When the spinal cord is injured by trauma, it is common to have internal bleeding within the spinal cord. The amount and extent of bleeding predict how well an individual will recover from spinal cord injury (SCI) -- the less bleeding the better. Therefore, it is important to understand why some spinal cord injuries cause more or less bleeding. Also, since bleeding occurs in almost every case of the most severe types of SCI, it is important to develop therapies that can limit bleeding within the spinal cord.

Recently, scientists have found that a drug, glibenclamide (Glib), can limit bleeding in some but not all spinal cord injuries created in rodent models of SCI. A goal of this research program is to determine why Glib works in some but not all cases of SCI. We will establish protocols that should allow clinicians to screen individual SCI patients very early after injury and determine whether they should receive Glib therapy, and whether they will respond favorably to this therapy. Because Glib is an FDA-approved drug that has been given to patients with diabetes for over 3 decades, it has already been proven to be safe. However, if we can determine how to predict when Glib will work after SCI, we can optimize recovery of SCI patients by developing personalized rehabilitation protocols. Indeed, if we know that Glib will reduce bleeding and preserve more spinal cord tissue, the range of function that will be preserved should increase. This opens new options of rehabilitation.

Data derived from these experiments will also improve the efficiency of clinical trial enrollment. Specifically, we will measure the "signature" of proteins in the blood (i.e. serum biomarkers) of animals and humans that can or cannot respond to Glib therapy. By understanding how the mix of proteins in the blood early after SCI (e.g., hours) relates to recovery at later times post-injury (months or years), we can increase the speed and efficiency of patient enrollment into clinical trials. This would save time and money and would require that fewer patients be enrolled for testing. If our proposed studies are successful, it would be possible to immediately design a clinical trial to test glibenclamide in spinal cord injured humans.