Controlled Cortical Impact-induced Neurodegeneration Decreases after Administration of the Novel Calpain-inhibitor Gabadur

Authors

Rachelle Dugue
Getaw Hassen, New York Medical CollegeFollow
Abraham Shulman
Jeffrey H. Goodman
Hillary Michelson
Peter Serrano
Satendra Chauhan
Douglas S. F. Ling

DOI

10.1016/j.brainresbull.2018.08.016

Journal Title

Brain Research Bulletin

First Page

368

Last Page

373

Document Type

Article

Publication Date

8-1-2018

Department

Emergency Medicine

Keywords

Brain Injuries, Traumatic, Calpain, Leupeptins, Pregabalin, Time Factors

Disciplines

Medicine and Health Sciences | Therapeutics

Abstract

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.

Recommended Citation

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