Investigation of Novel Therapeutic for Physiological Deficits in a Post-Stroke Model

Brandon Moore*, Michael Watcher*, Pushkar Saralkar, Jacob Boos and Werner Geldenhuys, Department of Neuroscience, West Virginia University School of Medicine, Morgantown, WV 26506

Field (Broad Category): Neuroscience (Health Sciences) 

Student’s Major: Exercise Physiology 

Stroke is a detrimental condition caused by a lack of oxygen and nutrients to cerebral tissue ultimately leading to severe mental deficits, physical deficits, and even death. Ischemic strokes, resulting from occlusion of cerebral blood flow, have the highest incidence rate within the stroke population. The lack of oxygen seen in these patients leads to mitochondrial dysfunction, accumulation of reactive oxygen species (ROS), and a resultant increase in neuronal damage and death. MitoNEET (cisd1) is an outer mitochondrial membrane protein that has shown to have implications in regulating oxidative stress and has been successfully targeted in previous studies using thiazolidinedione (TZD)-class drugs. The role of mitoNEET in oxidative stress regulation post-stroke, however, has yet to be elucidated from the current literature. In this study, an in vivo ischemic-reperfusion stroke model using Caenorhibditis elegans was utilized to test the importance of mitoNEET and the effects of a mitoNEET-binding TZD-class drug on ROS accumulation in both wild-type and mitoNEET-knockout C. elegans. Survival and physiological functions including pharyngeal pumping rates, motility, and ROS production were used to assess effectiveness of treatment post-stroke. The data collected from this study suggest that post-stroke treatment with our novel TZD-class compound improves survival and physiological function compared to controls, thus providing data on a new alternative treatment following incidents of ischemic stroke. 

Funding: National Institutes of Health 

Program/mechanism supporting research/creative efforts: WVU 497-level course