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Mild traumatic brain injury: Combined in silico and in vitro studies
Mild traumatic brain injury (TBI) is a significant public health concern worldwide and has attracted significant attention due to high-impact sport as well as improvised explosive devices used in military conflicts. The earliest sign of mild TBI is associated with cognitive, behavioral and physical/somatic changes, which are commonly invisible to existing medical techniques. Thus it is essential to target mechanisms of mild TBI and its associated damage measures for earlier diagnosis/treatment and enhanced protection strategies. ^ In this work, the mechanism of blast-induced mild TBI was inspected through integrated in silico and in vitro models. A three-dimensional (3D) human head model with anatomical details was reconstructed from high-resolution medical images, and positioned in three different directions with respect to the blast wave. The effects of head orientations as well as cerebral blood vessel network in brain mechanics were investigated. The dynamic responses of the brain were monitored by the maximum principal strain (MPS), shear strain (SS), and intracranial pressure (ICP). The developed numerical model was validated by the shock tube experiment using a surrogate head, i.e., water-filled polycarbonate shell. Results demonstrated that the ICP alternations in the brain was initially dominated by the direct blast wave propagation and the skull flexure took effect at a later time. It is worth noting that cerebral blood vessel network induced larger MPS and SS in the brain, which were influenced by vessel diameter and density. Moreover, the contour of the head and its orientation significantly altered the flow dynamics around the head, resulting in different spatial and temporal distributions of brain mechanics. Excessive mechanical stain sensed by brain cells, especially abundant cortical astrocytes, could be a potential index factor for the brain injury. ^ An in vitro injury model for primary cortical astrocytes was developed to identify the injury threshold. Rat cortical astrocytes cultured on silicone membrane were subjected to equibiaxial pulse stretch. The blast pressure profile on the membrane was monitored and the membrane deformations were captured through the high-speed imaging system. The simulated membrane strain, validated by experimental measures, was used to construct an exposure-response curve. It was observed that live cells declined sharply in the strain range from 18% to 35%, which was identified as the injury threshold of cortical astrocytes. ^ The obtained damage threshold of rat cortical astrocytes could be inferred about the level of brain injury in a rat. A 3D rat head model was constructed with an impactor mimicking the loading conditions of contact sports. Results revealed that impact depth and impactor shape were the two leading factors affecting brain dynamics. The influence of impactor diameter was region-specific and an increase in impactor diameter could substantially increase brain strains in the region which located directly beneath the impactor. The lateral impact could induce higher strains in the brain than the central impact. Results suggested that indentation depth instead of impact depth would be appropriate to characterize the influence of a softer impactor.^
Hua, Yi, "Mild traumatic brain injury: Combined in silico and in vitro studies" (2016). ETD collection for University of Nebraska - Lincoln. AAI10143296.