In Vivo Tissue-level Thresholds for Spinal Cord Injury

Primary damage to the blood-spinal cord barrier (BSCB) is a nearly universal consequence of spinal cord injury that contributes significantly to the overall pathology. We have characterized quantitatively the extent and severity of primary, physical disruption of the BSCB in adult rats five minutes and fifteen minutes after graded trauma induced with the Impactor weight drop model of spinal cord contusion. Animals were injured by dropping a 10g mass 12.5, 25, or 50mm (nlevel=8) on to the exposed mid-thoracic spinal cord. The volume of extravasation of three markers of distinct size – fluorescently labeled hydrazide (~730Da), fluorescently labeled bovine serum albumin (~70kDa), and immunohistochemically labeled red blood cells (~5μm dia) were quantified in both the gray and white matter. The results indicate that spinal cord trauma causes immediate, non-specific vascular changes that are well-predicted by mechanical parameters. Extravasation volume increased significantly with increasing drop height and decreasing marker size. Extravasation volumes for all three markers were greater in gray matter than in white matter, and were better correlated to the rate of spinal cord compression than to the depth of spinal cord compression, which suggests that tissue-level strain rate effects contribute to primary spinal cord microvasculature pathology. The relationship between the response of the spinal cord and the injury pattern points towards opportunities to control the distribution and extent of injury patterns in animal models of spinal cord injury through a precise understanding of model and tissue biomechanics, as well as potential improvements in means of preventing