TY - JOUR PY - 2012// TI - A Multiscale Approach to Blast Neurotrauma Modeling: Part II: Methodology for Inducing Blast Injury to in vitro Models JO - Frontiers in neurology A1 - Effgen, Gwen Brink A1 - Hue, Christopher Donald A1 - Vogel, Edward A1 - Panzer, Matthew B. A1 - Meaney, David F. A1 - Bass, Cameron R. A1 - Morrison, Barclay SP - 23 EP - 23 VL - 3 IS - N2 - Due to the prominent role of improvised explosive devices (IEDs) in wounding patterns of U.S. war-fighters in Iraq and Afghanistan, blast injury has risen to a new level of importance and is recognized to be a major cause of injuries to the brain. However, an injury risk-function for microscopic, macroscopic, behavioral, and neurological deficits has yet to be defined. While operational blast injuries can be very complex and thus difficult to analyze, a simplified blast injury model would facilitate studies correlating biological outcomes with blast biomechanics to define tolerance criteria. Blast-induced traumatic brain injury (bTBI) results from the translation of a shock wave in-air, such as that produced by an IED, into a pressure wave within the skull-brain complex. Our blast injury methodology recapitulates this phenomenon in vitro, allowing for control of the injury biomechanics via a compressed-gas shock tube used in conjunction with a custom-designed, fluid-filled receiver that contains the living culture. The receiver converts the air shock wave into a fast-rising pressure transient with minimal reflections, mimicking the intracranial pressure history in blast. We have developed an organotypic hippocampal slice culture model that exhibits cell death when exposed to a 530 ± 17.7-kPa peak overpressure with a 1.026 ± 0.017-ms duration and 190 ± 10.7 kPa-ms impulse in-air. We have also injured a simplified in vitro model of the blood-brain barrier, which exhibits disrupted integrity immediately following exposure to 581 ± 10.0 kPa peak overpressure with a 1.067 ± 0.006-ms duration and 222 ± 6.9 kPa-ms impulse in-air. To better prevent and treat bTBI, both the initiating biomechanics and the ensuing pathobiology must be understood in greater detail. A well-characterized, in vitro model of bTBI, in conjunction with animal models, will be a powerful tool for developing strategies to mitigate the risks of bTBI.

Language: en

LA - en SN - 1664-2295 UR - http://dx.doi.org/10.3389/fneur.2012.00023 ID - ref1 ER -