Lawrence E. Thibault

Biomechanics of Acute Subdural Hematoma

Acute subdural hematoma (ASDH) due to ruptured bridging veins occurs under acceleration conditions associated with rates of acceleration onset. That this is due to the strain-rate sensitivity of these veins was confirmed in an experimental model of ASDH. The results of this model were consistent with the clinical causes of ASDH, where 72% are due to high-strain falls and assaults and 24% are due to lower strain-rate vehicular injuries. A mathematical model embodying the known mechanical properties of subdural veins was used to develop tolerance criteria for the occurrence of ASDH. This tolerance curve was consistent with the clinical and experimental data but differed from tolerances previously proposed for head injury.

A proposed tolerance criterion for diffuse axonal injury in man.

The head injury criterion (HIC) is currently the government-accepted head injury indicator. The HIC is not injury-specific, does not relate to injury severity, nor does it take into account variations in the brain mass or load direction. This report focuses on one type of inertial brain injury, diffuse axonal injury (DAI), and utilizes animal studies, physical model experiments, and analytical model simulations to determine the kinematics of DAI in the subhuman primate and to scale these results to man. A human injury tolerance for moderate to severe DAI, which includes the influences of rotational loads and brain mass, is proposed.

Physical model simulations of brain injury in the primate

Diffuse brain injuries resulting from non-impact rotational acceleration are investigated with the aid of physical models of the skull-brain structure. These models provide a unique insight into the relationship between the kinematics of head motion and the associated deformation of the surrogate brain material. Human and baboon skulls filled with optically transparent surrogate brain tissue are subjected to lateral rotations like those shown to produce diffuse injury to the deep white matter in the brain of the baboon. High-speed cinematography captures the deformations of the grids embedded within the surrogate brain tissue during the applied load. The overall deformation pattern is compared to the pathological portrait of diffuse brain injury as determined from animal studies and autopsy reports. Shear strain and pathology spatial distributions mirror each other. Load levels and resulting surrogate brain tissue deformations are related from one species to the other. Increased primate brain mass magnified the strain amplified without significantly altering the spatial distribution. An empirically-derived value for a critical shear strain associated with the onset of severe diffuse axonal injury in primates is determined, assuming constitutive similarity between baboon and human brain tissue. The primate skull physical model data and the critical shear strain associated with the threshold for severe diffuse axonal injury were used to scale data obtained from previous studies to man, and thus derive a diffuse axonal injury tolerance for rotational acceleration for humans.

The mechanical properties of the human cervical spinal cord in vitro

The response of spinal cord tissue to mechanical loadings is not well understood. In this study, isolated fresh cervical spinal cord samples were obtained from cadavers at autopsy and tested in uniaxial tension at moderate strain rates. Stress relaxation experiments were performed with an applied strain rate and peak strain in the physiological range, similar to those seen in the spinal cord during voluntary motion. The spinal cord samples exhibited a nonlinear stress-strain response with increasing strain increasing the tangent modulus. In addition, significant relaxation was observed over 1 min. A quasilinear viscoelastic model was developed to describe the behavior of the spinal cord tissue and was found to describe the material behavior adequately. The data also were fitted to both hyperelastic and viscoelastic fluid models for comparison with other data in the literature.

Diffuse Axonal Injury: An Important Form of Traumatic Brain Damage

Diffuse axonal injury (DAI) is a frequent form of traumatic brain injury in which a clinical spectrum of in creasing injury severity is paralleled by progressively increasing amounts of axonal damage in the brain. When less severe, DAI is associated with concussive syndromes; when most severe, it causes prolonged traumatic coma that is not related to mass lesions, increased intracranial pressure, or ischemia. Pathological investigations of DAI demonstrate widespread but heterogeneous microscopic damage to axons throughout the white matter of the cerebral and cerebellar hemispheres and brainstem. There is a propensity for injury to occur in the central third of the brain, and the corpus callosum and brain stem are especially prone to injury. In these locations, traumatic axonal damage can occur in several degrees of severity, ranging from transient disturbances of ionic homeostasis to swelling, impairment of axoplasmic transport with secondary (delayed) axotomy and primary axotomy (tearing). A more detailed understanding of the processes involved in axonal damage is crucial to the development of effective treatment for the clinical syndromes of DAI. NEUROSCIENTIST 4:202-215, 1998

An Analytical Model of Traumatic Diffuse Brain Injury

Diffuse axonal injury (DAI) with prolonged coma has been produced in the primate using an impulsive, rotational acceleration of the head without impact. This pathophysiological entity has been studied subsequently from a biomechanics perspective using physical models of the skull-brain structure. Subjected to identical loading conditions as the primate, these physical models permit one to measure the deformation within the surrogate brain tissue as a function of the forces applied to the head. An analytical model designed to approximate these experiments has been developed in order to facilitate an analysis of the parameters influencing brain deformation. These three models together are directed toward the development of injury tolerance criteria based upon the shear strain magnitude experienced by the deep white matter of the brain. The analytical model geometry consists of a rigid, right-circular cylindrical shell filled with a Kelvin-Voigt viscoelastic material. Allowing no slip on the boundary, the shell is subjected to a sudden, distributed, axisymmetric, rotational load. A Fourier series representation of the load allows unrestricted load-time histories. The exact solution for the relative angular displacement (V) and the infinitesimal shear strain (epsilon) at any radial location in the viscoelastic material with respect to the shell was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

In Vitro Cell Shearing Device to Investigate the Dynamic Response of Cells in a Controlled Hydrodynamic Environment

AbstractMechanical stresses and strains play important roles in the normal growth and development of biological tissues, yet the cellular mechanisms of mechanotransduction have not been identified. A variety of in vitro systems for applying mechanical loads to cell populations have been developed to gain insight into these mechanisms. However, limitations in the ability to control precisely relevant aspects of the mechanical stimuli have obscured the physical relationships between mechanical loading and the biochemical signals that mediate the cellular response. We present a novel in vitro cell shearing device based on the principles of a cone and plate viscometer that utilizes microstepper motor technology to control independently the dynamic and steady components of a hydrodynamic shear-stress environment. Physical measurements of the cone velocity demonstrated faithful reproduction of user-defined input wave forms. Computational modeling of the fluid environment for the unsteady startup confirmed small inertial contributions and negligible secondary flows. Finally, we present experimental results demonstrating the onset rate dependence of functional and structural responses of endothelial cell cultures to dynamically applied shear stress. The controlled cell shearing device is a novel tool for elucidating mechanisms by which mechanical forces give rise to the biological signals that modulate cellular morphology and metabolism.

Strain measurements in cultured vascular smooth muscle cells subjected to mechanical deformation

Early work in the field of biomechanics employed rigorous application of the principles of mechanics to the study of the macroscopic structural response of tissues to applied loads. Interest in the functional response of tissues to mechanical stimulation has lead researchers to study the biochemical responses of cells to mechanical loading. Characterization of the experimental system (i.e., specimen geometry and boundary conditions) is no less important on the microscopic scale of the cell than it is for macroscopic tissue testing. We outline a method for appropriate characterization of cell deformation in a cell culture model; describe a system for applying a uniform, isotropic strain field to cells in culture; and demonstrate a dependence of cell deformation on morphology and distribution of adhesion sites. Cultured vascular smooth-muscle cells were mechanically deformed by applying an isotropic strain to the compliant substrate to which they were adhered. The state of strain in the cells was determined by measurement of the displacements of fluorescent microspheres attached to the cell surface. The magnitude and orientation of principal strains were found to vary spatially and temporally and to depend on cell morphology. These results show that cell strain can be highly variable and emphasize the need to characterize both the loading conditions and the actual cellular deformation in this type of experimental model.

Anin vitro traumatic injury model to examine the response of neurons to a hydrodynamically-induced deformation

A novelin vitro system was developed to examine the effects of traumatic mechanical loading on individual cells. The cell shearing injury device (CSID) is a parallel disk viscometer that applies fluid shear stress with variable onset rate. The CSID was used in conjunction with microscopy and biochemical techniques to obtain a quantitative expression of the deformation and functional response of neurons to injury. Analytical and numerical approximations of the shear stress at the bottom disk were compared to determine the contribution of secondary flows. A significant portion of the shear stress was directed in ther-direction during start-up, and therefore the full Navier-Stokes equation was necessary to accurately describe the transient shear stress. When shear stress was applied at a high rate (800 dyne cm−2 sec−1) to cultured neurons, a range of cell membrane strains (0.01 to 0.53) was obtained, suggesting inhomogeneity in cellular response. Functionally, cytosolic calcium and extracellular lactate dehydrogenase levels increased in response to high strain rate (>1 sec−1) loading, compared with quasistatic (<1 sec−1) loading. In addition, a subpopulation of the culture subjected to rapid deformation subsequently died. These strain rates are relevant to those shown to occur in traumatic injury, and as such, the CSID is an appropriate model for studying the biomechanics and pathophysiology of neuronal injury.

Dynamic mechanical deformation of neurons triggers an acute calcium response and cell injury involving the N-methyl-D-aspartate glutamate receptor

A biomechanical in vitro model of traumatic brain injury was used to examine cellular response to physical insults and the underlying mechanisms that lead to cell dysfunction. A cell shearing injury device was used to deform human NTera‐2 neurons at high loading rates during the investigation of mechanisms of cytosolic free calcium increases, which may be detrimental to a cell. Cytosolic free calcium rose immediately to almost three times baseline and was associated with lactate dehydrogenase release at 24 hr, indicating significant cell injury. Low loading rates did not elicit these responses. A major portion of the calcium increase and subsequent cell injury was dependent on the presence of extracellular free calcium. Blocking the N‐methyl‐D‐aspartate glutamate receptor complex with dizocilipine maleate attenuated calcium increases by 45% in injured neurons and blocked a significant part (50%) of the lactate dehydrogenase release. In addition, pretreatment with nifedipine or riluzole also significantly reduced cytosolic free calcium but did not affect cell injury, whereas tetrodotoxin had no affect on either outcome parameter. These results suggest that the increased membrane permeability and immediate calcium influx associated with this model of mechanical injury trigger several cellular pathways, including N‐methyl‐D‐aspartate receptor‐mediated cell damage. J. Neurosci. Res. 52:220–229, 1998. © 1998 Wiley‐Liss, Inc.