Controlled Cortical Impact-induced Neurodegeneration Decreases after Administration of the Novel Calpain-inhibitor Gabadur
One aspect of secondary injury in traumatic brain injury is the marked increase in intracellular calcium and resultant over-activation of the calcium-dependent neutral cysteine protease calpain. Gabadur is a novel protease inhibitor with calpain-inhibition properties formulated from the classic protease inhibitor leupeptin linked to a pregabalin carrier. This construction allows the entire compound to cross the blood-brain barrier after peripheral administration to better target the site of injury. In this study, a single intraperitoneal dose of Gabadur was administered immediately following controlled cortical impact injury in rats. Neocortical slices were examined at 48 hours post-injury via Fluoro-Jade B staining, revealing an improvement in cortical neurodegeneration in Gabadur treated rats. Levels of detrimental active calpain-2 measured via western blot were also decreased in rats receiving Gabadur. This data supports the benefit of targeted protease inhibition in the treatment of traumatic brain injury.
Dugue, R., Hassen, G., Shulman, A., Goodman, J., Michelson, H., Serrano, P., Chauhan, S., & Ling, D. (2018). Controlled Cortical Impact-induced Neurodegeneration Decreases after Administration of the Novel Calpain-inhibitor Gabadur. Brain Research Bulletin, 142, 368-373. https://doi.org/10.1016/j.brainresbull.2018.08.016