The influence of the tertiary bronchi on dynamic lung deformation.

Finite element models of thoracic injury often treat the lung as a bulk homogeneous and isotropic material, which reduces the computational costs associated with such investigations. Ignoring the heterogeneous structure of the lung may be computationally expedient, but this simplification may inadvertently fail to capture the true lung strain dynamics. In the present work, a series of direct impact experiments were performed on porcine lungs, inflated to a relevant expiratory pressure, and monitored using high-speed X-ray imaging. The lungs were instrumented with radiopaque markers within the parenchyma and tertiary bronchi to monitor the resulting deformation mechanics. The deformation mechanics demonstrate a high degree of strain localization related to the structural heterogeneity of the lung. The relative motion of the tertiary bronchi was measured during the impact event, and used to estimate the parenchyma tissue strains in the inter-bronchial regions. These were shown to exceed the trans-lobe strains by a factor 3 to 5 times higher in their tensile, compressive, and shear strain responses. Our results demonstrate that the lung parenchyma and bronchial tissues form a heterogeneous structure with a substantial stiffness differential that cannot be appropriately modelled as a homogeneous and isotropic monolithic mass without loss of accuracy and predictive relevance.

Relating strain fields with microtubule changes in porcine cortical sulci following drop impact.

The biomechanical response of brain tissue to strain and the immediate neural outcomes are of fundamental importance in understanding mild traumatic brain injury (mTBI). The sensitivity of neural tissue to dynamic strain events and the resulting strain-induced changes are considered to be a primary factor in injury. Rodent models have been used extensively to investigate impact-induced injury. However, the lissencephalic structure is inconsistent with the human brain, which is gyrencephalic (convoluted structure), and differs considerably in strain field localization effects. Porcine brains have a similar structure to the human brain, containing a similar ratio of white-grey matter and gyrification in the cortex. In this study, coronal brain slabs were extracted from female pig brains within 2hrs of sacrifice. Slabs were implanted with neutral density radiopaque markers, sealed inside an elastomeric encasement, and dropped from 0.9 m onto a steel anvil. Particle tracking revealed elevated tensile strains in the sulcus. One hour after impact, decreased microtubule associated protein 2 (MAP2) was found exclusively within the sulcus with no increase in cell death. These results suggest that elevated tensile strain in the sulcus may result in compromised cytoskeleton, possibly indicating a vulnerability to pathological outcomes under the right circumstances. The results demonstrated that the observed changes were unrelated to shear strain loading of the tissues but were more sensitive to tensile load.

Impact-Induced Cortical Strain Concentrations at the Sulcal Base and Its Implications for Mild Traumatic Brain Injury.

This study investigated impact-induced strain fields within brain tissue surrogates having different cortical gyrification. Two elastomeric surrogates, one representative of a lissencephalic brain and the other of a gyrencephalic brain, were drop impacted in unison at four different heights and in two different orientations. Each surrogate contained a radiopaque speckle pattern that was used to calculate strain fields. Two different approaches, digital image correlation (DIC) and a particle tracking method, enabled comparisons of full-field and localized strain responses. The DIC results demonstrated increased localized deviations from the mean strain field in the surrogate with a gyrified cortex. Particle tracking algorithms, defining four-node quadrilateral elements, were used to investigate the differences in the strain response of three regions: the base of a sulcus, the adjacent gyrus, and the internal capsule of the surrogates. The results demonstrated that the strains in the cortex were concentrated at the sulcal base. This mechanical mechanism of increased strain is consistent with neurodegenerative markers observed in postmortem analyses, suggesting a potential mechanism of local damage due to strain amplification at the sulcal bases in gyrencephalic brains. This strain amplification mechanism may be responsible for cumulative neurodegeneration from repeated subconcussive impacts. The observed results suggest that lissencephalic animal models, such as rodents, would not have the same modes of injury present in a gyrencephalic brain, such as that of a human. As such, a shift toward representative mild traumatic brain injury animal models having gyrencephalic cortical structures should be strongly considered.

Effects on Neurons and Hippocampal Slices by Single and Multiple Primary Blast Pressure Waves From Detonating Spherical Cyclotrimethylenetrinitramine (RDX) Explosive Charges.

Threshold shock-impulse levels required to induce cellular injury and cumulative effects upon single and/or multiple exposures are not well characterized. Currently, there are few in vitro experimental models with blast pressure waves generated by using real explosives in the laboratory for investigating the effects of primary blast-induced traumatic brain injury. An in vitro indoor experimental platform is developed using real military explosive charges to accurately represent battlefield blast exposure and to probe the effects of primary explosive blast on dissociated neurons and tissue slices. Preliminary results indicate that physical insults altered membrane permeability, impacted cellular viability, created axonal beadings, and led to synaptic protein loss in hippocampal slice cultures. Injuries from blast under the conditions that were examined did not appear to cause immediate or sustained damage to the cells. Three consecutive primary blasts failed to disrupt the overall cellular integrity in the hippocampal slice cultures and produced a unique type of pathology comprised with distinct reduction in synaptic proteins before cellular deterioration set in. These observed changes might add to the challenges in regard to enhancing our understanding of the complex biochemical and molecular mechanisms caused by primary blast-induced injury.

Effects of repetitive low-pressure explosive blast on primary neurons and mixed cultures.

Repetitive mild traumatic brain injury represents a considerable health concern, particularly for athletes and military personnel. For blast-induced brain injury, threshold shock-impulse levels required to induce such injuries and cumulative effects with single and/or multiple exposures are not well characterized. Currently, there is no established in vitro experimental model with blast pressure waves generated by live explosives. This study presents results of primary neurons and mixed cultures subjected to our unique in vitro indoor experimental platform that uses real military explosive charges to probe the effects of primary explosive blast at the cellular level. The effects of the blast on membrane permeability, generation of reactive oxygen species (ROS), uptake of sodium ions, intracellular calcium, and release of glutamate were probed 2 and 24 hr postblast. Significant changes in membrane permeability and sodium uptake among the sham, single-blast-injured, and triple-blast-injured samples were observed. A significant increase in ROS and glutamate release was observed for the triple-blast-injured samples compared with the sham. Changes in intracellular calcium were not significant. These results suggest that blast exposure disrupts the integrity of the plasma membrane, leading to the upset of ion homeostasis, formation of ROS, and glutamate release. Published 2016. †This article is a U.S. Government work and is in the public domain in the USA.

The effect of explosive blast loading on human neuroblastoma cells.

Diagnosis of mild to moderate traumatic brain injury is challenging because brain tissue damage progresses slowly and is not readily detectable by conventional imaging techniques. We have developed a novel in vitro model to study primary blast loading on dissociated neurons using nitroamine explosives such as those used on the battlefield. Human neuroblastoma cells were exposed to single and triple 50-psi explosive blasts and single 100-psi blasts. Changes in membrane permeability and oxidative stress showed a significant increase for the single and triple 100-psi blast conditions compared with single 50-psi blast and controls.

Investigating the effects of membrane deformability on artificial capsule adhesion to the functionalized surface.

Understanding, manipulating and controlling cellular adhesion processes can be critical in developing biomedical technologies. Adhesive mechanisms can be used to the target, pattern and separate cells such as leukocytes from whole blood for biomedical applications. The deformability response of the cell directly affects the rolling and adhesion behavior under viscous linear shear flow conditions. To that end, the primary objective of the present study was to investigate numerically the influence of capsule membrane's nonlinear material behavior (i.e. elastic-plastic to strain hardening) on the rolling and adhesion behavior of representative artificial capsules. Specifically, spherical capsules with radius of [Formula: see text] were represented using an elastic membrane governed by a Mooney-Rivlin strain energy functions. The surfaces of the capsules were coated with P-selectin glycoprotein-ligand-1 to initiate binding interaction with P-selectin-coated planar surface with density of [Formula: see text] under linear shear flow varying from 100 to [Formula: see text]. The numerical model is based on the Immersed Boundary Method for rolling of deformable capsule in shear flow coupled with Monte Carlo simulation for receptor/ligand interaction modeled using Bell model. The results reveal that the mechanical properties of the capsule play an important role in the rolling behavior and the binding kinetics between the capsule contact surface and the substrate. The rolling behavior of the strain hardening capsules is relatively smoother and slower compared to the elastic-plastic capsules. The strain hardening capsules exhibits higher contact area at any given shear rate compared to elastic-plastic capsules. The increase in contact area leads to decrease in rolling velocity. The capsule contact surface is not in complete contact with the substrate because of thin lubrication film that is trapped between the capsule and substrate. This creates a concave shape on the bottom surface of the capsule that is referred to as a dimple. In addition, the present study demonstrates that the average total bond force from the capsules lifetime increases by 37 % for the strain hardening capsules compared to elastic-plastic capsules at shear rate of [Formula: see text]. Finally, the model demonstrates the effect of finite membrane deformation on the coupling between hydrodynamic and receptor/ligand interaction.

In vitro studies of primary explosive blast loading on neurons.

In a military setting, traumatic brain injury (TBI) is frequently caused by blast waves that can trigger a series of neuronal biochemical changes. Although many animal models have been used to study the effects of primary blast waves, elucidating the mechanisms of damage in a whole-animal model is extremely complex. In vitro models of primary blast, which allow for the deconvolution of mechanisms, are relatively scarce. It is largely unknown how structural damage at the cellular level impacts the functional activity at variable time scales after the TBI event. A novel in vitro system was developed to probe the effects of explosive blast (ranging from ∼25 to 40 psi) on dissociated neurons. PC12 neurons were cultured on laminin-coated substrates, submerged underwater, and subjected to single and multiple blasts in a controlled environment. Changes in cell membrane permeability, viability, and cell morphology were evaluated. Significant increases in axonal beading were observed in the injured cells. In addition, although cell death was minimal after a single insult, cell viability decreased significantly following repeated blast exposure.