Traumatic Brain Injury Biomarkers, Simulations and Kinetics

Abstract

This paper reviews the predictive capabilities of blood-based biomarkers to quantify traumatic brain injury (TBI). Biomarkers for concussive conditions also known as mild, to moderate and severe TBI identified along with post-traumatic stress disorder (PTSD) and chronic traumatic encephalopathy (CTE) that occur due to repeated blows to the head during one’s lifetime. Since the pathways of these biomarkers into the blood are not fully understood whether there is disruption in the blood–brain barrier (BBB) and the time it takes after injury for the expression of the biomarkers to be able to predict the injury effectively, there is a need to understand the protein biomarker structure and other physical properties. The injury events in terms of brain and mechanics are a result of external force with or without the shrapnel, in the wake of a wave result in local tissue damage. Thus, these mechanisms express specific biomarkers kinetics of which reaches half-life within a few hours after injury to few days. Therefore, there is a need to determine the concentration levels that follow injury. Even though current diagnostics linking biomarkers with TBI severity are not fully developed, there is a need to quantify protein structures and their viability after injury. This research was conducted to fully understand the structures of 12 biomarkers by performing molecular dynamics simulations involving atomic movement and energies of forming hydrogen bonds. Molecular dynamics software, NAMD and VMD were used to determine and compare the approximate thermodynamic stabilities of the biomarkers and their bonding energies. Five biomarkers used clinically were S100B, GFAP, UCHL1, NF-L and tau, the kinetics obtained from literature show that the concentration values abruptly change with time after injury. For a given protein length, associated number of hydrogen bonds and bond energy describe a lower bound region where proteins self-dissolve and do not have long enough half-life to be detected in the fluids. However, above this lower bound, involving higher number of bonds and energy, we hypothesize that biomarkers will be viable to disrupt the BBB and stay longer to be modeled for kinetics for diagnosis and therefore may help in the discoveries of new biomarkers.