Early Mechanistic Biomarkers for late Epilepsy and long-term Brain Injury Outcome Jens P. Dreier EBio2

Stroke and traumatic brain injuries (TBI) in humans are common causes of mortality and impose a poor quality of life on the affected individuals and their families. Life-saving treatments after brain injuries improved patients’ survival but long-term severe complications, such as motor and cognitive disabilities and epilepsy, still lack preventive treatments. Our studies indicate that specific structural and functional alterations involving neurons, glia and brain vessels underlie the progressive evolution of brain injuries and contribute to the late onset of epilepsy. The unmet need for early identification of these pathologic events in injured patients with clinically applicable approaches is the basis for the current project. Our ultimate goal is to improve current treatment interventions in brain-injured patients by discovering mechanism-driven biomarkers that will permit early preventive treatments for neurological complications. Through a combination approach based on improved and novel analyses of electrophysiological signals, brain magnetic resonance imaging (MRI) and selected blood molecules, we will search for common fingerprints of brain network dysfunctions reflecting disease progression using (1) our existing database of brain-injured patients with subarachnoid hemorrhage who underwent intensive neuromonitoring, serial MRI scans, blood collection, and were evaluated for epilepsy after 3 years, and (2) clinically relevant animal models of brain injury that are associated with late epilepsy development and allow neuromonitoring in a similar manner as in the ICU. We envision that monitoring of post-injury brain dynamics will allow us to develop biomarkers that identify patients at high-risk for developing a disease progressive course and epilepsy, thus permitting novel treatments to be applied timely following the concept of Personalized Medicine.