups (fast = 0.89 mm³ , slow = 0.97 mm³) however analysis of grey matter reactivity to the SMI 32 antibody showed a significant effect of velocity (p = 0.03). A post-hoc analysis revealed significant differences between the fast and slow impact groups immediately (p = 0.04) and 1.5mm (p = 0.05) caudal to the injury site but rostral to the injury site the difference was not significant (p = 0.07). The mechanical response of the spinal cord to contusion injury demonstrated Young's moduli of 76 kPa for the slow injury and 298 kPa for the fast injury. We conclude that impact velocity has an effect on the magnitude of injury within the white matter during spinal cord injury and an effect on the amount of neuronal damage in the grey matter. The extent of haemorrhage in the grey matter appeared independent of impact velocity. The mechanical response of the tissue to injury showed a four-fold increase in the elastic modulus between the slow and fast groups. These results help isolate the extent of primary mechanical damage in SCI and will enable human injury to be more accurately modeled by utilizing clinically relevant impact velocities.

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