Biomarkers detected after TBI. This schematic figure demonstrates the possible cellular origin of the biomarkers that are associated with TBI pathology. TBI causes cellular injury to neuronal and nonneuronal cells. The trauma manifests in damaged BBB, ionic imbalances, energy depletion, and cell death. The cascade of events starts by an increase in extracellular glutamate and intra-axonal calcium levels. Increased calcium activates calpains, caspases, and phosphatases that trigger the cleavage of NFs and α-spectrin, which leads to the disruption of the cytoskeleton and cell death. Calcium also activates transcription factors that upregulate inflammatory mediators, such as TNF-α and IL-1β. In addition, mechanical injury causes synaptic dysfunction and accumulation and release of intracellular products, which impairs neurotransmission.
Kinetics of TBI biomarkers. Schematic representation shows the rise and decline of the TBI biomarkers for which representative kinetic data were available in serum or plasma. Separate long-term values (months to weeks) are included when possible.