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BACKGROUND: Prior research and experience has increased physician understanding of infant skull fracture prediction. However, patterns related to fracture length, nonlinearity, and features of complexity remain poorly understood, and differences across infant age groups have not been previously explored. METHODS: To determine how infant and low-height fall characteristics influence fracture patterns, we collected data from 231 head CT 3D reconstructions and quantified length and nonlinearity using a custom image processing code. Regression analysis was used to determine the effects of age and fall characteristics on nonlinearity, length, and features of fracture complexity. RESULTS: While impact surface had an important role in the number of cracks present in a fracture, younger infants and greater fall heights significantly affected most features of fracture complexity, including suture-to-suture spanning and biparietal involvement. In addition, increasing fracture length with increasing fall height supports trends identified by prior finite-element modeling. Finally, this study yielded results supporting the presence of soft tissue swelling as a function of fracture location rather than impact site. CONCLUSIONS: Age-related properties of the infant skull confer unique fracture patterns following head impact. Further characterization of these properties, particularly in infants <4 months of age, will improve our understanding of the infant skull's response to trauma. IMPACT: Younger infant age and greater fall heights have significant effects on many features of fracture complexity resulting from low-height falls. Incorporating multiple crack formation and multiple bone involvement into computational models of young infant skull fractures may result in increased biofidelity. Drivers of skull fracture complexity are not well understood, and skull fracture patterns in real-world data across infant age groups have not been previously described. Understanding fracture complexity relative to age in accidental falls will improve the understanding of accidental and abusive head trauma.
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Traumatismos Craniocerebrais , Fraturas Cranianas , Humanos , Lactente , Acidentes por Quedas , Fraturas Cranianas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Cabeça , CrânioRESUMO
Computational models of infant head impact are limited by the paucity of infant cranial bone material property data, particularly with regard to the anisotropic relationships created by the trabecular fibers in infant bone. We previously reported high-rate material property data for human infant cranial bone tested perpendicular to trabeculae fiber orientation. In this study, we measure the anisotropic properties of human infant cranial bone by analyzing bending modulus parallel to the trabeculae fibers. We tested human bone specimens from nine donors ranging in age from 32 weeks gestational age to 10 months at strain rates of 12.3-30.1 s-1. Bending modulus significantly increased with donor age (p=0.008) and was 13.4 times greater along the fiber direction compared to perpendicular to the fibers. Ultimate stress was greater by 5.1 times when tested parallel to the fibers compared to perpendicular (p=0.067). Parietal bone had a higher modulus and ultimate stress compared to occipital bone, but this trend was not significant, as previously shown perpendicular to fiber orientation. Combined, these data suggest that the pediatric skull is highly age-dependent, anisotropic, and regionally dependent. The incorporation of these characteristics in finite element models of infant head impact will be necessary to advance pediatric head injury research and further our understanding of the mechanisms of head injury in children.
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Osso OccipitalRESUMO
Skull fracture is a common finding for both accidental and abusive head trauma in infants and young children, and may provide important clues as to the energy and directionality of the event leading to the skull fracture. However, little is understood regarding the mechanics of skull fracture in the pediatric skull, and how accidental fall parameters contribute to skull fracture patterns. The objectives of this research were to utilize a newly developed linear elastic fracture mechanics finite element model of infant skull fracture to investigate the effect of impact angle and fall height on the predictions of skull fracture patterns in infants. Nine impact angles of right parietal bone impacts were simulated from three different heights onto a rigid plate. The average ± standard deviation of the distance between the impact location and fracture initiation site was 8.0 ± 5.9 mm. Impact angle significantly affected the fracture initiation site (p < 0.0001) and orientation (p < 0.0001). A 15 deg variation in impact angle changed the initiation site up to 47 mm. The orientation of the fracture pattern was dependent on the impact location and ran either horizontal or vertical toward the ossification center of the bone. Fall height significantly affected the fracture length (p = 0.0356). Specifically, at the same impact angle, a 0.3 m increase in fall height increased the skull fracture length by 21.39 ± 34.26 mm. These data indicate that environmental variability needs to be carefully considered when evaluating infant skull fracture patterns from low-height falls.
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Acidentes por QuedasRESUMO
Traumatic brain injury (TBI) is a common injury modality affecting a diverse patient population. Axonal injury occurs when the brain experiences excessive deformation as a result of head impact. Previous studies have shown that the arachnoid trabeculae (AT) in the subarachnoid space significantly influence the magnitude and distribution of brain deformation during impact. However, the quantity and spatial distribution of cranial AT in humans is unknown. Quantification of these microstructural features will improve understanding of force transfer during TBI, and may be a valuable dataset for microneurosurgical procedures. In this study, we quantify the spatial distribution of cranial AT in seven post-mortem human subjects. Optical coherence tomography (OCT) was used to conduct in situ imaging of AT microstructure across the surface of the human brain. OCT images were segmented to quantify the relative amounts of trabecular structures through a volume fraction (VF) measurement. The average VF for each brain ranged from 22.0% to 29.2%. Across all brains, there was a positive spatial correlation, with VF significantly greater by 12% near the superior aspect of the brain (p < .005), and significantly greater by 5%-10% in the frontal lobes (p < .005). These findings suggest that the distribution of AT between the brain and skull is heterogeneous, region-dependent, and likely contributes to brain deformation patterns. This study is the first to image and quantify human AT across the cerebrum and identify region-dependencies. Incorporation of this spatial heterogeneity may improve the accuracy of computational models of human TBI and enhance understanding of brain dynamics.
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Aracnoide-Máter/anatomia & histologia , Encéfalo/anatomia & histologia , Pia-Máter/anatomia & histologia , Crânio/anatomia & histologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aracnoide-Máter/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pia-Máter/diagnóstico por imagem , Crânio/diagnóstico por imagem , Tomografia de Coerência ÓpticaRESUMO
Skull fractures are common injuries in young children, typically caused by accidental falls and child abuse. The paucity of detailed biomechanical data from real-world trauma in children has hampered development of biomechanical thresholds for skull fracture in infants. The objectives of this study were to identify biomechanical metrics to predict skull fracture, determine threshold values associated with fracture, and develop skull fracture risk curves for low-height falls in infants. To achieve these objectives, we utilized an integrated approach consisting of case evaluation, anthropomorphic reconstruction, and finite element simulation. Four biomechanical candidates for predicting skull fracture were identified (first principal stress, first principal strain, shear stress, and von Mises stress) and evaluated against well-witnessed falls in infants (0-6 months). Among the predictor candidates, first principal stress and strain correlated best with the occurrence of parietal skull fracture. The principal stress and strain thresholds associated with 50 and 95% probability of parietal skull fracture were 25.229 and 36.015 MPa and 0.0464 and 0.0699, respectively. Risk curves using these predictors determined that infant falls from 0.3 m had a low probability (0-54%) to result in parietal skull fracture, particularly with carpet impact (0-1%). Head-first falls from 0.9 m had a high probability of fracture (86-100%) for concrete impact and a moderate probability (34-81%) for carpet impact. Probabilities of fracture in 0.6 m falls were dependent on impact surface. Occipital impacts from 0.9 m onto the concrete also had the potential (27-90% probability) to generate parietal skull fracture. These data represent a multi-faceted biomechanical assessment of infant skull fracture risk and can assist in the differential diagnosis for head trauma in children.
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Acidentes por Quedas , Fenômenos Biomecânicos , Medição de Risco , Fraturas Cranianas/patologia , Maus-Tratos Infantis/diagnóstico , Diagnóstico Diferencial , Feminino , Análise de Elementos Finitos , Medicina Legal , Humanos , Lactente , Recém-Nascido , Masculino , Manequins , Probabilidade , Fraturas Cranianas/etiologia , Estresse Fisiológico , Propriedades de SuperfícieRESUMO
BACKGROUND: The classic metaphyseal lesion (CML) is strongly associated with infant abuse, but the biomechanics responsible for this injury have not been rigorously studied. Radiologic and CT-pathological correlates show that the distal tibial CML always involves the cortex near the subperiosteal bone collar, with variable extension of the fracture into the medullary cavity. Therefore, it is reasonable to assume that the primary site of bone failure is cortical, rather than intramedullary. OBJECTIVE: This study focuses on the strain patterns generated from finite element modeling to identify loading scenarios and regions of the cortex that are susceptible to bone failure. MATERIALS AND METHODS: A geometric model was constructed from a normal 3-month-old infant's distal tibia and fibula. The model's boundary conditions were set to mimic forceful manipulation of the ankle with eight load modalities (tension, compression, internal rotation, external rotation, dorsiflexion, plantar flexion, valgus bending and varus bending). RESULTS: For all modalities except internal and external rotation, simulations showed increased cortical strains near the subperiosteal bone collar. Tension generated the largest magnitude of cortical strain (24%) that was uniformly distributed near the subperiosteal bone collar. Compression generated the same distribution of strain but to a lesser magnitude overall (15%). Dorsiflexion and plantar flexion generated high (22%) and moderate (14%) localized cortical strains, respectively, near the subperiosteal bone collar. Lower cortical strains resulted from valgus bending, varus bending, internal rotation and external rotation (8-10%). The highest valgus and varus bending cortical strains occurred medially. CONCLUSION: These simulations suggest that the likelihood of the initial cortical bone failure of the CML is higher along the margin of the subperiosteal bone collar when the ankle is under tension, compression, valgus bending, varus bending, dorsiflexion and plantar flexion, but not under internal and external rotation. Focal cortical strains along the medial margins of the subperiosteal bone collar with varus and valgus bending may explain the known tendency for focal distal tibial CMLs to occur medially. Further research is needed to determine the threshold of applied forces required to produce this strong indicator of infant abuse.
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Fíbula/diagnóstico por imagem , Fíbula/fisiologia , Análise de Elementos Finitos , Tíbia/diagnóstico por imagem , Tíbia/fisiologia , Microtomografia por Raio-X , Fenômenos Biomecânicos , Humanos , Lactente , Modelos Anatômicos , Estresse MecânicoRESUMO
Vitreous collagen structure plays an important role in ocular mechanics. However, capturing this structure with existing vitreous imaging methods is hindered by the loss of sample position and orientation, low resolution, or a small field of view. The objective of this study was to evaluate confocal reflectance microscopy as a solution to these limitations. Intrinsic reflectance avoids staining, and optical sectioning eliminates the requirement for thin sectioning, minimizing processing for optimal preservation of the natural structure. We developed a sample preparation and imaging strategy using ex vivo grossly sectioned porcine eyes. Imaging revealed a network of uniform diameter crossing fibers (1.1 ± 0.3 µm for a typical image) with generally poor alignment (alignment coefficient = 0.40 ± 0.21 for a typical image). To test the utility of our approach for detecting differences in fiber spatial distribution, we imaged eyes every 1 mm along an anterior-posterior axis originating at the limbus and quantified the number of fibers in each image. Fiber density was higher anteriorly near the vitreous base, regardless of the imaging plane. These data demonstrate that confocal reflectance microscopy addresses the previously unmet need for a robust, micron-scale technique to map features of collagen networks in situ across the vitreous.
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Vitreoretinal mechanics plays an important role in retinal trauma and many sight-threatening diseases. In age-related pathologies, such as posterior vitreous detachment and vitreomacular traction, lingering vitreoretinal adhesions can lead to macular holes, epiretinal membranes, retinal tears and detachment. In age-related macular degeneration, vitreoretinal traction has been implicated in the acceleration of the disease due to the stimulation of vascular growth factors. Despite this strong mechanobiological influence on trauma and disease in the eye, fundamental understanding of the mechanics at the vitreoretinal interface is limited. Clarification of adhesion mechanisms and the role of vitreoretinal mechanics in healthy eyes and disease is necessary to develop innovative treatments for these pathologies. In this review, we evaluate the existing literature on the structure and function of the vitreoretinal interface to gain insight into age- and region-dependent mechanisms of vitreoretinal adhesion. We explore the role of vitreoretinal adhesion in ocular pathologies to identify knowledge gaps and future research areas. Finally, we recommend future mechanics-based studies to address the critical needs in the field, increase fundamental understanding of vitreoretinal mechanisms and disease, and inform disease treatments.
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Perfurações Retinianas , Corpo Vítreo , Humanos , Perfurações Retinianas/patologia , Aderências Teciduais , Corpo Vítreo/patologiaRESUMO
Traumatic brain injury (TBI) is a significant problem in global health that affects a wide variety of patients. Mild forms of TBI, commonly referred to as concussion, are a result of rapid accelerations of the head from either direct or indirect impacts. Kinetic energy from the impact is transferred into deformation of the brain, leading to cellular disruption. This transfer of energy is in part mediated by the pia-arachnoid complex (PAC), a layer of anatomical structures that forms the physical connection between the brain and the skull. The importance of properly quantifying the mechanics of the PAC for use in computational models of TBI has been understood for some time, but data from human subjects has been unavailable. In this study, we quantify the normal traction modulus of the PAC in five post-mortem human subjects using hydrostatic fluid pressurization in combination with optical coherence tomography. Testing at multiple locations across each brain reveals that brain-skull stiffness is heterogeneously distributed. The material response to traction loading was linear, with a mean normal traction modulus of 12.6 ± 4.8 kPa. Modulus was 21% greater in superior regions of the brain compared to inferior regions. Comparisons with regional microstructural data suggests a potential relationship between the volume fraction of arachnoid trabeculae and modulus. Comparisons to coincident measurements of microstructural properties showed a positive correlation between arachnoid membrane thickness and normal traction modulus. This study is the first to characterize the mechanics of the human pia-arachnoid complex and quantify material properties in situ. These findings suggest implementing a heterogeneous model of the brain-skull interface in computational models of TBI may lead to more realistic injury prediction.
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Aracnoide-Máter , Pia-Máter , Encéfalo , Cabeça , Humanos , CrânioRESUMO
Sex, head and neck posture, and cervical muscle preparation are contributing factors in the severity of head and neck injuries. However, it is unknown how these factors modulate the head kinematics. In this study, twenty-four (16 male and 8 female) participants experienced 50 impulsive forces to their heads with and without an acoustic warning. Female participants demonstrated a 71 ms faster (p = 0.002) muscle activation onset compared to males after warning. The magnitude of muscle activation was not significant between sexes. Females exhibited 21% (p < 0.008) greater peak angular velocity in all force directions and 18% (p < 0.04) greater peak angular acceleration in sagittal plane compared to males. Females exhibited 15% (p = 0.03) greater peak linear acceleration compared to males only in sagittal flexion. Preparation attenuated head kinematics significantly (p < 0.03) in 11 out of 18 investigated head kinematics for both sexes. A warning eliciting a startle response 420 ms prior to the impact resulted in significant attenuation of all measured head kinematics in sagittal extension (p < 0.037). In conclusion, both sex and warning type were significant factors in head kinematics. These data provide insight into the complex relationship of muscle activation and sex, and may help identify innovative strategies to reduce head and neck injury risk in sports.
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Traumatismos Craniocerebrais/fisiopatologia , Lesões do Pescoço/fisiopatologia , Músculos do Pescoço/fisiologia , Reflexo de Sobressalto/fisiologia , Aceleração , Acústica , Fatores Etários , Traumatismos em Atletas/fisiopatologia , Fenômenos Biomecânicos , Eletromiografia , Feminino , Humanos , Masculino , Contração Muscular , Pescoço/anatomia & histologia , Músculos do Pescoço/anatomia & histologia , Postura/fisiologiaRESUMO
Head trauma is the leading cause of death and debilitating injury in children. Computational models are important tools used to understand head injury mechanisms but they must be validated with experimental data. In this communication we present in situ measurements of brain deformation during rapid, nonimpact head rotation in juvenile pigs of different ages. These data will be used to validate computational models identifying age-dependent thresholds of axonal injury. Fresh 5 days (n=3) and 4 weeks (n=2) old piglet heads were transected horizontally and secured in a container. The cut surface of each brain was marked and covered with a transparent, lubricated plate that allowed the brain to move freely in the plane of rotation. For each brain, a rapid (20-28 ms) 65 deg rotation was applied sequentially at 50 rad/s, 75 rad/s, and 75 rad/s. Each rotation was digitally captured at 2500 frames/s (480x320 pixels) and mark locations were tracked and used to compute strain using an in-house program in MATLAB. Peak values of principal strain (E(peak)) were significantly larger during deceleration than during acceleration of the head rotation (p<0.05), and doubled with a 50% increase in velocity. E(peak) was also significantly higher during the second 75 rad/s rotation than during the first 75 rad/s rotation (p<0.0001), suggesting structural alteration at 75 rad/s and the possibility that similar changes may have occurred at 50 rad/s. Analyzing only lower velocity (50 rad/s) rotations, E(peak) significantly increased with age (16.5% versus 12.4%, p<0.003), which was likely due to the larger brain mass and smaller viscoelastic modulus of the 4 weeks old pig brain compared with those of the 5 days old. Strain measurement error for the overall methodology was estimated to be 1%. Brain tissue strain during rapid, nonimpact head rotation in the juvenile pig varies significantly with age. The empirical data presented will be used to validate computational model predictions of brain motion under similar loading conditions and to assist in the development of age-specific thresholds for axonal injury. Future studies will examine the brain-skull displacement and will be used to validate brain-skull interactions in computational models.
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Encéfalo/fisiologia , Movimentos da Cabeça/fisiologia , Modelos Neurológicos , Animais , Animais Recém-Nascidos , Simulação por Computador , Módulo de Elasticidade/fisiologia , Dureza , Rotação , SuínosRESUMO
Purpose: In this experimental study, we quantify retinal microvasculature morphological features with depth, region, and age in immature and mature ovine eyes. These data identify morphological vulnerabilities in young eyes to inform the mechanics of retinal hemorrhage in children. Methods: Retinal specimens from the equator and posterior pole of preterm (n = 4) and adult (n = 9) sheep were imaged using confocal microscopy. Vessel segment length, diameter, angular asymmetry, tortuosity, and branch points were quantified using a custom image segmentation code. Significant differences were identified through two-way ANOVAs and correlation analyses. Results: Vessel segment lengths were significantly shorter in immature eyes compared to adults (P < 0.003) and were significantly shorter at increasing depths in the immature retina (P < 0.04). Tortuosity significantly increased with depth, regardless of age (P < 0.05). These data suggest a potential vulnerability of vasculature in the deeper retinal layers, particularly in immature eyes. Preterm retina had significantly more branch points than adult retina in both the posterior pole and equator, and the number increased significantly with depth (P < 0.001). Conclusions: The increased branch points and decreased segment lengths in immature microvasculature suggest that infants will experience greater stress and strain during traumatic loading compared to adults. The increased morphological vulnerability of the immature microvasculature in the deeper layers of the retina suggest that intraretinal hemorrhages have a greater likelihood of occurring from trauma compared to preretinal hemorrhages. The morphological features captured in this study lay the foundation to explore the mechanics of retinal hemorrhage in infants and identify vulnerabilities that explain patterns of retinal hemorrhage in infants.
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Hemorragia Retiniana/patologia , Vasos Retinianos/anatomia & histologia , Envelhecimento/patologia , Envelhecimento/fisiologia , Animais , Animais Recém-Nascidos , Artérias/anormalidades , Artérias/patologia , Artérias/fisiopatologia , Fenômenos Biomecânicos , Feminino , Humanos , Instabilidade Articular/patologia , Instabilidade Articular/fisiopatologia , Microscopia Confocal , Microvasos/anatomia & histologia , Microvasos/fisiologia , Variações Dependentes do Observador , Hemorragia Retiniana/etiologia , Vasos Retinianos/fisiologia , Ovinos , Dermatopatias Genéticas/patologia , Dermatopatias Genéticas/fisiopatologia , Malformações Vasculares/patologia , Malformações Vasculares/fisiopatologiaRESUMO
Infant skull fractures are common in both accidental and abusive head trauma, but identifying the cause of injury may be challenging without adequate evidence. To better understand the mechanics of infant skull fracture and identify environmental variables that lead to certain skull fracture patterns, we developed an innovative computational framework that utilizes linear elastic fracture mechanics theory to predict skull fracture as a first step to study this problem. The finite element method and adaptive-remeshing technique were employed to simulate high-fidelity, geometrically explicit crack propagation in an infant skull following impact. In the framework, three modes of stress intensity factors are calculated by means of the M-integral using the commercial analysis code, FRANC3D, and are used as measures of crack driving force. The anisotropy of infant skulls is represented by means of a transversely isotropic constitutive model and a direction-dependent fracture-toughness locus. The ability of the framework to predict impact-induced fracture patterns is validated by comparison with experimentally observed fracture patterns from the literature.
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Algoritmos , Fraturas Cranianas/diagnóstico , Simulação por Computador , Humanos , Lactente , Estresse MecânicoRESUMO
Drug-loaded hydrogel devices are emerging as an effective means of localized and sustained drug delivery for the treatment of corneal conditions and injuries. One such device uses a novel, thiolated crosslinked carboxymethylated, hyaluronic acid-based hydrogel (CMHA-S) film to deliver drug to the ocular surface upon placement into the inferior fornix of the eye. While proven to be very safe and effective, the CMHA-S film tends to dislodge in the highly-lubricated ocular environment, thereby reducing drug delivery efficiency and drug efficacy. In this study, we used a three-dimensional computational finite element model of the eye to determine the effect of geometry and surface friction on film retention in the inferior fornix, and to evaluate multiple geometrical film designs. Retention of the film was dependent on geometry and on the friction ratio of the film to the eyelid and globe. These effects were interactive. When the ratio of friction on the lid side to the globe side of the film was low, geometry played a large role in the film's displacement. When this ratio was high, differences in displacement due to geometry were negligible. The optimal relationship of friction between the film and its eyelid-side and globe-side surfaces was found to be linear with at least 1.4 times greater friction required on the eyelid-side for immobilization. A geometry similar to a half cylinder was found to be most effective with this friction ratio in retaining the film in the inferior fornix and in contact with the globe. Other geometries will likely require other friction ratios. In summary, CMHA-S film retention can be achieved through simple modifications of geometry and manipulation of surface interaction with the eye.
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Sistemas de Liberação de Medicamentos/métodos , Ácido Hialurônico/química , Hidrogéis/química , Membranas Artificiais , Modelos Químicos , Análise de Elementos FinitosRESUMO
While several studies have qualitatively investigated age- and region-dependent adhesion between the vitreous and retina, no studies have directly measured the vitreoretinal strength of adhesion. In this study, we developed a rotational peel device and associated methodology to measure the maximum and steady-state peel forces between the vitreous and the retina. Vitreoretinal adhesion in the equator and posterior pole were measured in human eyes from donors ranging 30 to 79 years of age, and in sheep eyes from premature, neonatal, young lamb, and young adult sheep. In human eyes, maximum peel force in the equator (7.24 ± 4.13 mN) was greater than in the posterior pole (4.08 ± 2.03 mN). This trend was especially evident for younger eyes from donors 30 to 39 years of age. After 60 years of age, there was a significant decrease in the maximum equatorial (4.69 ± 2.52 mN, p = 0.016) and posterior pole adhesion (2.95 ± 1.25 mN, p = 0.037). In immature sheep eyes, maximum adhesion was 7.60 ± 3.06 mN, and did not significantly differ between the equator and posterior pole until young adulthood. At this age, the maximum adhesion in the equator nearly doubled (16.67 ± 7.45 mN) that of the posterior pole, similar to the young adult human eyes. Light microscopy images suggest more disruption of the inner limiting membrane (ILM) in immature sheep eyes compared to adult sheep eyes. Interestingly, in human eyes, ILM disruption was significantly greater in the posterior pole (p < 0.05) and in people over 60 years of age (p < 0.02). These findings supplement the current discussion surrounding age-related posterior vitreous detachment, and the risk factors and physiological progressions associated with this condition. In addition, these data further our understanding of the biomechanical mechanisms of vitreoretinal adhesion, and can be used to develop age- appropriate computational models simulating retinal detachment, hemorrhaging, or retinal trauma.
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Purpose: We identify long-term ocular sequelae subsequent to experimental blast exposure. Methods: Male Long-Evans rats were exposed to 230 kPa side-on primary blast overpressure using a compressed air driven shock tube. Visual system function and structure were assessed for 8 weeks after exposure using optokinetic nystagmus and optical coherence tomography. Vitreous protein expression and histology (TUNEL, H&E) were performed at 1 day and 1, 4, and 8 weeks. IOP was recorded bilaterally during blast in a subset of animals. Results: Blast pressure profiles resembled the Friedlander waveform indicative of an open field blast. Peak IOP in directly-exposed eyes (240 kPa) was similar to peak blast overpressure, but IOP in indirectly-exposed eyes was 30% lower. Contrast sensitivity of blast-exposed animals decreased significantly by 20% 1 day after blast and did not recover by 8 weeks. Significant swelling and structural damage to the corneal epithelial and stromal layers were observed 2 weeks after blast exposure. Swollen corneas increased 254 ± 143 µm from baseline by 6 weeks, and scarring developed by 8 weeks. Histology revealed additional lens pathology 1 week after blast, suggestive of cataract development. Endothelial cell density increased significantly in blast-exposed animals between 1 and 4 weeks. Neurofilament heavy chain significantly increased after blast and returned to near baseline values by 8 weeks. Inflammatory cytokine changes corroborated ocular pathology findings. Conclusions: These data demonstrate immediate visual dysfunction and biochemical responses, but delayed structural pathology, in response to single primary blast exposure. The delayed pathology time course may provide a window to implement treatment strategies for improved visual outcome.
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Traumatismos por Explosões/etiologia , Catarata/etiologia , Sensibilidades de Contraste/fisiologia , Lesões da Córnea/etiologia , Epitélio Corneano/patologia , Transtornos da Visão/etiologia , Animais , Traumatismos por Explosões/fisiopatologia , Catarata/fisiopatologia , Lesões da Córnea/fisiopatologia , Substância Própria/patologia , Endotélio Corneano/patologia , Proteínas do Olho/metabolismo , Seguimentos , Pressão Intraocular/fisiologia , Masculino , Ratos , Ratos Long-Evans , Tomografia de Coerência Óptica , Transtornos da Visão/fisiopatologia , Corpo Vítreo/metabolismoRESUMO
Purpose: Hyaluronic acid-based polymer films are emerging as drug-delivery vehicles for local and continuous drug administration to the eye. The highly lubricating hyaluronic acid increases comfort, but displaces films from the eye, reducing drug exposure and efficacy. Previous studies have shown that careful control of the surface interaction of the film with the eye is critical for improved retention. Methods: In this study, the frictional interaction of a carboxymethylated, hyaluronic acid-based polymer (CMHA-S) with and without methylcellulose was quantified against ovine and human sclera at three axial loads (0.3, 0.5, and 0.7 N) and four sliding velocities (0.3, 1.0, 10, and 30 mm/s). Results: Static coefficients of friction significantly increased with rate (P < 0.003), ranging between 0.18 ± 0.08 and 0.46 ± 0.13 for 0.3 to 30 mm/s, respectively. Friction became more rate-dependent when methylcellulose was added to CMHA-S. Kinetic coefficient of friction was not affected by rate, and averaged 0.15 ± 0.1. Methylcellulose increased CMHA-S static and kinetic friction by 60% and 80%, respectively, but was also prone to wear during testing. Conclusions: These data suggest that methylcellulose can be used to create a friction differential on the film, but a potentially increased degradation rate with the methylcellulose must be considered in the design.
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Ácido Hialurônico/análogos & derivados , Ácido Hialurônico/química , Polietilenoglicóis/química , Polímeros/química , Esclera/efeitos dos fármacos , Adulto , Animais , Humanos , Lubrificação , Pessoa de Meia-Idade , Modelos Animais , Ovinos , Propriedades de SuperfícieRESUMO
Repetitive back-and-forth head rotation from vigorous shaking is purported to be a central mechanism responsible for diffuse white matter injury, subdural hemorrhage, and retinal hemorrhage in some cases of abusive head trauma (AHT) in young children. Although animal studies have identified mechanisms of traumatic brain injury (TBI) associated with single rapid head acceleration-decelerations at levels experienced in a motor vehicle crash, few experimental studies have investigated TBI from repetitive head rotations. The objective of this study was to systematically investigate the post-injury pathological time-course after cyclic, low-velocity head rotations in the piglet and compare them with single head rotations. Injury metrics were the occurrence and extent of axonal injury (AI), extra-axial hemorrhage (EAH), red cell neuronal/axonal change (RCNAC), and ocular injury (OI). Hyperflexion/extension of the neck were purposefully avoided in the study, resulting in unscaled angular accelerations at the lower end of reported infant surrogate shaking kinematics. All findings were at the mild end of the injury spectrum, with no significant findings at 6 h post-injury. Cyclic head rotations, however, produced modest AI that significantly increased with time post-injury (p < 0.035) and had significantly greater amounts of RCNAC and EAH than noncyclic head rotations after 24 h post-injury (p < 0.05). No OI was observed. Future studies should investigate the contributions of additional physiological and mechanical features associated with AHT (e.g., hyperflexion/extension, increased intracranial pressure from crying or thoracic compression, and more than two cyclic episodes) to enhance our understanding of the causality between proposed mechanistic factors and AHT in infants.
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Lesões Encefálicas/patologia , Traumatismos Craniocerebrais/patologia , Movimentos da Cabeça/fisiologia , Rotação/efeitos adversos , Animais , Animais Recém-Nascidos , Fenômenos Biomecânicos/fisiologia , Lesões Encefálicas/fisiopatologia , Traumatismos Craniocerebrais/fisiopatologia , Feminino , Humanos , Masculino , Síndrome do Bebê Sacudido/patologia , Síndrome do Bebê Sacudido/fisiopatologia , SuínosRESUMO
Clinicians are often faced with the challenging task of distinguishing between accidental and inflicted pediatric head trauma. There is currently a disparity in the anecdotal case study literature as to what kinds of injuries can occur in children from low height falls. There is also a paucity of material property data for pediatric skull and suture at rates similar to those expected in low height falls. We tested human infant (<1 year old) cranial bone and suture from 23 calveria in three-point bending and tension, respectively, at rates ranging from 1.2-2.8 m/sec. Donor age was found to have the largest influence on the elastic modulus and ultimate stress of cranial bone, with an increase in age increasing both material properties. In adults, cranial bone and suture have similar properties and the adult calveria deforms very little prior to fracture. In contrast, pediatric cranial bone is 35 times stiffer than pediatric cranial suture. In addition, pediatric cranial suture deforms 30 times more before failure than pediatric cranial bone and 243 times more than adult cranial bone. The large strains in the pediatric bone and suture result in a skullcase that can undergo dramatic shape changes before fracture, potentially causing substantial deformation in the brain. The sizeable difference between pediatric bone and suture material properties also underscores the crucial role that sutures play in the unique response of the pediatric head to impact in low height falls. These data provide necessary information to enhance our understanding of mechanisms of head injury in young children.
Assuntos
Suturas Cranianas/fisiologia , Crânio/fisiologia , Envelhecimento/fisiologia , Algoritmos , Fenômenos Biofísicos , Biofísica , Osso e Ossos/fisiologia , Elasticidade , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Osso Occipital/fisiologia , Osso Parietal/fisiologia , Reprodutibilidade dos Testes , Crânio/crescimento & desenvolvimento , Estresse MecânicoRESUMO
Computational models of the head can be used to simulate events associated with traumatic brain injury and to design protective equipment and environments. Accurate material property descriptions of biological tissues are crucial to the development of computational models that mimic human responses. Recent finite element models of adult head injury assign distinct homogeneous properties to white and gray matter regions within the brain, based on limited regional data. However, white matter is usually considered homogeneous, despite recent reports of significant mechanical property differences between corpus callosum and corona radiata. In this study, we extend our investigation of homogeneity to gray matter by measuring stiffness of cerebral cortex and comparing it to thalamus from our previous work. Using a parallel plate shear-testing device, we performed a sequence of stress relaxation tests at 2.5%, 5%, 10%, 20%, 30%, 40%, and then 50% strain. Force and displacement were measured and used to determine the stiffness in two different porcine cortical gray matter regions. While no significant difference was found between the two cortical regions, cortical gray matter was significantly less stiff than previously reported values of porcine thalamic gray matter (p<0.01) and human cortical gray matter (p<0.001). These data indicate that while intraregional gray matter may be considered homogenous, there exists heterogeneity between differing regions of the brain. The assumption of gray matter homogeneity should be carefully considered in future finite element models of the head.