2016 DIG Research Project | “Argon as a Potential Therapeutic in Stroke; Effects on Oxygen Utilization and Cerebral Blood Flow Response after Cortical Spreading Depression and Injury Depolarizations”
Background
Dr. Ulrike Hoffmann grew up in East Germany and moved with her family to West Germany in 1989, before the fall of the Berlin Wall. She attended medical school at The Charité, a large teaching hospital in Berlin that is affiliated with both Humboldt University and Freie Universität Berlin. While attending The Charité, she met Professor Uwe Heinemann in the Institute of Neurophysiology Charité Berlin and developed an interest in his research, which focused on spreading depolarizations in the developing brain after prolonged treatment with high concentrations of oxygen. Professor Heinemann became a lifelong mentor to Dr. Hoffmann and fortified her fascination to neurophysiology and electrophysiology.
Upon the completion of her medical degree and doctoral thesis in 2004, Dr. Hoffmann moved from Berlin to Bavaria, Germany to begin her residency in anesthesiology at the University of Regensburg. During this time, Dr. Hoffmann established a strong focus in neuroanesthesia and neurointensive care medicine.
In 2008, she began her postdoctoral fellowship at Harvard Medical School and began to work with Dr. Michael Moskowitz and Dr. Cenk Ayata in the Neurovascular Protection Laboratory at Massachusetts General Hospital. It was here that she began to devote her research to the development and exploration of new therapeutic options for acute brain injury. After returning to Germany, she completed residency in 2014 and also her PhD in neuroscience in 2014 at the Technical University of Munich. In spring of 2015, she joined the Division of Neuroanesthesiology at Duke University in the Department of Anesthesiology as a junior faculty member where she continues to conduct brain research.
Research
Since she started her research career in 1998, Dr. Hoffmann has been interested in studying cortical spreading depression (CSD), an electrophysiological phenomenon important to the pathophysiology of not only migraines but also brain injury states such as stroke, subarachnoid hemorrhage and traumatic brain injury. Injury depolarizations are important in the progression of tissue damage in ischemic stroke, subarachnoid hemorrhage and trauma. Much of the research on injury depolarizations has been focused on their origins, electrophysiological mechanisms and metabolic impact. Recent studies show that injury depolarizations cause vasoconstriction and diminish perfusion, which radically differs from the predominantly hyperemic response to spreading depression in otherwise-normal brain tissue. In addition to her clinical work with patients, Dr. Hoffmann was motivated to focus her bench research on the changes in neurovascular coupling and the occurrence of spreading ischemia as an important injury mechanism.
With the generous funds awarded by the DREAM Innovation Grant (DIG), Dr. Hoffmann will further explore how spreading depolarizations in the acutely injured brain evolve, supporting her work to characterize time patterns and options to diminish their occurrence thereby preventing the progression if an initial lesion. Argon as a potential therapeutic in stroke will be tested regarding its potency to afford neuroprotection, and she will assess its effect on the occurrence of spreading depolarizations and their accompanying cerebral blood flow characteristics.
Data from these initial studies will help to obtain extramural support for further studies, and in the future, develop much needed new therapies for patients with acute brain injury.