PROJECT: JTC2016: ICON-TBI

Neuroinflammation is mechanistically important in traumatic brain injury (TBI), may persist for years following ictus, could contribute to late cognitive decline, and might explain how TBI is an epigenetic driver for late neurodegeneration. Neuropathology and positron emission tomography suggest persistent microglial activation years after TBI, but such cross-sectional analyses cannot determine whether neuroinflammation drives ongoing neuronal loss. Recent interest has focused on the adaptive immune response after experimental neurotrauma, but data on its impact are conflicting. Microglial activation in experimental TBI results in variable phenotypes with pro-inflammatory or wound healing/anti-inflammatory roles, often classified as M1 or M2 responses. This is an oversimplification, but provides a conceptual framework to understand the repertoire of microglial response. Translation of these experimental data to clinical TBI is limited by the paucity of human data. Our international, multidisciplinary team will explore the neuroinflammatory response in complementary clinical studies in all severities and age ranges of TBI. These will be underpinned by concordant research in animal models, which not only address mechanistic questions, but also allow direct comparison with the unique human neuropathology data in the Glasgow TBI archive, and use genetic interventions and novel compounds (provided by our industrial partners) to study the modulation of neuroinflammation.