Altered Tau Kinase Activity in rTg4510 Mice after a Single Interfaced CHIMERA Traumatic Brain Injury.

Traumatic brain injury (TBI) is an established risk factor for neurodegenerative diseases. In this study, we used the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) to investigate the effects of a single high-energy TBI in rTg4510 mice, a mouse model of tauopathy. Fifteen male rTg4510 mice (4 mo) were impacted at 4.0 J using interfaced CHIMERA and were compared to sham controls. Immediately after injury, the TBI mice showed significant mortality (7/15; 47%) and a prolonged duration of loss of the righting reflex. At 2 mo post-injury, surviving mice displayed significant microgliosis (Iba1) and axonal injury (Neurosilver). Western blotting indicated a reduced p-GSK-3ß (S9):GSK-3ß ratio in TBI mice, suggesting chronic activation of tau kinase. Although longitudinal analysis of plasma total tau suggested that TBI accelerates the appearance of tau in the circulation, there were no significant differences in brain total or p-tau levels, nor did we observe evidence of enhanced neurodegeneration in TBI mice compared to sham mice. In summary, we showed that a single high-energy head impact induces chronic white matter injury and altered GSK-3ß activity without an apparent change in post-injury tauopathy in rTg4510 mice.

Geometric and Inertial Properties of the Pig Head and Brain in an Anatomical Coordinate System.

Porcine models in injury biomechanics research often involve measuring head or brain kinematics. Translation of data from porcine models to other biomechanical models requires geometric and inertial properties of the pig head and brain, and a translationally relevant anatomical coordinate system (ACS). In this study, the head and brain mass, center of mass (CoM), and mass moments of inertia (MoI) were characterized, and an ACS was proposed for the pre-adolescent domestic pig. Density-calibrated computed tomography scans were obtained for the heads of eleven Large White × Landrace pigs (18-48 kg) and were segmented. An ACS with a porcine-equivalent Frankfort plane was defined using externally palpable landmarks (right/left frontal process of the zygomatic bone and zygomatic process of the frontal bone). The head and brain constituted 7.80 ± 0.79% and 0.33 ± 0.08% of the body mass, respectively. The head and brain CoMs were primarily ventral and caudal to the ACS origin, respectively. The mean head and brain principal MoI (in the ACS with origin at respective CoM) ranged from 61.7 to 109.7 kg cm2, and 0.2 to 0.6 kg cm2, respectively. These data may aid the comparison of head and brain kinematics/kinetics data and the translation between porcine and human injury models.

Evaluating femoral augmentation to prevent geriatric hip fracture: A scoping review of experimental methods.

Various femoral augmentation designs have been investigated over the past decade for the prevention of geriatric hip fracture. The experimental methods used to evaluate the efficacy of these augmentations have not been critically evaluated or compared in terms of biofidelity, robustness, or ease of application. Such parameters have significant relevance in characterizing future clinical success. In this study we aimed to use a scoping review to summarize the experimental studies that evaluate femoral augmentation approaches, and critically evaluate commonly applied protocols and identify areas for concordance with the clinical situation. We conducted a literature search targeting studies that used experimental test methods to evaluate femoral augmentation to prevent geriatric fragility fracture. A total of 25 studies met the eligibility criteria. The most commonly investigated augmentation to date is the injection of bone cement or another material that cured in situ, and a popular subsequent method for biomechanical evaluation was to load the augmented proximal femur until fracture in a sideways fall configuration. We noted limitations in the clinical relevance of sideways fall scenarios being modeled and large variance in the concordance of many of the studies identified. Our review brings about recommendations for enhancing the fidelity of experimental methods modeling clinical sideways falls, which include an improved representation of soft tissue effects, using outcome metrics beyond load-to-failure, and applying loads inertially. Effective augmentations are encouraging for their potential to reduce the burden of hip fracture; however, the likelihood of this success is only as strong as the methods used in their evaluation.

The efficacy of femoral augmentation for hip fracture prevention using ceramic-based cements: A preliminary experimentally-driven finite element investigation.

Femoral fractures due to sideways falls continue to be a major cause of concern for the elderly. Existing approaches for the prevention of these injuries have limited efficacy. Prophylactic femoral augmentation systems, particularly those involving the injection of ceramic-based bone cements, are gaining more attention as a potential alternative preventative approach. We evaluated the mechanical effectiveness of three variations of a bone cement injection pattern (basic ellipsoid, hollow ellipsoid, small ellipsoid) utilizing finite element simulations of sideways fall impacts. The basic augmentation pattern was tested with both high- and low-strength ceramic-based cements. The cement patterns were added to the finite element models (FEMs) of five cadaveric femurs, which were then subject to simulated sideways falls at seven impact velocities ranging from 1.0 m/s to 4.0 m/s. Peak impact forces and peak acetabular forces were examined, and failure was evaluated using a strain-based criterion. We found that the basic HA ellipsoid provided the highest increases in both the force at the acetabulum of the impacted femur ("acetabular force", 55.0% ± 22.0%) and at the force plate ("impact force", 37.4% ± 15.8%). Changing the cement to a weaker material, brushite, resulted in reduced strengthening of the femur (45.2% ± 19.4% acetabular and 30.4% ± 13.0% impact). Using a hollow version of the ellipsoid appeared to have no effect on the fracture outcome and only a minor effect on the other metrics (54.1% ± 22.3% acetabular force increase and 35.3% ± 16.0% impact force increase). However, when the outer two layers of the ellipsoid were removed (small ellipsoid), the force increases that were achieved were only 9.8% ± 5.5% acetabular force and 8.2% ± 4.1% impact force. These results demonstrate the importance of supporting the femoral neck cortex to prevent femoral fractures in a sideways fall, and provide plausible options for prophylactic femoral augmentation. As this is a preliminary study, the surgical technique, the possible effects of trabecular bone damage during the augmentation process, and the effect on the blood supply to the femoral head must be assessed further.

Incorporating neck biomechanics in helmet testing: Evaluation of commercially available WaveCel helmets.

BACKGROUND: Cycling helmets often incorporate elements aimed to dissipate rotational energies, which is widely acknowledged to play a key role in concussion mechanics. In this study, we investigated the mechanics of an oblique helmet test protocol that induced helmet rotation while using it to evaluate the effectiveness of three helmet models: two standard expanded polystyrene helmets and a commercially-available helmet equipped with a liner designed to mitigate linear and rotational energies. METHODS: Helmets equipped with WaveCel were tested against two expanded polystyrene helmet models through guided drops using a Hybrid III (HIII) head-and-neck surrogate. The three helmet models were tested across four impact conditions (n = 5) of different speeds and impact surface angles. FINDINGS: Across all tests, a similar sequence of head motion was observed - first a flexion phase followed by an extension phase. The extension phase lacked evidence of biofidelity and was likely attributable to the energy stored in the neckform during the flexion phase; it was therefore neglected from analysis. Results showed WaveCel reduced the probability of AIS2 head injury across all tests (3 to 27% reductions in 4.8 m/s impacts; 36 to 37% reductions in 6.2 m/s impacts). INTERPRETATION: The two-phased response of the HIII suggests that boundary condition selection can influence results and should thus be reported in studies using similar methods. While this protocol involved both axial and tangential impact components and were thus representative of real-world collisions, the efficacy of WaveCel should be further investigated through additional laboratory studies and tracking real-world cycling injury statistics.

Prophylactic augmentation implants in the proximal femur for hip fracture prevention: An in silico investigation of simulated sideways fall impacts.

Femoral fractures from sideways falls in the elderly are associated with significant rates of morbidity and mortality. Approaches to prevent these catastrophic injuries include pharmacological treatments, which have limited efficacy. Prophylactic femoral augmentation systems are a promising alternative that are gaining prominence by addressing the most debilitating osteoporosis-related fracture. We have developed finite element models (FEMs) of a novel experimental sideways fall simulator for cadavers. By virtue of the range of specimens and injury outcomes, these FEMs are well-suited to the evaluation of such implants. The purpose of this study was to use the FEMs to evaluate the mechanical effectiveness of three different prophylactic femoral augmentation systems. Models of the Y-Strut® (Hyprevention®, Pessac, France), Gamma Nail® (Stryker, Kalamazoo, USA), and a simple lag screw femoral fracture implant systems were placed into FEMs of five cadaveric pelvis-femur constructs embedded in a soft tissue surrogate, which were then subject to simulated sideways falls at seven impact velocities. Femur-only FEMs were also evaluated. Peak impact forces and peak acetabular forces were examined, and failure was evaluated using a strain-based criterion. We found that the femoral augmentation systems increased the peak forces prior to fracture, but were unable to prevent fracture for severe impacts. The Gamma Nail® system consistently produced the largest strength increases relative to the unaugmented femur for all five specimens in both the pendulum-drop FEMs and the femur-only simulations. In some cases, the same implant appeared to cause fractures in the acetabulum. The femur-only FEMs showed larger force increases than the pendulum-drop simulations, which suggests that the results of the femur-only simulations may not represent sideways falls as accurately as the soft tissue-embedded pendulum-drop simulations. The results from this study demonstrate the ability to simulate a high energy phenomenon and the effect of implants in an in silico environment. The results also suggest that implants could increase the force applied to the proximal femur during impact. Fracture outcomes from the tested implants can be used to inform the design of future devices, which reaffirms the value of modelling with biofidelic considerations in the implant design process. To the authors' knowledge, this is the first paper to use more complex biofidelic FEMs to assess prophylactic femoral augmentation methods.

Methodology to measure seat belt fit in relation to skeletal geometry using an upright open MRI.

OBJECTIVE: Poor seat belt fit can result in submarining behavior and injuries to the lower extremity and abdomen. While previous studies have explored seat belt fit relative to skeletal landmarks using palpation, medical imaging remains the gold standard for visualizing and locating skeletal landmarks and soft tissues. The goal of this study was to create a method to image automotive postures and seat belt fit from the pelvis to the clavicle using an Upright Open MRI. METHODS: The posture and belt fit of 10 volunteers (5M, 5F) were measured in an Acura TLX in each subject's preferred driving posture and a standard reclined posture, and then reproduced in a custom non-ferromagnetic seat replica in the MR scanner with an MRI-visible seat belt. The MRI sequence and coil placement were designed to yield clear visualization of bone, soft tissue borders, and the seat belt markers in separate scans of the pelvis, lumbar, thoracolumbar, and thoracic regions. A process was developed to precisely register the scans, and methods for digitizing spinal and pelvic landmarks were established to quantify belt fit. CONCLUSIONS: This method creates opportunities to study variation in seat belt fit in different automotive postures, for occupants of different sexes, ages, BMIs, anthropometries, and for pregnant occupants.

Anteroposterior shear stiffness of the upper thoracic spine at quasi-static and dynamic loading rates-An in vitro biomechanical study.

To evaluate the biomechanical properties of the upper thoracic spine in anterior-posterior shear loading at various displacement rates. These data broaden our understanding of thoracic spine biomechanics and inform efforts to model the spine and spinal cord injuries. Seven T1-T2 thoracic functional spinal units were loaded non-destructively by a pure shear force up to 200 N, starting from a neutral posture. Tests were run in both posterior and anterior directions, at displacement rates of 1, 10, and 100 mm/s. The three-dimensional motion of the specimen was recorded at 1000 Hz. Individual and averaged load-displacement curves were generated and specimen stiffnesses were calculated. Due to a nonlinear response of the specimens, stiffness was defined separately for both the lower half and the upper half of the specimen range of motion. Specimens were significantly stiffer in the anterior direction than in the posterior direction, across all rates. At low displacements, the anterior stiffness averaged 230 N/mm, 76% higher than the low displacement posterior stiffness of 131 N/mm. At high displacements, anterior stiffness averaged 258 N/mm, 51% stiffer than the high displacement posterior stiffness of 171 N/mm. Shear displacement rate had a small effect on the load response, with the 100 mm/s rate causing a mildly stiffer response at low displacements in the anterior direction. Overall, the load-displacement response exhibited pseudo-quadratic behavior at 1 and 10 mm/s but became more linear at 100 mm/s. The shear stiffness in the upper thoracic spine is greatest in the anterior loading direction, being 51%-76% greater than posterior, most likely due to facet interactions. The effect of the shear displacement rate is low.

The effect of end condition on spine segment biomechanics in compression with lateral eccentricity.

During axial impact compression of the cervical spine, injury outcome is highly dependent on initial posture of the spine and the orientation, frictional properties and stiffness of the impact surface. These properties influence the "end condition" the spine experiences in real-world impacts. The effect of end condition on compression and sagittal plane bending in laboratory experiments is well-documented. The spine is able to escape injury in an unconstrained flexion-inducing end condition (e.g. against an angled, low friction surface), but when the end condition is constrained (e.g. head pocketing into a deformable surface) the following torso can compress the aligned spine causing injury. The aim of this study was to determine whether this effect exists under combined axial compression and lateral bending. Over two experimental studies, twenty-four human three vertebra functional spinal units were subjected to controlled dynamic axial compression at two levels of laterally eccentric force and in two end conditions. One end condition allowed the superior spine to laterally rotate and translate (T-Free) and the other end condition allowed only lateral rotation (T-Fixed). Spine kinetics, kinematics, injuries and occlusion of the spinal canal were measured during impact and pre- and post-impact flexibility. In contrast to typical spine responses in flexion-compression loading, the cervical spine specimens in this study did not escape injury in lateral bending when allowed to translate laterally. The specimen group that allowed lateral translation during compression had more injuries at high laterally eccentric force, saw greater peak canal occlusions and post-impact flexibility than constrained specimens.

The Lack of Sex, Age, and Anthropometric Diversity in Neck Biomechanical Data.

Female, elderly, and obese individuals are at greater risk than male, young, and non-obese individuals for neck injury in otherwise equivalent automotive collisions. The development of effective safety technologies to protect all occupants requires high quality data from a range of biomechanical test subjects representative of the population at risk. Here we sought to quantify the demographic characteristics of the volunteers and post-mortem human subjects (PMHSs) used to create the available biomechanical data for the human neck during automotive impacts. A systematic literature and database search was conducted to identify kinematic data that could be used to characterize the neck response to inertial loading or direct head/body impacts. We compiled the sex, age, height, weight, and body mass index (BMI) for 999 volunteers and 110 PMHSs exposed to 5,431 impacts extracted from 63 published studies and three databases, and then compared the distributions of these parameters to reference data drawn from the neck-injured, fatally-injured, and general populations. We found that the neck biomechanical data were biased toward males, the volunteer data were younger, and the PMHS data were older than the reference populations. Other smaller biases were also noted, particularly within female distributions, in the height, weight, and BMI distributions relative to the neck-injured populations. It is vital to increase the diversity of volunteer and cadaveric test subjects in future studies in order to fill the gaps in the current neck biomechanical data. This increased diversity will provide critical data to address existing inequities in automotive and other safety technologies.

Duraplasty in Traumatic Thoracic Spinal Cord Injury: Impact on Spinal Cord Hemodynamics, Tissue Metabolism, Histology, and Behavioral Recovery Using a Porcine Model.

After acute traumatic spinal cord injury (SCI), the spinal cord can swell to fill the subarachnoid space and become compressed by the surrounding dura. In a porcine model of SCI, we performed a duraplasty to expand the subarachnoid space around the injured spinal cord and evaluated how this influenced acute intraparenchymal hemodynamic and metabolic responses, in addition to histological and behavioral recovery. Female Yucatan pigs underwent a T10 SCI, with or without duraplasty. Using microsensors implanted into the spinal cord parenchyma, changes in blood flow (ΔSCBF), oxygenation (ΔPO2), and spinal cord pressure (ΔSCP) during and after SCI were monitored, alongside metabolic responses. Behavioral recovery was tested weekly using the Porcine Injury Behavior Scale (PTIBS). Thereafter, spinal cords were harvested for tissue sparing analyses. In both duraplasty and non-animals, the ΔSCP increased ∼5 mm Hg in the first 6 h post-injury. After this, the SCP appeared to be slightly reduced in the duraplasty animals, although the group differences were not statistically significant after controlling for injury severity in terms of impact force. During the first seven days post-SCI, the ΔSCBF or ΔPO2 values were not different between the duraplasty and control animals. Over 12 weeks, there was no improvement in hindlimb locomotion as assessed by PTIBS scores and no reduction in tissue damage at the injury site in the duraplasty animals. In our porcine model of SCI, duraplasty did not provide any clear evidence of long-term behavioral or tissue sparing benefit after SCI.

Development of a novel, sensitive translational immunoassay to detect plasma glial fibrillary acidic protein (GFAP) after murine traumatic brain injury.

BACKGROUND: Glial fibrillary acidic protein (GFAP) has emerged as a promising fluid biomarker for several neurological indications including traumatic brain injury (TBI), a leading cause of death and disability worldwide. In humans, serum or plasma GFAP levels can predict brain abnormalities including hemorrhage on computed tomography (CT) scans and magnetic resonance imaging (MRI). However, assays to quantify plasma or serum GFAP in preclinical models are not yet available. METHODS: We developed and validated a novel sensitive GFAP immunoassay assay for mouse plasma on the Meso Scale Discovery immunoassay platform and validated assay performance for robustness, precision, limits of quantification, dilutional linearity, parallelism, recovery, stability, selectivity, and pre-analytical factors. To provide proof-of-concept data for this assay as a translational research tool for TBI and Alzheimer's disease (AD), plasma GFAP was measured in mice exposed to TBI using the Closed Head Impact Model of Engineered Rotational Acceleration (CHIMERA) model and in APP/PS1 mice with normal or reduced levels of plasma high-density lipoprotein (HDL). RESULTS: We performed a partial validation of our novel assay and found its performance by the parameters studied was similar to assays used to quantify human GFAP in clinical neurotrauma blood specimens and to assays used to measure murine GFAP in tissues. Specifically, we demonstrated an intra-assay CV of 5.0%, an inter-assay CV of 7.2%, a lower limit of detection (LLOD) of 9.0 pg/mL, a lower limit of quantification (LLOQ) of 24.8 pg/mL, an upper limit of quantification (ULOQ) of at least 16,533.9 pg/mL, dilution linearity of calibrators from 20 to 200,000 pg/mL with 90-123% recovery, dilution linearity of plasma specimens up to 32-fold with 96-112% recovery, spike recovery of 67-100%, and excellent analyte stability in specimens exposed to up to 7 freeze-thaw cycles, 168 h at 4 °C, 24 h at room temperature (RT), or 30 days at - 20 °C. We also observed elevated plasma GFAP in mice 6 h after TBI and in aged APP/PS1 mice with plasma HDL deficiency. This assay also detects GFAP in serum. CONCLUSIONS: This novel assay is a valuable translational tool that may help to provide insights into the mechanistic pathophysiology of TBI and AD.

Neck Muscle and Head/Neck Kinematic Responses While Bracing Against the Steering Wheel During Front and Rear Impacts.

Drivers often react to an impending collision by bracing against the steering wheel. The goal of the present study was to quantify the effect of bracing on neck muscle activity and head/torso kinematics during low-speed front and rear impacts. Eleven seated subjects (3F, 8 M) experienced multiple sled impacts (Δv = 0.77 m/s; apeak = 19.9 m/s2, Δt = 65.5 ms) with their hands on the steering wheel in two conditions: relaxed and braced against the steering wheel. Electromyographic activity in eight neck muscles (sternohyoid, sternocleidomastoid, splenius capitis, semispinalis capitis, semispinalis cervicis, multifidus, levator scapulae, and trapezius) was recorded unilaterally with indwelling electrodes and normalized by maximum voluntary contraction (MVC) levels. Head and torso kinematics (linear acceleration, angular velocity, angular rotation, and retraction) were measured with sensors and motion tracking. Muscle and kinematic variables were compared between the relaxed and braced conditions using linear mixed models. We found that pre-impact bracing generated only small increases in the pre-impact muscle activity (< 5% MVC) when compared to the relaxed condition. Pre-impact bracing did not increase peak neck muscle responses during the impacts; instead it reduced peak trapezius and multifidus muscle activity by about half during front impacts. Bracing led to widespread changes in the peak amplitude and timing of the torso and head kinematics that were not consistent with a simple stiffening of the head/neck/torso system. Instead pre-impact bracing served to couple the torso more rigidly to the seat while not necessarily coupling the head more rigidly to the torso.

The Effect of Compression Applied Through Constrained Lateral Eccentricity on the Failure Mechanics and Flexibility of the Human Cervical Spine.

In contrast to sagittal plane spine biomechanics, little is known about the response of the cervical spine to axial compression with lateral eccentricity of the applied force. This study evaluated the effect of lateral eccentricity on the kinetics, kinematics, canal occlusion, injuries, and flexibility of the cervical spine in translationally constrained axial impacts. Eighteen functional spinal units were subjected to flexibility tests before and after an impact. Impact axial compression was applied at one of three lateral eccentricity levels based on percentage of vertebral body width (low = 5%, medium = 50%, high = 150%). Injuries were graded by dissection. Correlations between intrinsic specimen properties and injury scores were examined for each eccentricity group. Low lateral force eccentricity produced predominantly bone injuries, clinically recognized as compression injuries, while medium and high eccentricity produced mostly contralateral ligament and/or disc injuries, an asymmetric pattern typical of lateral loading. Mean compression force at injury decreased with increasing lateral eccentricity (low = 3098 N, medium = 2337 N, and high = 683 N). Mean ipsilateral bending moments at injury were higher at medium (28.3 N·m) and high (22.9 N·m) eccentricity compared to low eccentricity specimens (0.1 N·m), p < 0.05. Ipsilateral bony injury was related to vertebral body area (VBA) (r = -0.974, p = 0.001) and disc degeneration (r = 0.851, p = 0.032) at medium eccentricity. Facet degeneration was correlated with central bony injury at high eccentricity (r = 0.834, p = 0.036). These results deepen cervical spine biomechanics knowledge in circumstances with coronal plane loads.

A neck compression injury criterion incorporating lateral eccentricity.

There is currently no established injury criterion for the spine in compression with lateral load components despite this load combination commonly contributing to spinal injuries in rollover vehicle crashes, falls and sports. This study aimed to determine an injury criterion and accompanying tolerance values for cervical spine segments in axial compression applied with varying coronal plane eccentricity. Thirty-three human cadaveric functional spinal units were subjected to axial compression at three magnitudes of lateral eccentricity of the applied force. Injury was identified by high-speed video and graded by spine surgeons. Linear regression was used to define neck injury tolerance values based on a criterion incorporating coronal plane loads accounting for specimen sex, age, size and bone density. Larger coronal plane eccentricity at injury was associated with smaller resultant coronal plane force. The level of coronal plane eccentricity at failure appears to distinguish between the types of injuries sustained, with hard tissue structure injuries more common at low levels of eccentricity and soft tissue structure injuries more common at high levels of eccentricity. There was no relationship between axial force and lateral bending moment at injury which has been previously proposed as an injury criterion. These results provide the foundation for designing and evaluating strategies and devices for preventing severe spinal injuries.

An Automated Kinematic Measurement System for Sagittal Plane Murine Head Impacts.

Mild traumatic brain injuries are typically caused by nonpenetrating head impacts that accelerate the skull and result in deformation of the brain within the skull. The shear and compressive strains caused by these deformations damage neural and vascular structures and impair their function. Accurate head acceleration measurements are necessary to define the nature of the insult to the brain. A novel murine head tracking system was developed to improve the accuracy and efficiency of kinematic measurements obtained with high-speed videography. A three-dimensional (3D)-printed marker carrier was designed for rigid fixation to the upper jaw and incisors with an elastic strap around the snout. The system was evaluated by impacting cadaveric mice with the closed head impact model of engineered rotational acceleration (CHIMERA) system using an energy of 0.7 J (5.29 m/s). We compared the performance of the head-marker system to the previously used skin-tracking method and documented significant improvements in measurement repeatability (aggregate coefficient of variation (CV) within raters from 15.8 to 1.5 and between raters from 15.5 to 1.5), agreement (aggregate percentage error from 24.9 to 8.7), and temporal response (aggregate temporal curve agreement from 0.668 to 0.941). Additionally, the new system allows for automated software tracking, which dramatically decreases the analysis time required (74% reduction). This novel head tracking system for mice offers an efficient, reliable, and real-time method to measure head kinematics during high-speed impacts using CHIMERA or other rodent or small mammal head impact models.

Shear stiffness in the lower cervical spine: Effect of sequential posterior element injury.

The aim of this study was to determine the effect of the posterior ligaments and facet joints on the shear stiffness of lower cervical functional spinal units in anterior, posterior, and lateral shear. Five functional spinal units were loaded in anterior, posterior, and right lateral shear up to 100 N using a custom-designed apparatus in a materials testing machine. Specimens were tested in three conditions: intact, with the posterior ligaments severed, and with the facet joints removed. There was a significant decrease in anterior stiffness in the 20-100 N load range from 186 (range: 98-327) N/mm in the intact condition to 105 (range: 78-142) N/mm in the disc-only condition (p = 0.03). Posterior stiffness between these condition decreased significantly from 134 (range: 92-182) N/mm to 119 (range: 83-181) N/mm (p = 0.03). There was no significant effect of posterior ligament removal on shear stiffness. No significant differences were found in the lateral direction or in the 0-20 N range for any direction. Under a 100-N shear load, the facet joints played a significant role in the stiffness of the cervical spine in the anterior-posterior direction, but not in the lateral direction.

Increased severity of the CHIMERA model induces acute vascular injury, sub-acute deficits in memory recall, and chronic white matter gliosis.

Traumatic brain injury (TBI) is a leading cause of death and disability in modern societies. Diffuse axonal and vascular injury are nearly universal consequences of mechanical energy impacting the head and contribute to disability throughout the injury severity spectrum. CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) is a non-surgical, impact-acceleration model of rodent TBI that reliably produces diffuse axonal injury characterized by white matter gliosis and axonal damage. At impact energies up to 0.7 joules, which result in mild TBI in mice, CHIMERA does not produce detectable vascular or grey matter injury. This study was designed to expand CHIMERA's capacity to induce more severe injuries, including vascular damage and grey matter gliosis. This was made possible by designing a physical interface positioned between the piston and animal's head to allow higher impact energies to be transmitted to the head without causing skull fracture. Here, we assessed interface-assisted single CHIMERA TBI at 2.5 joules in wild-type mice using a study design that spanned 6 h-60 d time points. Injured animals displayed robust acute neurological deficits, elevated plasma total tau and neurofilament-light levels, transiently increased proinflammatory cytokines in brain tissue, blood-brain barrier (BBB) leakage and microstructural vascular abnormalities, and grey matter microgliosis. Memory deficits were evident at 30 d and resolved by 60 d. Intriguingly, white matter injury was not remarkable at acute time points but evolved over time, with white matter gliosis being most extensive at 60 d. Interface-assisted CHIMERA thus enables experimental modeling of distinct endophenotypes of TBI that include acute vascular and grey matter injury in addition to chronic evolution of white matter damage, similar to the natural history of human TBI.

Explicit Finite Element Models Accurately Predict Subject-Specific and Velocity-Dependent Kinetics of Sideways Fall Impact.

The majority of hip fractures in the elderly are the result of a fall from standing or from a lower height. Current injury models focus mostly on femur strength while neglecting subject-specific loading. This article presents an injury modeling strategy for hip fractures related to sideways falls that takes subject-specific impact loading into account. Finite element models (FEMs) of the human body were used to predict the experienced load and the femoral strength in a single model. We validated these models for their predicted peak force, effective pelvic stiffness, and fracture status against matching ex vivo sideways fall impacts (n = 11) with a trochanter velocity of 3.1 m/s. Furthermore, they were compared to sideways impacts of volunteers with lower impact velocities that were previously conducted by other groups. Good agreement was found between the ex vivo experiments and the FEMs with respect to peak force (root mean square error [RMSE] = 10.7%, R2 = 0.85) and effective pelvic stiffness (R2 = 0.92, RMSE = 12.9%). The FEMs were predictive of the fracture status for 10 out of 11 specimens. Compared to the volunteer experiments from low height, the FEMs overestimated the peak force by 25% for low BMI subjects and 8% for high BMI subjects. The effective pelvic stiffness values that were derived from the FEMs were comparable to those derived from impacts with volunteers. The force attenuation from the impact surface to the femur ranged between 27% and 54% and was highly dependent on soft tissue thickness (R2 = 0.86). The energy balance in the FEMS showed that at the time of peak force 79% to 93% of the total energy is either kinetic or was transformed to soft tissue deformation. The presented FEMs allow for direct discrimination between fracture and nonfracture outcome for sideways falls and bridge the gap between impact testing with volunteers and impact conditions representative of real life falls. © 2019 American Society for Bone and Mineral Research.