Preclinical evaluation of molecular imaging biomarkers for prediction of chronic traumatic encephalopathy (CTE).

• Applicant: Jens Bankstahl, Ph.D.
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Nuclear Medicine, Radiotherapy, Radiobiology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 443051306

Clinical evidence suggests repetitive mild traumatic brain injury (TBI) as a major cause of chronic traumatic encephalopathy (CTE) characterized by symptoms of dementia as well as neurodegeneration and a pathological deposition of tau protein. This proposal aims to provide a significant contribution towards a better understanding of consequences of repetitive mild TBI and CTE prediction. Only recently animal models mimicking CTE pathogenesis are available. In accordance with clinical observations, experimental data suggests crucial involvement of inflammatory processes in the pathogenesis of CTE. In this study, preclinical molecular imaging will be used to unveil the interaction of pathological processes (inflammation, changes in neuro-receptor systems, behavioral changes) induced by repetitive mild TBI. First, we aim to visualize the time course and regional distribution of neuroinflammation ([18F]GE180 (microglia activation) and [18F]fluorodeprenyl (astrocyte activation)), neuroreceptor expression ([18F]FPEB (mGluR5) and [18F]flumazenil (GABAA receptor)) and glucose metabolism ([18F]FDG PET) by translational positron emission tomography (PET) and autoradiography. As mild TBI occurs comparably often in sports activities and these sports are also performed by young individuals, pre-adult and adult rats will be compared within the planned experiments. The prognostic value of the imaging biomarkers will be analyzed in relation to the major outcome parameters, i.e. neurodegeneration, tau pathology and behavioral abnormalities. Furthermore and in addition to the imaging results of the neuroreceptor systems, potential pro-epileptogenic brain changes will be investigated by seizure threshold determination and behavioral hyper-excitability testing.

• DFG Programme: Research Grants