Abstract
Traumatic brain injury (TBI) is an extremely complex disease and current systems classifying TBI as mild, moderate, and severe often fail to capture this complexity. Neuroimaging cannot resolve the cellular and molecular changes due to lack of resolution, and post-mortem tissue examination may not adequately represent acute disease. Therefore, we examined the cellular and molecular sequelae of TBI in fresh brain samples and related these to clinical outcomes. Brain biopsies, obtained shortly after injury from 25 living adult patients suffering severe TBI, underwent immunohistochemical analysis. There were no adverse events. Immunostaining revealed various qualitative cellular and biomolecular changes relating to neuronal injury, dendritic injury, neurovascular injury, and neuroinflammation, which we classified into 4 subgroups for each injury type using the newly devised Yip, Hasan and Uff (YHU) grading system. Based on the Glasgow Outcome Scale-Extended, a total YHU grade of ≤8 or ≥11 had a favourable and unfavourable outcome, respectively. Biomolecular changes observed in fresh brain samples enabled classification of this heterogeneous patient population into various injury severity categories based on the cellular and molecular pathophysiology according to the YHU grading system, which correlated with outcome. This is the first study investigating the acute biomolecular response to TBI.