William C. Moss

Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model

Blast exposure is associated with chronic traumatic encephalopathy, impaired neuronal function, and persistent cognitive deficits in blast-exposed military veterans and experimental animals. Blast Brain: An Invisible Injury Revealed Traumatic brain injury (TBI) is the “signature” injury of the conflicts in Afghanistan and Iraq and is associated with psychiatric symptoms and long-term cognitive disability. Recent estimates indicate that TBI may affect 20% of the 2.3 million U.S. servicemen and women deployed since 2001. Chronic traumatic encephalopathy (CTE), a tau protein–linked neurodegenerative disorder reported in athletes with multiple concussions, shares clinical features with TBI in military personnel exposed to explosive blast. However, the connection between TBI and CTE has not been explored in depth. In a new study, Goldstein et al. investigate this connection in the first case series of postmortem brains from U.S. military veterans with blast exposure and/or concussive injury. They report evidence for CTE neuropathology in the military veteran brains that is similar to that observed in the brains of young amateur American football players and a professional wrestler. The investigators developed a mouse model of blast neurotrauma that mimics typical blast conditions associated with military blast injury and discovered that blast-exposed mice also demonstrate CTE neuropathology, including tau protein hyperphosphorylation, myelinated axonopathy, microvascular damage, chronic neuroinflammation, and neurodegeneration. Surprisingly, blast-exposed mice developed CTE neuropathology within 2 weeks after exposure to a single blast. In addition, the neuropathology was accompanied by functional deficits, including slowed axonal conduction, reduced activity-dependent long-term synaptic plasticity, and impaired spatial learning and memory that persisted for 1 month after exposure to a single blast. The investigators then showed that blast winds with velocities of more than 330 miles/hour—greater than the most intense wind gust ever recorded on earth—induced oscillating head acceleration of sufficient intensity to injure the brain. The researchers then demonstrated that blast-induced learning and memory deficits in the mice were reduced by immobilizing the head during blast exposure. These findings provide a direct connection between blast TBI and CTE and indicate a primary role for blast wind–induced head acceleration in blast-related neurotrauma and its aftermath. This study also validates a new blast neurotrauma mouse model that will be useful for developing new diagnostics, therapeutics, and rehabilitative strategies for treating blast-related TBI and CTE. Blast exposure is associated with traumatic brain injury (TBI), neuropsychiatric symptoms, and long-term cognitive disability. We examined a case series of postmortem brains from U.S. military veterans exposed to blast and/or concussive injury. We found evidence of chronic traumatic encephalopathy (CTE), a tau protein–linked neurodegenerative disease, that was similar to the CTE neuropathology observed in young amateur American football players and a professional wrestler with histories of concussive injuries. We developed a blast neurotrauma mouse model that recapitulated CTE-linked neuropathology in wild-type C57BL/6 mice 2 weeks after exposure to a single blast. Blast-exposed mice demonstrated phosphorylated tauopathy, myelinated axonopathy, microvasculopathy, chronic neuroinflammation, and neurodegeneration in the absence of macroscopic tissue damage or hemorrhage. Blast exposure induced persistent hippocampal-dependent learning and memory deficits that persisted for at least 1 month and correlated with impaired axonal conduction and defective activity-dependent long-term potentiation of synaptic transmission. Intracerebral pressure recordings demonstrated that shock waves traversed the mouse brain with minimal change and without thoracic contributions. Kinematic analysis revealed blast-induced head oscillation at accelerations sufficient to cause brain injury. Head immobilization during blast exposure prevented blast-induced learning and memory deficits. The contribution of blast wind to injurious head acceleration may be a primary injury mechanism leading to blast-related TBI and CTE. These results identify common pathogenic determinants leading to CTE in blast-exposed military veterans and head-injured athletes and additionally provide mechanistic evidence linking blast exposure to persistent impairments in neurophysiological function, learning, and memory.

Telomerized human microvasculature is functional in vivo.

Previously we showed the superior in vitro survival of human telomerase reverse transcriptase (hTERT)-transduced human endothelial cells (EC). Here we show that retroviral-mediated transduction of hTERT in human dermal microvascular EC (HDMEC) results in cell lines that form microvascular structures when subcutaneously implanted in severe combined immunodeficiency (SCID) mice. Anti-human type IV collagen basement membrane immunoreactivity and visualization of enhanced green fluorescent protein (eGFP)-labeled microvessels confirmed the human origin of these capillaries. No human vasculature was observed after implantation of HT1080 fibrosarcoma cells, 293 human embryonic kidney cells, or human skin fibroblasts. Intravascular red fluorescent microspheres injected into host circulation were found within green “telomerized” microvessels, indicating functional murine–human vessel anastamoses. Whereas primary HDMEC-derived vessel density decreased with time, telomerized HDMEC maintained durable vessels six weeks after xenografting. Modulation of implant vessel density by exposure to different angiogenic and angiostatic factors demonstrated the utility of this system for the study of human microvascular remodeling in vivo.

Finite element analysis of the diamond anvil cell: Achieving 4.6 Mbar

We have performed a comprehensive finite element analysis of the diamond anvil cell. Our analysis shows how beveled diamonds and material properties of the gasket affect diamond anvil cell performance. Using the results of the analysis, we have achieved 4.6 Mbar experimentally, which is the highest static pressure reported to date. Possible methods to increase the pressure further are discussed.

Sonoluminescence and the prospects for table-top micro-thermonuclear fusion

Abstract Hydrodynamic simulations of a collapsing bubble show that pure D2 cannot exhibit picosecond sonoluminescence, because of its large sound speed. The addition of D2O vapor lowers the sound speed and produces calculated results consistent with experiments. A pressure spike added to the periodic driving amplitude creates temperatures that may be sufficient to generate a very small number of thermonuclear D-D fusion reactions in the bubble.

The acoustic emissions from single-bubble sonoluminescence

Detailed measurements of the acoustic emissions from single-bubble sonoluminescence have been made utilizing both a small 200-μm aperture PVDF needle hydrophone, and a focused 10-MHz transducer. Signals obtained with the needle hydrophone show a fast (5.2 ns), probably bandlimited rise time and relatively large pulse amplitude (≈1.7 bar). Below the sonoluminescence threshold, the emissions are observable, but considerably smaller in amplitude (≈0.4 bar). Several signals are observed with the 10-MHz transducer and correspond to acoustic emissions from the bubble during the main collapse, as well as from the rebounds. Experiments reveal that the acoustic emissions occur at or near the minimum bubble radius. Calculations of the peak pressures and pulse widths are compared with experimental data.

On instabilities in large deformation simple shear loading

Abstract We obtain finite strain solutions for an elastic-perfectly-plastic isotropic material under simple shear loading. The effects of using the Jaumann, Green-Naghdi, and Truesdell stress rates are examined. An analytic solution is obtained using the Jaumann rate, and numerical solutions are obtained for the Green-Naghdi and Truesdell rates. The shear stress, as a function of the shear strain is nonmonotonic, and consequently ‘unstable’, for all three stress rates, which is contrary to previously published results.

Finite element design of diamond anvils

We have performed finite element analyses of beveled diamond anvils. Our analyses show that double beveling can improve the performance of the diamond anvil cell and maintain the stability of the sample, which is often sacrificed when large angle single bevel diamonds are used.

A new damping mechanism in strongly collapsing bubbles

A gas‐filled bubble in a liquid undergoes cycles of growth, rapid collapse, and damped rebounds in response to a driving pressure. These nonlinear oscillations can be simulated using the Rayleigh‐Plesset equation (RPE), which was developed 50 years ago and is the foundation for almost all theoretical analyses of nonlinear bubble dynamics. A major deficiency of the RPE is that for strongly driven bubbles, such as sonoluminescing bubbles, it produces large‐amplitude rebounds that often last until the next acoustic cycle of the periodic driving pressure. This is in contrast to the data, which show rapidly damped rebounds. Every derivation of the RPE assumes that the compressibility of the liquid gives rise to the damping. It is shown here that appreciable damping also comes from the most compressible part of the system, which is the gas; specifically, the damping arises from the inhomogeneous pressure field within a rapidly collapsing or expanding bubble. This simple physical reasoning generates a new modification of the RPE that better reproduces the extreme damping that is observed experimentally; a result that cannot be obtained with any other version of the RPE. Our results affect theoretical predictions of the limits of stability of sonoluminescing bubbles as well as theoretical predictions of the magnitude of acoustic emissions from collapsing bubbles.

Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model

The mechanisms underpinning concussion, traumatic brain injury (TBI) and chronic traumatic encephalopathy (CTE) are poorly understood. Using neuropathological analyses of brains from teenage athletes, a new mouse model of concussive impact injury, and computational simulations, Tagge et al. show that head injuries can induce TBI and early CTE pathologies independent of concussion.

Understanding the periodic driving pressure in the Rayleigh–Plesset equation.

The radial motion of a single bubble in a periodically driven liquid is simulated by solving the Rayleigh–Plesset equation and the fully compressible hydrodynamic equations. The hydrodynamic equations require a much smaller far‐field periodic driving pressure than the Rayleigh‐Plesset equations to produce the same maximum bubble radius. The discrepancy is resolved by constructing analytic traveling and standing wave solutions that show the relationship between the far‐field periodic driving pressure and the pressure near the bubble, which is actually responsible for the radial motion. [This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract No. W‐7405‐Eng‐48.]