Improving the Efficiency and Efficacy of Glibenclamide in Limiting Progressive Hemorrhagic Necrosis Following Traumatic Spinal Cord Injury
Abstract
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 (n=36) 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).
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA599057
Entities
People
- Phillip G. Popovich
Organizations
- Ohio State University