Temporal Progression of Acute Spinal Cord Injury Mechanisms in a Rat Model: Contusion, Dislocation, and Distraction
Stephen Mattucci, Jason Speidel, Jie Liu, Wolfram Tetzlaff, Thomas R Oxland
Traumatic spinal cord injuries (SCIs) occur due to different spinal column injury patterns, including burst fracture, dislocation, and flexion–distraction. Pre-clinical studies modeling different SCI mechanisms have shown distinct histological differences between these injuries both acutely (3 h and less) and chronically (8 weeks), but there remains a temporal gap. Different rates of injury progression at specific regions of the spinal cord may provide insight into the pathologies that are initiated by specific SCI mechanisms. Therefore, the objective of this study was to evaluate the temporal progression of injury at specific tracts within the white matter, for time-points of 3 h, 24 h, and 7 days, for three distinct SCI mechanisms. In this study, 96 male Sprague Dawley rats underwent one of three SCI mechanisms: contusion, dislocation, or distraction. Animals were sacrificed at one of three times post-injury: 3 h, 24 h, or 7 days. Histological analysis using eriochrome cyanide and immunostaining for MBP, SMI-312, neurofilament-H (NF-H), and β-III tubulin were used to characterize white matter sparing and axon and myelinated axon counts. The regions analyzed were the gracile fasciculus, cuneate fasciculus, dorsal corticospinal tract, and ventrolateral white matter. Contusion, dislocation, and distraction SCIs demonstrated distinct damage patterns that progressed differently over time. Myelinated axon counts were significantly reduced after dislocation and contusion injuries in most locations and time-points analyzed (compared with sham). This indicates early myelin damage often within 3 h. Myelinated axon counts after distraction dropped early and did not demonstrate any significant progression over the next 7 days. Important differences in white matter degeneration were identified between injury types, with distraction injuries showing the least variability across time-points These findings and the observation that white matter injury occurs early, and in many cases, without much dynamic change, highlight the importance of injury type in SCI research—both clinically and pre-clinically.