Improving the Efficiency and Efficacy of Glibenclamide in Limiting Progressive Hemorrhagic Necrosis Following Traumatic Spinal Cord Injury

Preclinical work has demonstrated that glibenclamide administration improves outcomes in rat models of spinal cord injury, with the principal mechanism of action being amelioration of post-traumatic hemorrhagic necrosis PHN. We hypothesize that some but not all patients with spinal cord injury, principally those with incomplete lesions, will respond to glibenclamide therapy. Our goal is to determine whether MRI and circulating biomarkers can be used as early markers of injury that can be used to predict which patients may benefit from glibenclamide treatment. During the first year of this grant acute MRI images 6 and 24 hours post-injury were collected from n36 rats subject to spinal contusion injury. Both the severity and location of injury were changed to create six different experimental groups 1 Midline M severe 50 mm 2 M moderate 25 mm 3 M light 12.5 mm 4 Lateral L severe 50 mm 5 L moderate 25 mm and 6 L light 12.5 mm. Preliminary analyses of these data reveal that injury location and severity affect the rate and magnitude of secondary hemorrhage. In year 2, we compared the efficacy of glibenclamide in the two most consistent injury models i.e., groups 2 vs. 5 moderate midline vs. lateral SCI. Data from these studies were recently published and indicate that glibenclamide is beneficial in both models of cervical SCI however, the magnitude of benefit was greatest when the magnitude and extent of primary hemorrhage was limited during the first 24h i.e., moderate lateral SCI.