Cameron Dale Bass

The Mechanics of Traumatic Brain Injury: A Review of What We Know and What We Need to Know for Reducing Its Societal Burden

Traumatic brain injury (TBI) is a significant public health problem, on pace to become the third leading cause of death worldwide by 2020. Moreover, emerging evidence linking repeated mild traumatic brain injury to long-term neurodegenerative disorders points out that TBI can be both an acute disorder and a chronic disease. We are at an important transition point in our understanding of TBI, as past work has generated significant advances in better protecting us against some forms of moderate and severe TBI. However, we still lack a clear understanding of how to study milder forms of injury, such as concussion, or new forms of TBI that can occur from primary blast loading. In this review, we highlight the major advances made in understanding the biomechanical basis of TBI. We point out opportunities to generate significant new advances in our understanding of TBI biomechanics, especially as it appears across the molecular, cellular, and whole organ scale.

Blood-Brain Barrier Dysfunction after Primary Blast Injury in vitro

The incidence of blast-induced traumatic brain injury (bTBI) has increased substantially in recent military conflicts. However, the consequences of bTBI on the blood-brain barrier (BBB), a specialized cerebrovascular structure essential for brain homeostasis, remain unknown. In this study, we utilized a shock tube driven by compressed gas to generate operationally relevant, ideal pressure profiles consistent with improvised explosive devices (IEDs). By multiple measures, the barrier function of an in vitro BBB model was disrupted following exposure to a range of controlled blast loading conditions. Trans-endothelial electrical resistance (TEER) decreased acutely in a dose-dependent manner that was most strongly correlated with impulse, as opposed to peak overpressure or duration. Significantly increased hydraulic conductivity and solute permeability post-injury further confirmed acute alterations in barrier function. Compromised ZO-1 immunostaining identified a structural basis for BBB breakdown. After blast exposure, TEER remained significantly depressed 2 days post-injury, followed by spontaneous recovery to pre-injury control levels at day 3. This study is the first to report immediate disruption of an in vitro BBB model following primary blast exposure, which may be important for the development of novel helmet designs to help mitigate the effects of blast on the BBB.

Isolated Primary Blast Alters Neuronal Function with Minimal Cell Death in Organotypic Hippocampal Slice Cultures

An increasing number of U.S. soldiers are diagnosed with traumatic brain injury (TBI) subsequent to exposure to blast. In the field, blast injury biomechanics are highly complex and multi-phasic. The pathobiology caused by exposure to some of these phases in isolation, such as penetrating or inertially driven injuries, has been investigated extensively. However, it is unclear whether the primary component of blast, a shock wave, is capable of causing pathology on its own. Previous in vivo studies in the rodent and pig have demonstrated that it is difficult to deliver a primary blast (i.e., shock wave only) without rapid head accelerations and potentially confounding effects of inertially driven TBI. We have previously developed a well-characterized shock tube and custom in vitro receiver for exposing organotypic hippocampal slice cultures to pure primary blast. In this study, isolated primary blast induced minimal hippocampal cell death (on average, below 14% in any region of interest), even for the most severe blasts tested (424 kPa peak pressure, 2.3 ms overpressure duration, and 248 kPa*ms impulse). In contrast, measures of neuronal function were significantly altered at much lower exposures (336 kPa, 0.84 ms, and 86.5 kPa*ms), indicating that functional changes occur at exposures below the threshold for cell death. This is the first study to investigate a tolerance for primary blast-induced brain cell death in response to a range of blast parameters and demonstrate functional deficits at subthreshold exposures for cell death.

Repeated primary blast injury causes delayed recovery, but not additive disruption, in an in vitro blood-brain barrier model.

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.

The mechanical and morphological properties of 6 year-old cranial bone

Traumatic Brain Injury (TBI) is a leading cause of mortality and morbidity for children in the United States. The unavailability of pediatric cadavers makes it difficult to study and characterize the mechanical behavior of the pediatric skull. Computer based finite element modeling could provide valuable insights, but the utility of these models depends upon the accuracy of cranial material property inputs. In this study, 47 samples from one six year-old human cranium were tested to failure via four point bending to study the effects of strain rate and the structure of skull bone on modulus of elasticity and failure properties for both cranial bone and suture. The results show that strain rate does not have a statistically meaningful effect on the mechanical properties of the six year-old skull over the range of strain rates studied (average low rate of 0.045 s(-1), average medium rate of 0.44 s(-1), and an average high rate of 2.2 s(-1)), but that these properties do depend on the growth patterns and morphology of the skull. The thickness of the bone was found to vary with structure. The bending stiffness (per unit width) for tri-layer bone (12.32±5.18 Nm(2)/m) was significantly higher than that of cortical bone and sutures (5.58±1.46 Nm(2)/m and 3.70±1.88 Nm(2)/m respectively). The modulus of elasticity was 9.87±1.24 GPa for cranial cortical bone and 1.10±0.53 GPa for sutures. The effective elastic modulus of tri-layer bone was 3.69±0.92 GPa. Accurate models of the pediatric skull should account for the differences amongst these three distinct tissues in the six year-old skull.

The response of the adult and ATD heads to impacts onto a rigid surface

Given the high incidence of TBI, head injury has been studied extensively using both cadavers and anthropomorphic test devices (ATDs). However, few studies have benchmarked the response of ATD heads against human data. Hence, the objective of this study is to investigate the response of adult and ATD heads in impact, and to compare adult Hybrid III head responses to the adult head responses. In this study, six adult human heads and seven ATD heads were used to obtain impact properties. The heads were dropped from both 15cm and 30cm onto five impact locations: right and left parietal, forehead, occiput and vertex. One set of drops were performed on the human heads and up to four sets were carried out on the ATD heads. For each drop, the head was placed into a fine net and positioned to achieve the desired drop height and impact location. The head was then released to allow free fall without rotation onto a flat aluminum 34 -inch thick platen. The platen was attached to a three-axis piezoelectric load cell to measure the impact force. The peak resultant acceleration, head impact criterion (HIC) and impact stiffness were calculated using the force/time curve and drop mass. No statistical differences were found between the adult human heads and the adult Hybrid III head for 15cm and 30cm impacts (p>0.05). For the human heads, the mid-sagittal impact locations produced the highest HIC and peak acceleration values. The parietal impacts produced HICs and peak accelerations that were 26-48% lower than those from the mid-sagittal impacts. For the ATD heads, the acceleration and HIC values generally increased with represented age, except for the Q3, which produced HIC values up to higher than the other ATD heads. The impact responses of the adult Hybrid III onto different impact locations were found to adequately represent the impact stiffness of human adult head impacts from 30cm and below onto a rigid surface. The Q3 dummy consistently produced the highest HIC values of the ATD heads, and produced higher acceleration and HIC values than the adult human heads as well, which is contrary to neonatal data demonstrating that the head acceleration increases with age.

Experimental Modal Analysis of the Advanced Combat Helmet

In this work we present a study of the characterization of an Advanced Combat Helmet (ACH) using experimental modal analysis techniques. A medium-sized helmet was impacted at different location and the vibration response was used to estimate a global frequency model. This was achieved using the modal parameters of the local models obtained for a specific input-output location and combining them in a global model. The estimation of the frequency model was done using well-established least squares techniques, while the contribution of measurement noise in input and output was considered.Copyright