A multiscale approach to blast neurotrauma modeling:Part II: Methodology for inducing blast injury to in vitro models
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, m...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2012-02-01
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| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fneur.2012.00023/full |
| _version_ | 1818271750731857920 |
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| author | Gwen B. Effgen Christopher D. Hue Edward eVogel Matthew B Panzer David F. Meaney Cameron 'Dale' R. Bass Barclay eMorrison |
| author_facet | Gwen B. Effgen Christopher D. Hue Edward eVogel Matthew B Panzer David F. Meaney Cameron 'Dale' R. Bass Barclay eMorrison |
| author_sort | Gwen B. Effgen |
| collection | DOAJ |
| description | 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 ms ± 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. |
| first_indexed | 2024-12-12T21:31:08Z |
| format | Article |
| id | doaj.art-3a6a12bdff4e4b8b8b91d20660da24f1 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-12T21:31:08Z |
| publishDate | 2012-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-3a6a12bdff4e4b8b8b91d20660da24f12022-12-22T00:11:19ZengFrontiers Media S.A.Frontiers in Neurology1664-22952012-02-01310.3389/fneur.2012.0002318399A multiscale approach to blast neurotrauma modeling:Part II: Methodology for inducing blast injury to in vitro modelsGwen B. Effgen0Christopher D. Hue1Edward eVogel2Matthew B Panzer3David F. Meaney4Cameron 'Dale' R. Bass5Barclay eMorrison6Columbia UniversityColumbia UniversityColumbia UniversityDuke UniversityUniversity of PennsylvaniaDuke UniversityColumbia UniversityDue 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 ms ± 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.http://journal.frontiersin.org/Journal/10.3389/fneur.2012.00023/fullBlood-Brain BarrierEndothelial CellsHippocampusblast injuryNeuronastrocyte |
| spellingShingle | Gwen B. Effgen Christopher D. Hue Edward eVogel Matthew B Panzer David F. Meaney Cameron 'Dale' R. Bass Barclay eMorrison A multiscale approach to blast neurotrauma modeling:Part II: Methodology for inducing blast injury to in vitro models Frontiers in Neurology Blood-Brain Barrier Endothelial Cells Hippocampus blast injury Neuron astrocyte |
| title | A multiscale approach to blast neurotrauma modeling:Part II: Methodology for inducing blast injury to in vitro models |
| title_full | A multiscale approach to blast neurotrauma modeling:Part II: Methodology for inducing blast injury to in vitro models |
| title_fullStr | A multiscale approach to blast neurotrauma modeling:Part II: Methodology for inducing blast injury to in vitro models |
| title_full_unstemmed | A multiscale approach to blast neurotrauma modeling:Part II: Methodology for inducing blast injury to in vitro models |
| title_short | A multiscale approach to blast neurotrauma modeling:Part II: Methodology for inducing blast injury to in vitro models |
| title_sort | multiscale approach to blast neurotrauma modeling part ii methodology for inducing blast injury to in vitro models |
| topic | Blood-Brain Barrier Endothelial Cells Hippocampus blast injury Neuron astrocyte |
| url | http://journal.frontiersin.org/Journal/10.3389/fneur.2012.00023/full |
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