Effect of Diazoxide and Dimethyl Sulfoxide on Behavioral Outcomes and Markers of Pathology Following Controlled Cortical Impact.

摘要

Traumatic brain injury (TBI) is a significant worldwide problem with an estimated incidence of at least 200 cases per 100,000 people per year. Due to recent military conflicts in the Middle East, a tremendous spike in the incidence of combat related brain injury has occurred over the past decade. Over the last 30 years, preclinical research focused on evaluating potential pharmacologic therapeutic agents has produced multiple promising candidates; however, to date no single drug intervention has consistently shown benefit when administered in the clinical setting. Fortunately, new potential therapeutic targets are being identified at a staggering rate as technology advances and our understanding of the pathology behind brain injury improves. In an effort to advance the therapeutic and molecular target realms of basic research, our team tested two hypotheses. First, that diazoxide (DZ), a putative mitochondrial KArP opener, administered after brain injury will result in short and long-term improvement in memory, motor, and behavioral function; and second, that moderate and severe traumatic brain injury will result in early and sustained widespread alterations of polysialylated neural cell adhesion molecule (PSA-NCAM) expression.