Novel Model to Investigate Blast Injury in the Central Nervous System

Connell, Sean; Gao, Jian; Shi, Riyi

doi:10.1089/neu.2011.1832

Cited by 22 publications

(18 citation statements)

References 28 publications

(36 reference statements)

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“…Previously published in vitro models of bTBI have reported the incident overpressure of the blast wave but not the loading conditions at the tissue-level (Leung et al, 2008; Arun et al, 2011; Connell et al, 2011). Without a tissue-level biomechanical context, it is difficult to make quantitative comparisons between biological outcomes from different studies given the potential for vastly different loading conditions.…”

Section: Discussionmentioning

confidence: 99%

“…The injury biomechanics at the sample-level were not reported. In a different in vitro blast injury model, the excised spinal cord was subjected to strains as high as 60% with a jet of gas produced by a blast tube, which did not accurately reproduce the low strain, high strain rate biomechanics of blast (Connell et al, 2011). In each of these previous studies, overpressures were applied directly to the culture preparations, so the loading conditions were not representative of internal physiological loading conditions.…”

Section: Discussionmentioning

confidence: 99%

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A Multiscale Approach to Blast Neurotrauma Modeling: Part II: Methodology for Inducing Blast Injury to in vitro Models

Effgen¹,

Hue²,

Vogel³

et al. 2012

Front. Neur.

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Multiscale Approach to Blast Neurotrauma Modeling: Part II: Methodology for Inducing Blast Injury to in vitro Models

Effgen¹,

Hue²,

Vogel³

et al. 2012

Front. Neur.

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“…Their methodology consisted of exposing a 96 well plate of cell cultures sealed with a gas permeable membrane to air-driven shock tube blasts of 94, 125, and 145 kPa peak incident overpressure (overpressure duration not provided), although actual pressures exposed to the cell cultures inside the blasted plate were not reported. Connell et al (2011) developed an in vitro model of the isolated guinea pig spinal cord exposed to blast overpressures and found a reduction in the conduction of action potentials and a decrease in membrane integrity (Connell et al, 2011). Their test methodology consisted of exposing an isolated spinal cord directly to a jet of gas produced by a blast tube with overpressure levels of 23, 41, and 65 kPa peak incident pressure (0.2 ms duration for all blasts).…”

Section: Discussionmentioning

confidence: 99%

A Multiscale Approach to Blast Neurotrauma Modeling: Part I – Development of Novel Test Devices for in vivo and in vitro Blast Injury Models

Panzer¹,

Matthews²,

Yu³

et al. 2012

Front. Neur.

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The loading conditions used in some current in vivo and in vitro blast-induced neurotrauma models may not be representative of real-world blast conditions. To address these limitations, we developed a compressed-gas driven shock tube with different driven lengths that can generate Friedlander-type blasts. The shock tube can generate overpressures up to 650 kPa with durations between 0.3 and 1.1 ms using compressed helium driver gas, and peak overpressures up to 450 kPa with durations between 0.6 and 3 ms using compressed nitrogen. This device is used for short-duration blast overpressure loading for small animal in vivo injury models, and contrasts the more frequently used long duration/high impulse blast overpressures in the literature. We also developed a new apparatus that is used with the shock tube to recreate the in vivo intracranial overpressure response for loading in vitro culture preparations. The receiver device surrounds the culture with materials of similar impedance to facilitate the propagation of a single overpressure pulse through the tissue. This method prevents pressure waves reflecting off the tissue that can cause unrealistic deformation and injury. The receiver performance was characterized using the longest helium-driven shock tube, and produced in-fluid overpressures up to 1500 kPa at the location where a culture would be placed. This response was well correlated with the overpressure conditions from the shock tube (R2 = 0.97). Finite element models of the shock tube and receiver were developed and validated to better elucidate the mechanics of this methodology. A demonstration exposing a culture to the loading conditions created by this system suggest tissue strains less than 5% for all pressure levels simulated, which was well below functional deficit thresholds for strain rates less than 50 s−1. This novel system is not limited to a specific type of culture model and can be modified to reproduce more complex pressure pulses.

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“…However, results from experimental studies using animal models of blast exposure have demonstrated that direct blast shockwave is capable of penetrating the calvarium [Chavko et al, 2007] and can induce high strain rates leading to structural deficits such as axonal membrane disruption [Connell et al, 2011], myelin disruption, and neuronal death [Cernak et al, 2001;Saljo et al, 2002], as well as altered brain function .…”

Section: Introductionmentioning

confidence: 99%

Compromised Neurocircuitry in Chronic Blast‐Related Mild Traumatic Brain Injury

Yeh

Koay

Wang

et al. 2016

Human Brain Mapping

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The aim of this study was to apply recently developed automated fiber segmentation and quantification methods using diffusion tensor imaging (DTI) and DTI-based deterministic and probabilistic tractography to access local and global diffusion changes in blast-induced mild traumatic brain injury (bmTBI). Two hundred and two (202) male active US service members who reported persistent post-concussion symptoms for more than 6 months after injury were recruited. An additional forty (40) male military controls were included for comparison. DTI results were examined in relation to post-concussion and post-traumatic stress disorder (PTSD) symptoms. No significant group difference in DTI metrics was found using voxel-wise analysis. However, group comparison using tract profile analysis and tract specific analysis, as well as single subject analysis using tract profile analysis revealed the most prominent white matter microstructural injury in chronic bmTBI patients over the frontal fiber tracts, that is, the front-limbic projection fibers (cingulum bundle, uncinate fasciculus), the fronto-parieto-temporal association fibers (superior longitudinal fasciculus), and the fronto-striatal pathways (anterior thalamic radiation). Effects were noted to be sensitive to the number of previous blast exposures, with a negative association between fractional anisotropy (FA) and time since most severe blast exposure in a subset of the multiple blast-exposed group. However, these patterns were not observed in the subgroups classified using macrostructural changes (T2 white matter hyperintensities). Moreover, post-concussion symptoms and PTSD symptoms, as well as neuropsychological function were associated with low FA in the major nodes of compromised neurocircuitry. Hum Brain Mapp 38:352-369, 2017. © 2016 Wiley Periodicals, Inc.

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Novel Model to Investigate Blast Injury in the Central Nervous System

Cited by 22 publications

References 28 publications

A Multiscale Approach to Blast Neurotrauma Modeling: Part II: Methodology for Inducing Blast Injury to in vitro Models

A Multiscale Approach to Blast Neurotrauma Modeling: Part II: Methodology for Inducing Blast Injury to in vitro Models

A Multiscale Approach to Blast Neurotrauma Modeling: Part I – Development of Novel Test Devices for in vivo and in vitro Blast Injury Models

Compromised Neurocircuitry in Chronic Blast‐Related Mild Traumatic Brain Injury

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