Subcellular and macrostructural immediate responders to airblast traumatic brain injury

Traumatic Brain Injury (TBI) affects millions of people each year, causing loss of workforce, a significant burden on the healthcare system. Research into the biological effects of TBI has focused on cellular and tissue responses in the order of hours to days after exposure. Unfortunately, treatments that address these secondary processes after TBI have not been effective. Addressing earlier events and identifying first responders is necessary to prevent or limit irreversible damage. Here, we analyze molecular and cellular changes that occur during and immediately after injury in the somatosensory cortex of mice after an airblast TBI using various techniques. Early changes recorded within 5 min of TBI injury show persistent calcium activation, followed by unique phosphorylation patterns activating specific protein binding and calcium-activated pathways. Imaging mass lipidomics and Raman microspectroscopy identified conformational changes of lipid membranes, pointing towards membrane damage as the first response to mechanical pressure. Real-time monitoring of blood vessels shows rapid constriction followed by reduced blood flow within minutes of injury. The present study uncovers the early sequence of events in TBI: ionic calcium imbalance occurs within seconds, activating subcellular phosphorylation patterns, which in turn trigger downstream pathways and a parallel destabilization of membrane phospholipids.