An Approach for Studying the Direct Effects of Shock Waves on Neuronal Cell Structure and Function

Recent U.S. military conflicts have underscored the knowledge gap regarding the neurological changes associated with blast-induced traumatic brain injury (bTBI). In vitro models of TBIs have the advantage of following the neuronal response to biomechanical perturbations in real-time, which can be exceedingly difficult in animal models. Here, we sought to develop an in vitro approach with controlled blast biomechanics to study the direct effects of the primary shock wave at the neuronal level. A blast injury apparatus mimicking the human skull and cerebrospinal fluid was developed. Primary neuronal cells were cultured inside the apparatus and exposed to a 70 kPa peak blast overpressure using helium gas in a blast tube. Neuronal viability was measured 24 h after blast exposure. The transmission of the pressure wave through the skull is believed to be a factor in injury to the cells of the brain. Three thicknesses in the apparatus wall were studied to represent the range of thicknesses in a human skull. To study the transmission of the shock wave to the neurons, the incident pressure at the apparatus location, as well as internal apparatus pressure, were measured. Analysis of the internal pressure wave revealed that wave oscillation frequency, not amplitude, was a significant factor in cell viability after a bTBI. This finding is related to the viscoelastic properties of the brain and suggests that the transmission of the shock wave through the skull is an important variable in blast injury.