Search

Despite the fundamental importance of understanding impaired brain activity exhibited in post-traumatic epilepsy and other neurological impairments associated with traumatic brain injury (TBI), knowledge of how brain injury affects neuronal activity remains remarkably incomplete. We describe a whole-brain imaging and analysis approach to identify alterations in neuronal activity after TBI as a complementary method to conventional two-dimensional (2D) histological approaches. Here we report an easy-to-follow experimental pipeline to quantify changes in the whole mouse brain using tissue clearing, light sheet microscopy (LSM) and an optimised open-access atlas registration workflow. We validated the outcome of the pipeline using high throughput image analysis software and a secondary atlas registration method. Using the CHIMERA (Closed-Head Impact Model of Engineered Rotational Acceleration) TBI model, TRAP2 mice were subjected to repeated mild TBI or sham treatment followed by tamoxifen injection to lock c-Fos activity after TBI. Brains were SHIELD fixed and passively cleared for imaging of c-Fos+ cells throughout the rostro-caudal axis of the brain using a light sheet microscope equipped with a specialized whole-brain imaging chamber. Volumetric images were stitched and 3D rendered using Arivis Vision4D image analysis software. For quantitative analysis, 2D image stacks were exported to segment c-Fos+ cells and register them to the Allen Mouse Brain Atlas using the BrainQuant3D python package. As a result, c-Fos+ cell counts were estimated throughout the brain and heatmaps were generated. We identified a brain-wide reduction in c-Fos cell density in the TBI group compared to sham controls, indicative of TBI-induced changes in whole brain neuronal activity. Further studies using multi-dimensional imaging coupled with analysis tools will deepen our understanding of post-TBI brain-wide dynamics.

Traumatic brain injury (TBI) in an established risk factor for neurodegenerative disease. In this report, we used the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) to study the effects of a single moderate-severe TBI in rTg4510 mice, a mouse model of tauopathy. Fifteen male rTg4510 mice were impacted at 4.0J at 4-mo of age using interfaced CHIMERA and compared to sham controls. Immediately after injury, moderate-severe TBI induced significant mortality (7/15; 47%), and a prolonged duration of loss of righting reflex. At 2-mo post-injury, surviving mice displayed significant histological evidence of microgliosis (Iba1) and axonal injury (Neurosilver). Western blotting showed that TBI mice had a reduced p-GSK-3β (S9):GSK-3β ratio, suggesting greater tau kinase activity. However, tauopathy in surviving TBI mice showed a divergent response, with 3/8 mice having a very low level of tau protein in brain lysates (i.e. lower than sham), and were thus analyzed separately from the other 5/8 TBI mice that maintained the expected level of total tau. Compared to sham controls, TBI mice with normal tau levels had increased p-tau (PHF1 and AT8), increased autophagolysosome accumulation (p62 and Cathepsin D) and decreased hippocampal size. These findings were not observed in TBI mice with low total tau levels. These observations suggest that TBI leads to chronic white matter injury and altered GSK-3β activity. However, post-injury tauopathy and autophagolysosome accumulation diverged in surviving mice through mechanisms that remain to be defined.

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.

Background Head injury occurs in up to 47% of skiing or snowboarding injuries and is the predominant cause of death in these sports. In most existing literature reporting injury type and prevalence, head injury mechanisms are underreported. Thus, protective equipment design relies on safety evaluation test protocols that are likely oversimplified. This study aims to characterize severity and mechanism of head injuries suffered while skiing and snowboarding in a form appropriate to supplement existing helmet evaluation methods. Methods A 6-year, multicentre, retrospective clinical record review used emergency databases from two major trauma centres and Coroner's reports to identify relevant cases which indicated head impact. Records were investigated to understand the relationships between helmet use, injury type and severity, and injury mechanism. Descriptive statistics and odds ratios aided interpretation of the data. Findings The snow sport head injury database included 766 cases. “Simple fall”, “jump impact” and “impact with object” were the most common injury mechanisms while concussion was observed to be the most common injury type. Compared to “edge catch”, moderate or serious head injury was more common for “fall from height” (OR = 4.69; 95% CI = 1.44–16.23; P = 0.05), “jump impact” (OR = 3.18; 95% CI = 1.48–7.26; P = 0.01) and “impact with object” (OR = 2.44; 95% CI = 1.14–5.56; P = 0.05). Occipital head impact was associated with increased odds of concussion (OR = 7.46; 95% CI = 4.55–12.56; P = 0.001). Interpretation Snow sport head injury mechanisms are complex and cannot be represented through a single impact scenario. By relating clinical data to injury mechanism, improved evaluation methods for protective measures and ultimately better protection can be achieved.

One of the challenges associated with conducting experiments in animal models of traumatic spinal cord injury (SCI) is inducing a consistent injury with minimal variability in the degree of tissue damage and resultant behavioral and biochemical outcomes. We evaluated how the variability in morphometry of the spinal cord and surrounding cerebrospinal fluid (CSF) contributes to the variability in behavioral and histological outcomes in our porcine model of SCI. Using intraoperative ultrasound imaging, spinal cord morphometry was assessed in seven Yucatan minipigs undergoing a weight-drop T10 contusion-compression injury. Bivariate and multi-variate analysis and modeling were used to identify native morphometrical determinants of interanimal variability in histological and behavioral outcomes. The measured biomechanical impact parameters did not correlate with the histological measures or hindlimb locomotor behavior (Porcine Thoracic Injury Behavior Scale). In contrast, clear associations were revealed between CSF layer morphometry and the amount of white matter and tissue sparing. Specifically, the dorsoventral diameter of the dural sac and ventral CSF space were strong predictors of behavioral and histological outcome and together explained ≥95.0% of the variance in these parameters. In addition, a dorsoventral diameter of the spinal cord less than 5.331 mm was a strong contributing factor to poor behavioral recovery over 12 weeks. These results indicate that interanimal variability in cord morphometry provides a potential biological explanation for the observed heterogeneity in histological and behavioral outcomes. Such knowledge is helpful for appropriately balancing experimental groups, and/or varying impact parameters to match cord and CSF layer dimensions for future studies.

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.

Background CT is considered the best method for vertebral fracture detection clinically, but its efficacy in laboratory studies is unknown. Therefore, our objective was to determine the sensitivity, precision, and specificity of high-resolution CT imaging compared to detailed anatomic dissection in an axial compression and lateral bending cervical spine biomechanical injury model. Methods 35 three-vertebra human cadaver cervical spine specimens were impacted in dynamic axial compression (0.5 m/s) at one of three lateral eccentricities (low 5% of the spine transverse diameter, middle 50%, high 150%) and two end conditions (19 constrained lateral translation and 16 unconstrained). All specimens were imaged using high resolution CT imaging (246 μm). Two clinicians (spine surgeon and neuroradiologist) diagnosed the vertebral fractures based on 34 discrete anatomical structures using both the CT images and anatomical dissection. Findings The sensitivity of CT was highest for fractures of the facet joint (59%) and vertebral endplate (57%), and was lowest for pedicle (13%) and lateral mass fractures (23%). The precision of CT was highest for spinous process fractures (83%) and lowest for pedicle (21%), uncinate process and lateral mass (both 23%) fractures. The specificity of CT exceeded 90% for all fractures. The Kappa value between the two reviewers was 0.52, indicating moderate agreement. Interpretation In this in vitro cervical spine injury model, high resolution CT scanning missed many fractures, notably those of the lateral mass and pedicle. This finding is potentially important clinically, as the integrity of these structures is important to clinical stability and surgical fixation planning.

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 (ΔPO

Bone, 125, ISSN:8756-3282

Traumatic brain injury (TBI) affects at least 3 M people annually. In humans, repetitive mild TBI (rmTBI) can lead to increased impulsivity and may be associated with chronic traumatic encephalopathy. To better understand the relationship between repetitive TBI (rTBI), impulsivity and neuropathology, we used CHIMERA (Closed-Head Injury Model of Engineered Rotational Acceleration) to deliver five TBIs to rats, which were continuously assessed for trait impulsivity using the delay discounting task and for neuropathology at endpoint. Compared to sham controls, rats with rTBI displayed progressive impairment in impulsive choice. Histological analyses revealed reduced dopaminergic innervation from the ventral tegmental area to the olfactory tubercle, consistent with altered impulsivity neurocircuitry. Consistent with diffuse axonal injury generated by CHIMERA, white matter inflammation, tau immunoreactivity and degeneration were observed in the optic tract and corpus callosum. Finally, pronounced grey matter microgliosis was observed in the olfactory tubercle. Our results provide insight into the mechanisms by which rTBI leads to post-traumatic psychiatric-like symptoms in a novel rat TBI platform.

Background Head-first impacts with an aligned cervical spine cause some of the most severe types of injuries due to the risk of fractures and associated spinal cord injury. Sports, such as football, mountain biking and horseback riding, contribute to the incidence of spinal cord injury but there is potential to reduce the risk of these injuries through a helmet-mounted device. Methods A novel device, the Pro-Neck-Tor mechanism, was incorporated into a commercial football helmet and tested in head-first impact experiments. The Pro-Neck-Tor connects an inner and outer helmet shell, which upon head-first impact of a certain load, induces motion of the head away from the path of the following torso. Impacts were performed onto three impact surface angles with a flexion-inducing Pro-Neck-Tor mechanism. Findings Based on averaged data, the Pro-Neck-Tor provided a significant and consistent reduction in peak compressive neck forces compared to the unmodified football helmet in the conditions tested. In some impact conditions, the Pro-Neck-Tor increased the peak sagittal plane neck bending moments and impulse over that observed for the unmodified helmet. Interpretation The Pro-Neck-Tor with flexion escape is capable of lowering axial neck forces in head-first impacts compared to a conventional helmet by guiding the cervical column away from an aligned posture and into an eccentric loading scenario which published studies suggests frequently leads to no injury or to a less severe injury. Continued development and testing of the device are needed to optimize the altered neck loading and to drive the design toward a commercial configuration.

Although spinal cord deformation is thought to be a predictor of injury severity, few researchers have investigated dynamic cord deformation, in vivo, during impact. This is needed to establish correlations among impact parameters, internal cord deformation, and histological and functional outcomes. Relying on surface deformations alone may not sufficiently represent spinal cord deformation. The objective of this study was to develop a high-speed fluoroscopic method of tracking the surface and internal cord deformations of rat spinal cord during experimental cord injury. Two radio-opaque beads were injected into the cord at C5/6 in the dorsal and ventral white matter. Four additional beads were glued to the surface of the cord. Dynamic bead displacement was tracked during a dorsal impact (130 mm/sec, 1 mm depth) by high-speed radiographic imaging at 3000 FPS, laterally. The internal spinal cord beads displaced significantly more than the surface beads in the ventral direction (1.1-1.9 times) and more than most surface beads in the cranial direction (1.2-1.5 times). The dorsal beads (internal and surface) displaced more than the ventral beads during all impacts. The bead displacement pattern implies that the spinal cord undergoes complex internal and surface deformations during impact. Residual displacement of the internal beads was significantly greater than that of the surface beads in the cranial-caudal direction but not the dorsoventral direction. Finite element simulation confirmed that the additional bead mass likely had little effect on the internal cord deformations. These results support the merit of this technique for measuring in vivo spinal cord deformation.

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.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.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).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.

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., Journal of the Mechanical Behavior of Biomedical Materials, 126, ISSN:1751-6161, ISSN:1878-0180

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.

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

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.

In this work, we quantify the neck's involvement in stabilizing the head during falls in older adults to avoid head impacts. We tracked kinematics of 12 real-world backward falls in long-term care captured on video, where head impact was avoided. We estimated dynamic spring-dashpot parameters of the neck and hip representing active muscle activity and passive tissue structures. Neck stiffness, damping, and target posture averaged 24.00±6.17Nm/rad, 0.38±0.16Nms/rad, and 76.2±14.7° flexion respectively. The stiffness and target posture suggest that residents actively contracted their neck muscles to maintain the head upright. Our results shed light on the importance of neck strength for avoiding head impact during a fall.Clinical Relevance-Falls account for 80% of traumatic brain injuries in adults 65+ years. While upper limb bracing can reduce the risk of head impacts during a fall in young adults, this protective response is less effective in older adults living in longterm care. Understanding how the neck and torso musculature are used to avoid head impact can guide the design of therapeutic exercise programs and assistive or protective devices.

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 (

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.

Cervical spine injuries often happen in dynamic environments (e.g., sports and motor vehicle crashes) where individuals may be moving their head and neck immediately prior to impact. This motion may reposition the cervical vertebrae in a way that is dissimilar to the upright resting posture that is often used as the initial position in cadaveric studies of catastrophic neck injury. Therefore our aim was to compare the "neutral" cervical alignment measured using fluoroscopy of 11 human subjects while resting in a neutral posture and as their neck passed through neutral during the four combinations of active flexion and extension movements in both an upright and inverted posture. Muscle activation patterns were also measured unilaterally using surface and indwelling electromyography in 8 muscles and then compared between the different conditions. Overall, the head posture, cervical spine alignment and muscle activation levels were significantly different while moving compared to resting upright. Compared to the resting upright condition, average head postures were 6-13° more extended, average vertebral angles varied from 11° more extended to 10° more flexed, and average muscle activation levels varied from unchanged to 10% MVC more active, although the exact differences varied with both direction of motion and orientation. These findings are important for ex vivo testing where the head and neck are statically positioned prior to impact - often in an upright neutral posture with negligible muscle forces - and suggest that current cadaveric head-first impact tests may not reflect many dynamic injury environments.

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.

Hip fractures pose a major health problem throughout the world due to their devastating impact. Current theories for why these injuries are so prevalent in the elderly point to an increased propensity to fall and decreases in bone mass with ageing. However, the fracture mechanisms, particularly the stress and strain conditions leading to bone failure at the hip remain unclear. Here, we directly examined the cortical bone from clinical intra-capsular hip fractures at a microscopic level, and found strong evidence of compression induced failure in the superior cortex. A total of 143 sections obtained from 24 femoral neck samples that were retrieved from 24 fracturing patients at surgery were examined using laser scanning confocal microscopy (LSCM) after fluorescein staining. The stained microcracks showed significantly higher density in the superior cortex than in the inferior cortex, indicating a greater magnitude of strain in the superior femoral neck during the failure-associated deformation and fracture process. The predominant stress state for each section was reconstructed based on the unique correlation between the microcrack pattern and the stress state. Specifically, we found clear evidence of longitudinal compression and buckling as the primary failure mechanisms in the superior cortex. These findings demonstrate the importance of microcrack analysis in studying clinical hip fractures, and point to the central role of the superior cortex failure as an important aspect of the failure initiation in clinical intra-capsular hip fractures.

Despite efforts to simulate the in vivo environment, post-mortem degradation and lack of blood perfusion complicate the use of ex vivo derived material models in computational studies of spinal cord injury. In order to quantify the mechanical changes that manifest ex vivo, the viscoelastic behavior of in vivo and ex vivo porcine spinal cord samples were compared. Stress-relaxation data from each condition were fit to a non-linear viscoelastic model using a novel characterization technique called the direct fit method. To validate the presented material models, the parameters obtained for each condition were used to predict the respective dynamic cyclic response. Both ex vivo and in vivo samples displayed non-linear viscoelastic behavior with a significant increase in relaxation with applied strain. However, at all three strain magnitudes compared, ex vivo samples experienced a higher stress and greater relaxation than in vivo samples. Significant differences between model parameters also showed distinct relaxation behaviors, especially in non-linear relaxation modulus components associated with the short-term response (0.1–1 s). The results of this study underscore the necessity of utilizing material models developed from in vivo experimental data for studies of spinal cord injury, where the time-dependent properties are critical. The ability of each material model to accurately predict the dynamic cyclic response validates the presented methodology and supports the use of the in vivo model in future high-resolution finite element modeling efforts. Statement of Significance Neural tissues (such as the brain and spinal cord) display time-dependent, or viscoelastic, mechanical behavior making it difficult to model how they respond to various loading conditions, including injury. Methods that aim to characterize the behavior of the spinal cord almost exclusively use ex vivo cadaveric or animal samples, despite evidence that time after death affects the behavior compared to that in a living animal (in vivo response). Therefore, this study directly compared the mechanical response of ex vivo and in vivo samples to quantify these differences for the first time. This will allow researchers to draw more accurate conclusions about spinal cord injuries based on ex vivo data (which are easier to obtain) and emphasizes the importance of future in vivo experimental animal work.

The limitations of areal bone mineral density measurements for identifying at-risk individuals have led to the development of alternative screening methods for hip fracture risk including the use of geometrical measurements from the proximal femur and subject specific finite element analysis (FEA) for predicting femoral strength, based on quantitative CT data (qCT). However, these methods need more development to gain widespread clinical applications. This study had three aims: To investigate whether proximal femur geometrical parameters correlate with obtained femur peak force during the impact testing; to examine whether or not failure of the proximal femur initiates in the cancellous (trabecular) bone; and finally, to examine whether or not surface fracture initiates in the places where holes perforate the cortex of the proximal femur. We found that cortical thickness around the trochanteric-fossa is significantly correlated to the peak force obtained from simulated sideways falling (R 2 = 0.69) more so than femoral neck cortical thickness (R 2 = 0.15). Dynamic macro level FE simulations predicted that fracture generally initiates in the cancellous bone compartments. Moreover, our micro level FEA results indicated that surface holes may be involved in primary failure events.

MINI: Identifying fracture is important for understanding vertebral mechanics. Isolated cadaveric thoracolumbar vertebrae were compressed, and surface strains were measured using digital image correlation. Fracture locations from video analysis were qualitatively similar to the locations of high compressive strains and local damage occurred before the maximum force was reached. STUDY DESIGN Ex vivo compression experiments on isolated cadaveric vertebrae. OBJECTIVE To qualitatively compare the fracture locations identified in video analysis with the locations of high compressive strain measured with digital image correlation (DIC) on vertebral bodies and to evaluate the timing of local damage to the cortical shell relative to the global yield force. SUMMARY OF BACKGROUND DATA In previous ex vivo experiments, cortical bone fracture has been identified using various methods including acoustic emission sensors, strain gages, video analysis, or force signals. These methods are, however, limited in their ability to detect the location and timing of fracture. We propose use of DIC, a noncontact optical technique that measures surface displacement, to quantify variables related to damage. METHODS Isolated thoracolumbar human cadaveric vertebral bodies (n = 6) were tested in compression to failure at a quasi-static rate, and the force applied was measured using a load cell. The surface displacement and strain were measured using DIC. Video analysis was performed to identify fractures. RESULTS The location of fractures identified in the video corresponded well with the locations of high compressive strain on the bone. Before reaching the global yield force, more than 10% of the DIC measurements reached a minimum principal strain of 1.0%, a previously reported threshold for cortical bone damage. CONCLUSION DIC measurements provide an objective measure that can be used to identify the location and timing of fractures during ex vivo vertebral experiments. This is important for understanding fracture mechanics and for validating vertebral computational models that incorporate failure. LEVEL OF EVIDENCE N /A.

In the military environment, injured soldiers undergoing medical evacuation via helicopter or mine-resistant ambush-protected vehicle (MRAP) are subjected to vibration and shock inherent to the transport vehicle. We conducted the present study to assess the consequences of such vibration on the acutely injured spinal cord. We used a porcine model of spinal cord injury (SCI). After a T10 contusion-compression injury, animals were subjected to 1) no vibration (n = 7-8), 2) whole body vibration at frequencies and amplitudes simulating helicopter transport (n = 8), or 3) whole body vibration simulating ground transportation in an MRAP ambulance (n = 7). Hindlimb locomotor function (using Porcine Thoracic Injury Behavior Scale [PTIBS]), Eriochrome Cyanine histochemistry and biochemical analysis of inflammatory and neural damage markers were analyzed. Cerebrospinal fluid (CSF) expression levels for monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, IL-8, and glial fibrillary acidic protein (GFAP) were similar between the helicopter or MRAP group and the unvibrated controls. Spared white/gray matter tended to be lower in the MRAP-vibrated animals than in the unvibrated controls, especially rostral to the epicenter. However, spared white/gray matter in the helicopter-vibrated group appeared normal. Although there was a relationship between the extent of sparing and the extent of locomotor recovery, no significant differences were found in PTIBS scores between the groups. In summary, exposures to vibration in the context of ground (MRAP) or aeromedical (helicopter) transportation did not significantly impair functional outcome in our large animal model of SCI. However, MRAP vibration was associated with increased tissue damage around the injury site, warranting caution around exposure to vehicle vibration acutely after SCI.

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.

Standards for sports headgear were introduced as far back as the 1960s and many have remained substantially unchanged to present day. Since this time, headgear has virtually eliminated catastrophic head injuries such as skull fractures and changed the landscape of head injuries in sports. Mild traumatic brain injury (mTBI) is now a prevalent concern and the effectiveness of headgear in mitigating mTBI is inconclusive for most sports. Given that most current headgear standards are confined to attenuating linear head mechanics and recent brain injury studies have underscored the importance of angular mechanics in the genesis of mTBI, new or expanded standards are needed to foster headgear development and assess headgear performance that addresses all types of sport-related head and brain injuries. The aim of this review was to provide a basis for developing new sports headgear impact tests for standards by summarizing and critiquing the following: (1) impact testing procedures currently codified in published headgear standards for sports and (2) new or proposed headgear impact test procedures in published literature and/or relevant conferences. Research areas identified as needing further knowledge to support standards test development include defining sports-specific head impact conditions, establishing injury and age appropriate headgear assessment criteria, and the development of headgear specific head and neck surrogates for at-risk populations.

Computational models of the human brain are widely used in the evaluation and development of helmets and other protective equipment. These models are often attempted to be validated using cadaver tissue displacements despite studies showing neural tissue degrades quickly after death. Addressing this limitation, this study aimed to develop a technique for quantifying living brain motion in vivo using a closed head impact animal model of traumatic brain injury (TBI) called CHIMERA. We implanted radiopaque markers within the brain of three adult ferrets and resealed the skull while the animals were anesthetized. We affixed additional markers to the skull to track skull kinematics. The CHIMERA device delivered controlled, repeatable head impacts to the head of the animals while the impacts were fluoroscopically stereo-visualized. We observed that 1.5 mm stainless steel fiducials (∼8 times the density of the brain) migrated from their implanted positions while neutral density targets remained in their implanted position post-impact. Brain motion relative to the skull was quantified in neutral density target tests and showed increasing relative motion at higher head impact severities. We observed the motion of the brain lagged behind that of the skull, similar to previous studies. This technique can be used to obtain a comprehensive dataset of in vivo brain motion to validate computational models reflecting the mechanical properties of the living brain. The technique would also allow the mechanical response of in vivo brain tissue to be compared to cadaveric preparations for investigating the fidelity of current human computational brain models.

Background: The annual incidence of traumatic brain injury (TBI) in the United States is over 2.5 million, with approximately 3–5 million people living with chronic sequelae. Compared with moderate-severe TBI, the long-term effects of mild TBI (mTBI) are less understood but important to address, particularly for contact sport athletes and military personnel who have high mTBI exposure. The purpose of this study was to determine the behavioural and neuropathological phenotypes induced by the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA) model of mTBI in both wild-type (WT) and APP/PS1 mice up to 8 months post-injury. Methods: Male WT and APP/PS1 littermates were randomized to sham or repetitive mild TBI (rmTBI; 2 × 0.5 J impacts 24 h apart) groups at 5.7 months of age. Animals were assessed up to 8 months post-injury for acute neurological deficits using the loss of righting reflex (LRR) and Neurological Severity Score (NSS) tasks, and chronic behavioural changes using the passive avoidance (PA), Barnes maze (BM), elevated plus maze (EPM) and rotarod (RR) tasks. Neuropathological assessments included white matter damage; grey matter inflammation; and measures of Aβ levels, deposition, and aducanumab binding activity. Results: The very mild CHIMERA rmTBI conditions used here produced no significant acute neurological or motor deficits in WT and APP/PS1 mice, but they profoundly inhibited extinction of fear memory specifically in APP/PS1 mice over the 8-month assessment period. Spatial learning and memory were affected by both injury and genotype. Anxiety and risk-taking behaviour were affected by injury but not genotype. CHIMERA rmTBI induced chronic white matter microgliosis, axonal injury and astrogliosis independent of genotype in the optic tract but not the corpus callosum, and it altered microgliosis in APP/PS1 amygdala and hippocampus. Finally, rmTBI did not alter long-term tau, Aβ or amyloid levels, but it increased aducanumab binding activity. Conclusions: CHIMERA is a useful model to investigate the chronic consequences of rmTBI, including behavioural abnormalities consistent with features of post-traumatic stress disorder and inflammation of both white and grey matter. The presence of human Aβ greatly modified extinction of fear memory after rmTBI.

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.

During traumatic spinal cord injury (SCI), the spinal cord is subject to external displacements that result in damage of neural tissues. These displacements produce complex internal deformations, or strains, of the spinal cord parenchyma. The aim of this study is to determine a relationship between these internal strains during SCI and primary damage to spinal cord gray matter (GM) in an in vivo rat contusion model. Using magnetic resonance imaging and novel image registration methods, we measured three-dimensional (3D) mechanical strain in in vivo rat cervical spinal cord (n = 12) during an imposed contusion injury. We then assessed expression of the neuronal transcription factor, neuronal nuclei (NeuN), in ventral horns of GM (at the epicenter of injury as well as at intervals cranially and caudally), immediately post-injury. We found that minimum principal strain was most strongly correlated with loss of NeuN stain across all animals (R2 = 0.19), but varied in strength between individual animals (R2 = 0.06–0.52). Craniocaudal distribution of anatomical damage was similar to measured strain distribution. A Monte Carlo simulation was used to assess strain field error, and minimum principal strain (which ranged from 8% to 36% in GM ventral horns) exhibited a standard deviation of 2.6% attributed to the simulated error. This study is the first to measure 3D deformation of the spinal cord and relate it to patterns of ensuing tissue damage in an in vivo model. It provides a platform on which to build future studies addressing the tolerance of spinal cord tissue to mechanical deformation.

– WeBWorK is a widely-used open-source, online homework tool where instructors may author their own problems, or select problems from an Open Problem Library. While it is extensively and globally used in mathematics, there are few problems available for engineering subjects. Due to initial student feedback based on mathematics problems, we decided to compare WeBWorK directly to our Blackboard Learn LMS for online homework during an integrated second-year Mechanical Engineering program. Students were assigned two problem sets in Blackboard and two problem sets in WeBWorK, and then completed a survey. Results show a strong preference for WeBWorK in all areas, including ease of use, ease of navigation, clear feedback, reported enhancement of learning, etc. We outline the primary benefits and drawbacks of using WeBWorK, and conclude by recommending WeBWorK for online homework in engineering courses.

The spinal cord undergoes physical deformation during traumatic spinal cord injury (TSCI), which results in biological damage. This study demonstrates a novel approach, using magnetic resonance imaging and image registration techniques, to quantify the three-dimensional deformation of the cervical spinal cord in an in vivo rat model. Twenty-four male rats were subjected to one of two clinically relevant mechanisms of TSCI (i.e. contusion and dislocation) inside of a MR scanner using a novel apparatus, enabling imaging of the deformed spinal cords. The displacement fields demonstrated qualitative differences between injury mechanisms. Three-dimensional Lagrangian strain fields were calculated, and the results from the contusion injury mechanism were deemed most reliable. Strain field error was assessed using a Monte Carlo approach, which showed that simulated normal strain error experienced a bias, whereas shear strain error did not. In contusion injury, a large region of dorso-ventral compressive strain was observed under the impactor which extended into the ventral region of the spinal cord. High tensile lateral strains under the impactor and compressive lateral strains in the lateral white matter were also observed in contusion. The ability to directly observe and quantify in vivo spinal cord deformation informs our knowledge of the mechanics of TSCI.