Thomas P Davis
University of Missouri, USA
Our laboratory continues its long-term biodistribution/ pharmacokinetics research program, funded by N.I.H. continuously, since 1981, by studying mechanisms involved in delivering drugs across the blood-brain barrier (BBB) to the central nervous system (CNS) in pathological disease states. We have recently discovered that specific drug transporters are affected by pathologies such as the CNS hypoxia/reperfusion component of stroke and peripheral pain and, therefore, can be targeted to enhance delivery. We are also actively studying the effect of peripheral inflammatory pain and hypoxia/reoxygenation stress on paracellular permeability and tight junction organization at the BBB. We have recently shown that short-term hypoxic stress leads to significant alterations in BBB permeability that can be reversed by Tempol, a free radical scavenger, suggesting that oxidative stress plays a critical role in altering BBB functional integrity during pathophysiological insult. This work has significant consequences to the study of stroke. Additionally, we have shown that peripheral inflammatory pain has significant effects on BBB structure and function characterized by changes in oligomeric assemblies of the key tight junction protein occludin and altered functional expression of the drug efflux transporter P-glycoprotein.