A 3-D Rat Brain Model for Blast-Wave Exposure: Effects of Brain Vasculature and Material Properties.

Exposure to blast waves is suspected to cause primary traumatic brain injury. However, existing finite-element (FE) models of the rat head lack the necessary fidelity to characterize the biomechanical responses in the brain due to blast exposure. They neglect to represent the cerebral vasculature, which increases brain stiffness, and lack the appropriate brain material properties characteristic of high strain rates observed in blast exposures. To address these limitations, we developed a high-fidelity three-dimensional FE model of a rat head. We explicitly represented the rat's cerebral vasculature and used high-strain-rate material properties of the rat brain. For a range of blast overpressures (100 to 230 kPa) the brain-pressure predictions matched experimental results and largely overlapped with and tracked the incident pressure-time profile. Incorporating the vasculature decreased the average peak strain in the cerebrum, cerebellum, and brainstem by 17, 33, and 18%, respectively. When compared with our model based on rat-brain properties, the use of human-brain properties in the FE model led to a three-fold reduction in the strain predictions. For simulations of blast exposure in rats, our findings suggest that representing cerebral vasculature and species-specific brain properties has a considerable influence in the resulting brain strain but not the pressure predictions.

Cerebrovascular dysfunction following subfailure axial stretch.

Cerebral blood vessels are vital to maintaining the health of the brain. Traumatic brain injury (TBI) commonly results in autoregulatory dysfunction and associated failure of cerebral vessels to maintain homeostasis in the brain. While post-injury changes to brain biochemistry are known to contribute to this dysfunction, tissue deformation may also directly alter vascular smooth muscle cell (SMC) function. As a first step toward understanding stretch-induced dysfunction, this study investigates the effect of overstretch on the contractile behavior of SMCs in middle cerebral arteries (MCAs). We hypothesized that vessel function is altered above a threshold of stretch and strain rate. Twenty-four MCAs from Sprague Dawley rats were tested. Following development of basal SMC tone, vessels were subjected to increasing levels of isosmotic extracellular potassium (K+). Samples were then subjected to an axial overstretch of either 1.2*λIV or 1.3*λIV at strain rates of 0.2 or 20s-1. Following overstretch, SMC contractile behavior was measured again, both immediately and 60min after overstretch. Control vessels were subjected to the same protocol but without overstretch. SMC contractile behavior was characterized using both percent contraction (%C) relative to the fully dilated inner diameter and the K+ dose required to evoke the half maximal contractile response (EC50). Control vessels exhibited increased sensitivity to K+ in successive characterization tests, so all effects were quantified relative to the time-matched control response. Samples exhibited the typical biphasic response to extracellular K+, dilating and contracting in response to small and large K+ concentrations, respectively. As hypothesized, axial overstretch altered SMC contractile behavior, as seen in a decrease in %C for sub-maximal contractile K+ doses (p<0.05) and an increase in EC50 (p<0.01), but only for the test group stretched rapidly to 1.3*λIV. While the change in %C was only significantly different immediately after overstretch, the change to EC50 persisted for 60min. These results indicate that deformation can alter SMC contractile behavior and thus potentially play a role in cerebrovascular autoregulatory dysfunction independent of the pathological chemical environment in the brain post-TBI.

Subfailure overstretch induces persistent changes in the passive mechanical response of cerebral arteries.

Cerebral blood vessels are critical in maintaining the health of the brain, but their function can be disrupted by traumatic brain injury (TBI). Even in cases without hemorrhage, vessels are deformed with the surrounding brain tissue. This subfailure deformation could result in altered mechanical behavior. This study investigates the effect of overstretch on the passive behavior of isolated middle cerebral arteries (MCAs), with the hypothesis that axial stretch beyond the in vivo length alters this response. Twenty nine MCA sections from 11 ewes were tested. Vessels were subjected to a baseline test consisting of an axial stretch from a buckled state to 1.05* in vivo stretch (λIV) while pressurized at 13.3 kPa. Specimens were then subjected to a target level of axial overstretch between 1.05*λIV (λz = 1.15) and 1.52*λIV (λz = 1.63). Following overstretch, baseline tests were repeated immediately and then every 10 min, for 60 min, to investigate viscoelastic recovery. Injury was defined as an unrecoverable change in the passive mechanical response following overstretch. Finally, pressurized MCAs were pulled axially to failure. Post-overstretch response exhibited softening such that stress values at a given level of stretch were lower after injury. The observed softening also generally resulted in increased non-linearity of the stress-stretch curve, with toe region slope decreasing and large deformation slope increasing. There was no detectable change in reference configuration or failure values. As hypothesized, the magnitude of these alterations increased with overstretch severity, but only once overstretch exceeded 1.2*λIV (p < 0.001). These changes were persistent over 60 min. These changes may have significant implications in repeated TBI events and in increased susceptibility to stroke post-TBI.

Distribution of blood-brain barrier disruption in primary blast injury.

Traumatic brain injury (TBI) resulting from explosive-related blast overpressure is a topic at the forefront of neurotrauma research. Compromise of the blood-brain barrier (BBB) and other cerebral blood vessel dysfunction is commonly reported in both experimental and clinical studies on blast injury. This study used a rifle primer-driven shock tube to investigate cerebrovascular injury in rats exposed to low-impulse, pure primary blast at three levels of overpressure (145, 232, and 323 kPa) and with three survival times (acute, 24, and 48 h). BBB disruption was quantified immunohistochemically by measuring immunoglobulin G (IgG) extravasation with image analysis techniques. Pure primary blast generated small lesions scattered throughout the brain. The number and size of lesions increased with peak overpressure level, but no significant difference was seen between survival times. Despite laterally directed blast exposure, equal numbers of lesions were found in each hemisphere of the brain. These observations suggest that cerebrovascular injury due to primary blast is distinct from that associated with conventional TBI.

Biaxial and failure properties of passive rat middle cerebral arteries.

Rodents are commonly used as test subjects in research on traumatic brain injury and stroke. However, study of rat cerebral vessel properties has largely been limited to pressure-diameter response within the physiological loading range. A more complete, multiaxial description is needed to guide experiments on rats and rat vessels and to appropriately translate findings to humans. Accordingly, we dissected twelve rat middle cerebral arteries (MCAs) and subjected them to combined inflation and axial stretch tests around physiological loading conditions while in a passive state. The MCAs were finally stretched axially to failure. Results showed that MCAs under physiological conditions were stiffer in the axial than circumferential direction by a mean (±standard deviation) factor of 1.72 (±0.73), similar to previously reported behavior of human cerebral arteries. However, the stiffness for both directions was lower in rat MCA than in human cerebral arteries (p<0.01). Failure stretch values were higher in rat MCA (1.35±0.08) than in human vessels (1.24±0.09) (p=0.003), but corresponding 1st Piola Kirchhoff stress values for rats (0.42±0.09 MPa) were considerably lower than those for humans (3.29±0.64 MPa) (p<0.001). These differences between human and rat vessel properties should be considered in rat models of human cerebrovascular injury and disease.

Timing of tensor and levator veli palatini force application determines eustachian tube resistance patterns during the forced-response test.

OBJECTIVES: The forced-response test (FRT) is used to assess eustachian tube (ET) function in patients with middle ear disease (otitis media). This test often documents a dynamic pattern of luminal dilation and constriction during swallowing which can be quantified as a function relating active tubal resistance with time. The goal of this study is to use a generalized finite element model (FEM) to test the hypothesis that the relative timing of muscle force application by the tensor veli palatini muscle (mTVP) and levator veli palatini muscle (mLVP) on the ET determines the form of active resistance functions. METHODS: Seven resistance waveforms were obtained during the FRT in five adult subjects. A 2D FEM of the ET was constructed from an adult histological specimen and viscoelastic tissue mechanical properties were specified based on measurements obtained in each subject. Least-squared regression routines were used to vary the timing and magnitude of mTVP and mLVP force applications to the ET in order to match the active resistance functions recorded during the FRT. RESULTS: Variation of muscle force timing and magnitude in the FEM simulations reproduced the seven active resistance waveforms with high fidelity. Early application of mTVP force in combination with mLVP force produced a waveform characterized by an initial dilation (low resistances) followed by lumen constriction (higher resistances), while delayed mTVP force application caused an initial lumen constriction followed by dilation. CONCLUSIONS: These results indicate that the active resistance waveforms observed during the FRT reflect differences in the temporal pattern of mLVP and mTVP force application to the ET and emphasize that, like the mTVP, the mLVP functionally interacts with the ET. Results also indicate that in normal adults contraction of the mLVP promotes lumen constriction and that the initial lumen constriction is highly sensitive to the relative delay timing of mTVP and mLVP force application.