RESUMEN
Using high frame-rate ultrasound and ¡1µm sensitive motion tracking we previously showed that shear waves at the surface of ex vivo and in situ brains develop into shear shock waves deep inside the brain, with destructive local accelerations. However post-mortem tissue cannot develop injuries and has different viscoelastodynamic behavior from in vivo tissue. Here we present the ultrasonic measurement of the high-rate shear shock biomechanics in the in vivo porcine brain, and histological assessment of the resulting axonal pathology. A new biomechanical model of brain injury was developed consisting of a perforated mylar surface attached to the brain and vibrated using an electromechanical shaker. Using a custom sequence with 8 interleaved wide beam emissions, brain imaging and motion tracking were performed at 2900 images/s. Shear shock waves were observed for the first time in vivo wherein the shock acceleration was measured to be 2.6 times larger than the surface acceleration ( 95g vs. 36g). Histopathology showed axonal damage in the impacted side of the brain from the brain surface, accompanied by a local shock-front acceleration of >70g. This shows that axonal injury occurs deep in the brain even though the shear excitation was at the brain surface, and the acceleration measurements support the hypothesis that shear shock waves are responsible for deep traumatic brain injuries.
Asunto(s)
Lesiones Encefálicas , Diagnóstico por Imagen de Elasticidad , Animales , Porcinos , Ultrasonografía , Encéfalo/diagnóstico por imagen , Movimiento (Física) , Lesiones Encefálicas/diagnóstico por imagen , Diagnóstico por Imagen de Elasticidad/métodosRESUMEN
Wearable inertial sensors measure human head impact kinematics important to the on-going development and validation of head injury criteria. However, sensor specifications have not been scientifically justified in the context of the anticipated field impact dynamics. The objective of our study is to determine the minimum bandwidth and sample rate required to capture the impact frequency response relevant to injury. We used high-bandwidth head impact data as ground-truth measurements, and investigated the attenuation of various injury criteria at lower bandwidths. Given a 10% attenuation threshold, we determined the minimum bandwidths required to study injury criteria based on skull kinematics and brain deformation in three different model systems: helmeted cadaver (no neck), unhelmeted cadaver (no neck), and helmeted dummy impacts (with neck). We found that higher bandwidths are required for unhelmeted impacts in general and for studying strain rate injury criteria. Minimum gyroscope bandwidths of 300Hz in helmeted sports and 500Hz in unhelmeted sports are necessary to study strain rate based injury criteria. A minimum accelerometer bandwidth of 500Hz in unhelmeted sports is necessary to study most injury criteria. Current devices typically sample at 1000Hz, with gyroscope bandwidths below 200Hz, which are not always sufficient according to these requirements. With hard contact test conditions, the identified requirements may be higher than most soft contacts on the field, but should be satisfied to capture the worst contact, and often higher risk, scenarios relative to the specific sport or activity. Our findings will help establish standard guidelines for sensor choice and design in traumatic brain injury research.
Asunto(s)
Lesiones Traumáticas del Encéfalo/diagnóstico , Acelerometría , Fenómenos Biomecánicos , Lesiones Traumáticas del Encéfalo/patología , Lesiones Traumáticas del Encéfalo/prevención & control , Dispositivos de Protección de la Cabeza , Humanos , Modelos BiológicosRESUMEN
An increasing number of studies have reported blood-brain barrier (BBB) dysfunction after blast-induced traumatic brain injury (bTBI). Despite this evidence, there is limited quantitative understanding of the extent of BBB opening and the time course of damage after blast injury. In addition, many studies do not report kinematic parameters of head motion, making it difficult to separate contributions of primary and tertiary blast-loading. Detailed characterization of blast-induced BBB damage may hold important implications for serum constituents that may potentially cross the compromised barrier and contribute to neurotoxicity, neuroinflammation, and persistent neurologic deficits. Using an in vivo bTBI model, systemic administration of sodium fluorescein (NaFl; 376 Da), Evans blue (EB; 69 kDa when bound to serum albumin), and dextrans (3-500 kDa) was used to estimate the pore size of BBB opening and the time required for recovery. Exposure to blast with 272 ± 6 kPa peak overpressure, 0.69 ± 0.01 ms duration, and 65 ± 1 kPa*ms impulse resulted in significant acute extravasation of NaFl, 3 kDa dextran, and EB. However, there was no significant acute extravasation of 70 kDa or 500 kDa dextrans, and minimal to no extravasation of NaFl, dextrans, or EB 1 day after exposure. This study presents a detailed analysis of the time course and pore size of BBB opening after bTBI, supported by a characterization of kinematic parameters associated with blast-induced head motion.
Asunto(s)
Traumatismos por Explosión/complicaciones , Barrera Hematoencefálica/lesiones , Barrera Hematoencefálica/fisiopatología , Lesiones Traumáticas del Encéfalo/complicaciones , Modelos Animales de Enfermedad , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Up to 80% of injuries sustained by U.S. soldiers in Operation Enduring Freedom and Operation Iraqi Freedom were the result of blast exposure from improvised explosive devices. Some soldiers experience multiple blasts while on duty, and it has been suggested that symptoms of repetitive blast are similar to those that follow multiple non-blast concussions, such as sport-related concussion. Despite the interest in the effects of repetitive blast exposure, it remains unknown whether an initial blast renders the brain more vulnerable to subsequent exposure, resulting in a synergistic injury response. To investigate the effect of multiple primary blasts on the brain, organotypic hippocampal slice cultures were exposed to single or repetitive (two or three total) primary blasts of varying intensities. Long-term potentiation was significantly reduced following two Level 2 (92.7 kPa, 1.4 msec, 38.5 kPa·msec) blasts delivered 24 h apart without altering basal evoked response. This deficit persisted when the interval between injuries was increased to 72 h but not when the interval was extended to 144 h. The repeated blast exposure with a 24 h interval increased microglia staining and activation significantly but did not significantly increase cell death or damage axons, dendrites, or principal cell layers. Lack of overt structural damage and change in basal stimulated neuron response suggest that injury from repetitive primary blast exposure may specifically affect long-term potentiation. Our studies suggest repetitive primary blasts can exacerbate injury dependent on the injury severity and interval between exposures.
Asunto(s)
Traumatismos por Explosión/fisiopatología , Hipocampo/fisiopatología , Potenciación a Largo Plazo/fisiología , Animales , Técnicas de Cultivo de Órganos , Ratas , Ratas Sprague-DawleyRESUMEN
Head injury is a persistent and costly problem for both children and adults. Globally, approximately 10 million people are hospitalized each year for head injuries. Knowing the structural properties of the head is important for modeling the response of the head in impact, and for providing insights into mechanisms of head injury. Hence, the goal of this study was to measure the sub-injurious structural stiffness of whole pediatric heads. 12 cadaveric pediatric (20-week-gestation to 16 years old) heads were tested in a battery of viscoelastic compression tests. The heads were compressed in both the lateral and anterior-posterior directions to 5% of gauge length at normalized deformation rates of 0.0005/s, 0.01/s, 0.1/s, and 0.3/s. Because of the non-linear nature of the response, linear regression models were used to calculate toe region (<2.5%) and elastic region (>2.5%) stiffness separately so that meaningful comparisons could be made across rate, age, and direction. The results showed that age was the dominant factor in predicting the structural stiffness of the human head. A large and statistically significant increase in the stiffness of both the toe region and the elastic region was observed with increasing age (p<0.0001), but no significant difference was seen across direction or normalized deformation rate. The stiffness of the elastic region increased from as low as 5 N/mm in the neonate to >4500 N/mm in the 16 year old. The changes in stiffness with age may be attributed to the disappearance of soft sutures and the thickening of skull bones with age.
Asunto(s)
Fuerza Compresiva , Traumatismos Craneocerebrales/fisiopatología , Cráneo/ultraestructura , Adolescente , Cadáver , Niño , Preescolar , Femenino , Cabeza , Humanos , Lactante , Modelos Lineales , MasculinoRESUMEN
Owing to the frequent incidence of blast-induced traumatic brain injury (bTBI) in recent military conflicts, there is an urgent need to develop effective therapies for bTBI-related pathologies. Blood-brain barrier (BBB) breakdown has been reported to occur after primary blast exposure, making restoration of BBB function and integrity a promising therapeutic target. We tested the hypothesis that treatment with dexamethasone (DEX) after primary blast injury potentiates recovery of an in vitro BBB model consisting of mouse brain endothelial cells (bEnd.3). DEX treatment resulted in complete recovery of transendothelial electrical resistance and hydraulic conductivity 1 day after injury, compared with 3 days for vehicle-treated injured cultures. Administration of RU486 (mifepristone) inhibited effects of DEX, confirming that barrier restoration was mediated by glucocorticoid receptor signaling. Potentiated recovery with DEX treatment was accompanied by stronger zonula occludens (ZO)-1 tight junction immunostaining and expression, suggesting that increased ZO-1 expression was a structural correlate to BBB recovery after blast. Interestingly, augmented ZO-1 protein expression was associated with specific upregulation of the α(+) isoform but not the α(-) isoform. This is the first study to provide a mechanistic basis for potentiated functional recovery of an in vitro BBB model because of glucocorticoid treatment after primary blast injury.
Asunto(s)
Traumatismos por Explosión/tratamiento farmacológico , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/fisiopatología , Dexametasona/uso terapéutico , Glucocorticoides/uso terapéutico , Proteína de la Zonula Occludens-1/metabolismo , Animales , Traumatismos por Explosión/metabolismo , Traumatismos por Explosión/fisiopatología , Barrera Hematoencefálica/metabolismo , Línea Celular , Ratones , Proteína de la Zonula Occludens-1/análisisRESUMEN
The morphological and mechanical properties of the pediatric skull are important in understanding pediatric head injury biomechanics. Although previous studies have analyzed the morphology of cranial sutures, none has done so in pediatric specimens nor have previous studies related the morphology to mechanical properties of human sutures. This study quantified the geometry of pediatric cranial sutures and investigated its correlation with the suture mechanical properties. First, the suture fiber alignment was quantified using histological analysis for four ages-neonate, 9 months-old, 11 months-old, and 18 months-old. For the morphometric investigation of the suture interdigitation, suture samples from a 6-year-old were scanned using micro-CT and the level of interdigitation was measured using two techniques. The first technique, the sinuosity index, was calculated by dividing the suture path along the surface of the skull by the suture distance from beginning to end. The second technique, the surface area interdigitation index, was calculated by measuring the surface area of the bone interface outlining the suture and dividing it by the cross-sectional area of the bone. The mechanical properties were obtained using methods reported in Davis et al.6. The results of the histological analysis showed a significant increase in fiber alignment in older specimen; where random fiber alignment has an average angle deviation of 45°, neonatal suture fibers have an average deviation of 32.2° and the 18-month-old fibers had an average deviation of 16.2° (p < 0.0001). For the suture index measurements, only the sinuosity was positively correlated with the ultimate strain (R (2) = 0.62, Bonferroni corrected p = 0.011) but no other measurements showed a significant relationship, including the amount of interdigitation and elastic modulus. Our results demonstrate that there is a distinct developmental progression of the suture fiber alignment at a young age, but the differences in suture interdigitation can only predict the ultimate strain and no other mechanical properties.
Asunto(s)
Suturas Craneales/diagnóstico por imagen , Traumatismos Craneocerebrales/diagnóstico por imagen , Microtomografía por Rayos X , Niño , Suturas Craneales/fisiopatología , Traumatismos Craneocerebrales/fisiopatología , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
Modern ballistic helmets defeat penetrating bullets by energy transfer from the projectile to the helmet, producing helmet deformation. This deformation may cause severe injuries without completely perforating the helmet, termed "behind armor blunt trauma" (BABT). As helmets become lighter, the likelihood of larger helmet backface deformation under ballistic impact increases. To characterize the potential for BABT, seven postmortem human head/neck specimens wearing a ballistic protective helmet were exposed to nonperforating impact, using a 9 mm, full metal jacket, 124 grain bullet with velocities of 400-460 m/s. An increasing trend of injury severity was observed, ranging from simple linear fractures to combinations of linear and depressed fractures. Overall, the ability to identify skull fractures resulting from BABT can be used in forensic investigations. Our results demonstrate a high risk of skull fracture due to BABT and necessitate the prevention of BABT as a design factor in future generations of protective gear.
Asunto(s)
Dispositivos de Protección de la Cabeza , Fractura Craneal Deprimida/diagnóstico por imagen , Fractura Craneal Deprimida/patología , Fracturas Craneales/diagnóstico por imagen , Fracturas Craneales/patología , Heridas por Arma de Fuego/patología , Anciano , Anciano de 80 o más Años , Fenómenos Biomecánicos , Cadáver , Contusiones/patología , Diseño de Equipo , Balística Forense , Patologia Forense , Humanos , Masculino , Persona de Mediana Edad , RadiografíaRESUMEN
Recent studies have demonstrated increased susceptibility to breakdown of the cerebral vasculature associated with repetitive traumatic brain injury. We hypothesized that exposure to two consecutive blast injuries would result in exacerbated damage to an in vitro model of the blood-brain barrier (BBB) compared with exposure to a single blast of the same severity. Contrary to our hypothesis, however, repeated mild or moderate primary blast delivered with a 24 or 72 h interval between injuries did not significantly exacerbate reductions in transendothelial electrical resistance (TEER) across a brain endothelial monolayer compared with sister cultures receiving a single exposure of the same intensity. Permeability of the barrier to a range of different-sized solutes remained unaltered after single and repeated blast, supporting that the effects of repeated blast on BBB integrity were not additive. Single blast exposure significantly reduced immunostaining of ZO-1 and claudin-5 tight junction proteins, but subsequent exposure did not cause additional damage to tight junctions. Although repeated blast did not further reduce TEER, the second exposure delayed TEER recovery in BBB cultures. Similarly, recovery of hydraulic conductivity through the BBB was delayed by a second exposure. Extending the interinjury interval to 72 h, the effects of multiple injuries on the BBB were found to be independent given sufficient recovery time between consecutive exposures. Careful investigation of the effects of repeated blast on the BBB will help identify injury levels and a temporal window of vulnerability associated with BBB dysfunction, ultimately leading to improved strategies for protecting warfighters against repeated blast-induced disruption of the cerebral vasculature.