Multiscale Structure of Brain and Challenges in Traumatic Brain Injury Risk Prediction

This study aims to provide an overview of the recent developments in understanding multiscale traumatic brain injury (TBI) mechanisms from a multidisciplinary perspective. TBI is a major cause of death and disability in the United States, affecting people of all ages, genders, and races. On average, in every 5 s, someone in the U.S. experiences TBI-related injuries. According to the CDC, in 2019, there were more than 200,000 TBI-related hospitalizations in the USA. TBI is the most common traumatic injury in the U.S. military. As such, researchers from different fields attempt to investigate TBI risks and propose injury criteria. Yet, a unified TBI risk criterion is not available. This is primarily because the human brain has an overly complex and multiscale anatomy. From a length scale standpoint, the existing brain injury thresholds can be divided over three main scales and criteria: macroscale, tissue level, and cellular level. Macroscale criteria use quantifiable parameters such as acceleration and pressure that are typically taken on or near the head surface. Tissue level criteria are based on internal stress or strain-based injury analysis. Cellular-level injury analyses are based on molecular-level computations and cell culture, which is an emerging sector in brain injury threshold detection. However, there is a significant gap in the literature on connecting the parameters of the three scales and establishing a comprehensive injury criterion. We reviewed a combination of recent multidisciplinary evidence-informed literature and tried to connect the gaps by combining the three scales of TBI. Finally, we summarized the future challenges researchers may face and how we can approach and make progress in detecting TBI accurately.