Immediate Damage to The Blood-Spinal Cord Barrier Due to Mechanical Trauma

Abstract

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, including the introduction of reactive species that induce cytotoxicity as well as secondary insults on the BSCB itself. We have characterized quantitatively the extent and severity of primary, physical disruption of the BSCB in adult rats 5 min after graded trauma induced with the Impactor weight-drop model of spinal cord contusion. Animals were injured by dropping a 10-g mass 12.5, 25, or 50 mm (n(level) = 8) on to the exposed mid-thoracic spinal cord. The volume of extravasation of three markers of distinct size--fluorescently labeled hydrazide ( approximately 730 Da), fluorescently labeled bovine serum albumin ( approximately 70 kDa), and immunohistochemically labeled red blood cells ( approximately 5 microm in diameter)--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 microvas…