Massive Solubility Changes in Neuronal Proteins upon Simulated Traumatic Brain Injury Reveal the Role of Shockwaves in Irreversible Damage

This study investigated the immediate molecular consequences of traumatic brain injuries (TBIs) using a novel proteomics approach. Simulated TBIs, using a laboratory apparatus with a 5.1 kg dummy head impacting neuronal cells, generated ≤4000 g-force acceleration. A Proteome Integral Solubility Alteration (PISA) assay monitored protein solubility changes. Dynamic impacts reduced neuron viability and caused massive solubility changes in the proteome, affecting proteins in cell adhesion, collagen, laminin, stress response, immune response, complement, and coagulation cascades. The cellular effects were primarily due to shockwaves, not g-force acceleration. Soft materials reduced impact severity only until fully compressed. This research presents a proteome-based 'shock meter' for measuring irreversible shockwave-induced cell damage and provides resources for identifying TBI protein biomarkers and potential drug targets.

Amir Ata Saei, Hassan Gharibi, Hezhe Lyu, Brady Nilsson, Maryam Jafari, Hans Von Holst, Roman A Zubarev