Research Papers

Significant Head Accelerations Can Influence Immediate Neurological Impairments in a Murine Model of Blast-Induced Traumatic Brain Injury

[+] Author and Article Information
David M. Gullotti, Matthew Beamer, Yung Chia Chen, Tapan P. Patel, Nicolas Jaumard

Department of Bioengineering,
University of Pennsylvania,
240 Skirkanich Hall,
210 S. 33rd Street,
Philadelphia, PA 19104-6321

Matthew B. Panzer, Allen Yu, Cameron R. Bass

Department of Biomedical Engineering,
Duke University,
Durham, NC 27708

Beth Winkelstein, David F. Meaney

Department of Bioengineering,
University of Pennsylvania,
240 Skirkanich Hall,
210 S. 33rd Street,
Philadelphia, PA 19104-6321
Department of Neurosurgery,
University of Pennsylvania,
Philadelphia, PA 19104

Barclay Morrison

Department of Biomedical Engineering,
Columbia University,
New York, NY 10027

1Corresponding author.

Manuscript received June 21, 2013; final manuscript received June 11, 2014; accepted manuscript posted June 19, 2014; published online July 10, 2014. Assoc. Editor: Brian D. Stemper.

J Biomech Eng 136(9), 091004 (Jul 10, 2014) (11 pages) Paper No: BIO-13-1274; doi: 10.1115/1.4027873 History: Received June 21, 2013; Revised June 11, 2014; Accepted June 19, 2014

Although blast-induced traumatic brain injury (bTBI) is well recognized for its significance in the military population, the unique mechanisms of primary bTBI remain undefined. Animate models of primary bTBI are critical for determining these potentially unique mechanisms, but the biomechanical characteristics of many bTBI models are poorly understood. In this study, we examine some common shock tube configurations used to study blast-induced brain injury in the laboratory and define the optimal configuration to minimize the effect of torso overpressure and blast-induced head accelerations. Pressure transducers indicated that a customized animal holder successfully reduced peak torso overpressures to safe levels across all tested configurations. However, high speed video imaging acquired during the blast showed significant head accelerations occurred when animals were oriented perpendicular to the shock tube axis. These findings of complex head motions during blast are similar to previous reports [Goldstein et al., 2012, “Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model,” Sci. Transl. Med., 4(134), 134ra160; Sundaramurthy et al., 2012, “Blast-Induced Biomechanical Loading of the Rat: An Experimental and Anatomically Accurate Computational Blast Injury Model,” J. Neurotrauma, 29(13), pp. 2352–2364; Svetlov et al., 2010, “Morphologic and Biochemical Characterization of Brain Injury in a Model of Controlled Blast Overpressure Exposure,” J. Trauma, 69(4), pp. 795–804]. Under the same blast input conditions, minimizing head acceleration led to a corresponding elimination of righting time deficits. However, we could still achieve righting time deficits under minimal acceleration conditions by significantly increasing the peak blast overpressure. Together, these data show the importance of characterizing the effect of blast overpressure on head kinematics, with the goal of producing models focused on understanding the effects of blast overpressure on the brain without the complicating factor of superimposed head accelerations.

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Orman, J. A., Geyer, D., Jones, J., Schneider, E. B., Grafman, J., Pugh, M. J., and Dubose, J., 2012, “Epidemiology of Moderate-to-Severe Penetrating Versus Closed Traumatic Brain Injury in the Iraq and Afghanistan Wars,” J. Trauma Acute Care Surg., 73(6 Suppl 5), pp. S496–S502. [CrossRef] [PubMed]
Taniellan, T., and Jaycox, L. H., 2008, “Invisible Wounds of War: Psychological and Cognitive Injuries, Their Consequencesm and Services to Assist Recovery,” Report No. MG-720-CCF.
Bass, C. R., Panzer, M. B., Rafaels, K. A., Wood, G., Shridharani, J., and Capehart, B., 2012, “Brain Injuries From Blast,” Ann. Biomed. Eng., 40(1), pp. 185–202. [CrossRef] [PubMed]
Cernak, I., Wang, Z., Jiang, J., Bian, X., and Savic, J., 2001, “Ultrastructural and Functional Characteristics of Blast Injury-Induced Neurotrauma,” J. Trauma, 50(4), pp. 695–706. [CrossRef] [PubMed]
Sundaramurthy, A., Alai, A., Ganpule, S., Holmberg, A., Plougonven, E., and Chandra, N., 2012, “Blast-Induced Biomechanical Loading of the Rat: An Experimental and Anatomically Accurate Computational Blast Injury Model,” J. Neurotrauma, 29(13), pp. 2352–2364. [CrossRef] [PubMed]
Wang, Y., Wei, Y., Oguntayo, S., Wilkins, W., Arun, P., Valiyaveettil, M., Song, J., Long, J. B., and Nambiar, M. P., 2011, “Tightly Coupled Repetitive Blast-Induced Traumatic Brain Injury: Development and Characterization in Mice,” J. Neurotrauma, 28(10), pp. 2171–2183. [CrossRef] [PubMed]
Long, J. B., Bentley, T. L., Wessner, K. A., Cerone, C., Sweeney, S., and Bauman, R. A., 2009, “Blast Overpressure in Rats: Recreating a Battlefield Injury in the Laboratory,” J. Neurotrauma, 26(6), pp. 827–840. [CrossRef] [PubMed]
Baalman, K., Cotton, J., Rasband, N., and Rasband, M., 2012, “Blast Wave Exposure Impairs Memory and Decreases Axon Initial Segment Length,” J. Neurotrauma, 30(9), pp. 741–751. [CrossRef]
Shah, A. S., Stemper, B. D., and Pintar, F. A., 2012, “Development and Characterization of an Open-Ended Shock Tube for the Study of Blast mTBI,” Biomed. Sci. Instrum., 48, pp. 393–400. [PubMed]
Ahlers, S. T., Vasserman-Stokes, E., Shaughness, M. C., Hall, A. A., Shear, D. A., Chavko, M., McCarron, R. M., and Stone, J. R., 2012, “Assessment of the Effects of Acute and Repeated Exposure to Blast Overpressure in Rodents: Toward a Greater Understanding of Blast and the Potential Ramifications for Injury in Humans Exposed to Blast,” Front. Neurol., 3, p. 00032. [CrossRef]
Svetlov, S. I., Prima, V., Glushakova, O., Svetlov, A., Kirk, D. R., Gutierrez, H., Serebruany, V. L., Curley, K. C., Wang, K. K., and Hayes, R. L., 2012, “Neuro-Glial and Systemic Mechanisms of Pathological Responses in Rat Models of Primary Blast Overpressure Compared to “Composite” Blast,” Front. Neurol., 3, p. 00015. [CrossRef]
Effgen, G. B., Hue, C. D., Vogel, III, E. W., Panzer, M. B., Meaney, D. F., Bass, C. R., and Morrison, III, B., 2012, “A Multiscale Approach to Blast Neurotrauma Modeling: Part II: Methodology for Inducing Blast Injury to In Vitro Models,” Front. Neurol., 3, p. 00023. [CrossRef]
Arun, P., Abu-Taleb, R., Valiyaveettil, M., Wang, Y., Long, J. B., and Nambiar, M. P., 2012, “Transient Changes in Neuronal Cell Membrane Permeability After Blast Exposure,” Neuroreport, 23(6), pp. 342–346. [CrossRef] [PubMed]
Shridharani, J. K., Wood, G. W., Panzer, M. B., Capehart, B. P., Nyein, M. K., Radovitzky, R. A., and Bass, C. R., 2012, “Porcine Head Response to Blast,” Front. Neurol., 3, p. 00070. [CrossRef]
Liu, H., Kang, J., Chen, J., Li, G., Li, X., and Wang, J., 2012, “Intracranial Pressure Response to Non-Penetrating Ballistic Impact: An Experimental Study Using a Pig Physical Head Model and Live Pigs,” Int. J. Med. Sci., 9(8), pp. 655–664. [CrossRef] [PubMed]
Dal Cengio Leonardi, A., Keane, N. J., Bir, C. A., Ryan, A. G., Xu, L., and Vandevord, P. J., 2012, “Head Orientation Affects the Intracranial Pressure Response Resulting From Shock Wave Loading in the Rat,” ASME J. Biomech. Eng., 45(15), pp. 2595–2602. [CrossRef]
Ganpule, S., Alai, A., Plougonven, E., and Chandra, N., 2012, “Mechanics of Blast Loading on the Head Models in the Study of Traumatic Brain Injury Using Experimental and Computational Approaches,” Biomech. Model Mechanobiol.12(3), pp. 511–531. [CrossRef] [PubMed]
Leonardi, A. D., Bir, C. A., Ritzel, D. V., and VandeVord, P. J., 2011, “Intracranial Pressure Increases During Exposure to a Shock Wave,” J. Neurotrauma, 28(1), pp. 85–94. [CrossRef] [PubMed]
Goldstein, L. E., Fisher, A. M., Tagge, C. A., Zhang, X. L., Velisek, L., Sullivan, J. A., Upreti, C., Kracht, J. M., Ericsson, M., Wojnarowicz, M. W., Goletiani, C. J., Maglakelidze, G. M., Casey, N., Moncaster, J. A., Minaeva, O., Moir, R. D., Nowinski, C. J., Stern, R. A., Cantu, R. C., Geiling, J., Blusztajn, J. K., Wolozin, B. L., Ikezu, T., Stein, T. D., Budson, A. E., Kowall, N. W., Chargin, D., Sharon, A., Saman, S., Hall, G. F., Moss, W. C., Cleveland, R. O., Tanzi, R. E., Stanton, P. K., and McKee, A. C., 2012, “Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model,” Sci. Transl. Med., 4(134), p. 134ra160. [CrossRef]
Svetlov, S. I., Prima, V., Kirk, D. R., Gutierrez, H., Curley, K. C., Hayes, R. L., and Wang, K. K., 2010, “Morphologic and Biochemical Characterization of Brain Injury in a Model of Controlled Blast Overpressure Exposure,” J. Trauma, 69(4), pp. 795–804. [CrossRef] [PubMed]
Budde, M. D., Shah, A., McCrea, M., Cullinan, W. E., Pintar, F. A., and Stemper, B. D., 2013, “Primary Blast Traumatic Brain Injury in the Rat: Relating Diffusion Tensor Imaging and Behavior,” Front. Neurol., 4, p. 00154. [CrossRef]
Panzer, M. B., Matthews, K. A., Yu, A. W., Morrison, III, B., Meaney, D. F., and Bass, C. R., 2012, “A Multiscale Approach to Blast Neurotrauma Modeling: Part I - Development of Novel Test Devices for In Vivo and In Vitro Blast Injury Models,” Front. Neurol., 3, p. 00046. [CrossRef]
Hallam, T. M., Floyd, C. L., Folkerts, M. M., Lee, L. L., Gong, Q. Z., Lyeth, B. G., Muizelaar, J. P., and Berman, R. F., 2004, “Comparison of Behavioral Deficits and Acute Neuronal Degeneration in Rat Lateral Fluid Percussion and Weight-Drop Brain Injury Models,” J. Neurotrauma, 21(5), pp. 521–539. [CrossRef] [PubMed]
Hayes, R. L., Jenkins, L. W., Lyeth, B. G., Balster, R. L., Robinson, S. E., Clifton, G. L., Stubbins, J. F., and Young, H. F., 1988, “Pretreatment With Phencyclidine, an N-Methyl-D-Aspartate Antagonist, Attenuates Long-Term Behavioral Deficits in the Rat Produced by Traumatic Brain Injury,” J. Neurotrauma, 5(4), pp. 259–274. [CrossRef] [PubMed]
Kane, M. J., Angoa-Perez, M., Briggs, D. I., Viano, D. C., Kreipke, C. W., and Kuhn, D. M., 2012, “A Mouse Model of Human Repetitive Mild Traumatic Brain Injury,” J. Neurosci. Methods, 203(1), pp. 41–49. [CrossRef] [PubMed]
Friedlander, F. G., 1946, “The Diffraction of Sound Pulses; Diffraction by a Semi-Infinite Plane,” Proc. R. Soc., London, Sec. A, 186(1006), pp. 322–344. [CrossRef]
Bass, C. R., Rafaels, K. A., and Salzar, R. S., 2008, “Pulmonary Injury Risk Assessment for Short-Duration Blasts,” J. Trauma, 65(3), pp. 604–615. [CrossRef] [PubMed]
Valiyaveettil, M., Alamneh, Y. A., Miller, S. A., Hammamieh, R., Arun, P., Wang, Y., Wei, Y., Oguntayo, S., Long, J. B., and Nambiar, M. P., 2013, “Modulation of Cholinergic Pathways and Inflammatory Mediators in Blast-Induced Traumatic Brain Injury,” Chem. Biol. Interact.203(1), pp. 371–375. [CrossRef] [PubMed]
Arun, P., Oguntayo, S., Alamneh, Y., Honnold, C., Wang, Y., Valiyaveettil, M., Long, J. B., and Nambiar, M. P., 2012, “Rapid Release of Tissue Enzymes Into Blood After Blast Exposure: Potential Use as Biological Dosimeters,” PloS one, 7(4), p. e33798. [CrossRef] [PubMed]
Koliatsos, V. E., Cernak, I., Xu, L., Song, Y., Savonenko, A., Crain, B. J., Eberhart, C. G., Frangakis, C. E., Melnikova, T., Kim, H., and Lee, D., 2011, “A Mouse Model of Blast Injury to Brain: Initial Pathological, Neuropathological, and Behavioral Characterization,” J. Neuropathol. Exp. Neurol., 70(5), pp. 399–416. [CrossRef] [PubMed]
Risling, M., Plantman, S., Angeria, M., Rostami, E., Bellander, B. M., Kirkegaard, M., Arborelius, U., and Davidsson, J., 2011, “Mechanisms of Blast Induced Brain Injuries, Experimental Studies in Rats,” NeuroImage, 54(Suppl 1), pp. S89–S97. [CrossRef] [PubMed]
Cernak, I., Merkle, A. C., Koliatsos, V. E., Bilik, J. M., Luong, Q. T., Mahota, T. M., Xu, L., Slack, N., Windle, D., and Ahmed, F. A., 2011, “The Pathobiology of Blast Injuries and Blast-Induced Neurotrauma as Identified Using a New Experimental Model of Injury in Mice,” Neurobiol. Disease, 41(2), pp. 538–551. [CrossRef]
Vandevord, P. J., Bolander, R., Sajja, V. S., Hay, K., and Bir, C. A., 2012, “Mild Neurotrauma Indicates a Range-Specific Pressure Response to Low Level Shock Wave Exposure,” Ann. Biomed. Eng., 40(1), pp. 227–236. [CrossRef] [PubMed]
Bolander, R., Mathie, B., Bir, C., Ritzel, D., and VandeVord, P., 2011, “Skull Flexure as a Contributing Factor in the Mechanism of Injury in the Rat When Exposed to a Shock Wave,” Ann. Biomed. Eng., 39(10), pp. 2550–2559. [CrossRef] [PubMed]
Saljo, A., Bolouri, H., Mayorga, M., Svensson, B., and Hamberger, A., 2010, “Low-Level Blast Raises Intracranial Pressure and Impairs Cognitive Function in Rats: Prophylaxis With Processed Cereal Feed,” J. Neurotrauma, 27(2), pp. 383–389. [CrossRef] [PubMed]
Chavko, M., Watanabe, T., Adeeb, S., Lankasky, J., Ahlers, S. T., and McCarron, R. M., 2011, “Relationship Between Orientation to a Blast and Pressure Wave Propagation Inside the Rat Brain,” J. Neurosci. Methods, 195(1), pp. 61–66. [CrossRef] [PubMed]
Chavko, M., Koller, W. A., Prusaczyk, W. K., and McCarron, R. M., 2007, “Measurement of Blast Wave by a Miniature Fiber Optic Pressure Transducer in the Rat Brain,” J. Neurosci. Methods, 159(2), pp. 277–281. [CrossRef] [PubMed]
Dal Cengio Leonardi, A., Keane, N. J., Hay, K., Ryan, A. G., Bir, C. A., and VandeVord, P. J., 2013, “Methodology and Evaluation of Intracranial Pressure Response in Rats Exposed to Complex Shock Waves,” Ann. Biomed. Eng., 41(12), pp. 2488–2500. [CrossRef] [PubMed]
Skotak, M., Wang, F., Alai, A., Holmberg, A., Harris, S., Switzer, R. C., and Chandra, N., 2013, “Rat Injury Model Under Controlled Field-Relevant Primary Blast Conditions: Acute Response to a Wide Range of Peak Overpressures,” J. Neurotrauma, 30(13), pp. 1147–1160. [CrossRef] [PubMed]
Yu, A. W., Wang, H., Matthews, K. A., Rafaels, K. A., Laskowitz, D. T., Gullotti, D., Meaney, D. F., Morrison, III, B., and Bass, C. R., 2012, “Mouse Lethality Risk and Intracranial Pressure During Exposure to Blast,” Biomedical Engineering Society Annual Meeting, BMES, Atlanta, GA, Oct. 24–27.
Pellman, E. J., Viano, D. C., Tucker, A. M., and Casson, I. R., 2003, “Concussion in Professional Football: Location and Direction of Helmet Impacts-Part 2,” Neurosurgery, 53(6), pp. 1328–1340; discussion 1340–1321. [CrossRef] [PubMed]
Zhang, L., Yang, K. H., and King, A. I., 2004, “A Proposed Injury Threshold for Mild Traumatic Brain Injury,” ASME J. Biomech. Eng., 126(2), pp. 226–236. [CrossRef]
Meaney, D. F., Smith, D. H., Shreiber, D. I., Bain, A. C., Miller, R. T., Ross, D. T., and Gennarelli, T. A., 1995, “Biomechanical Analysis of Experimental Diffuse Axonal Injury,” J. Neurotrauma, 12(4), pp. 689–694. [CrossRef] [PubMed]
Kuehn, R., Simard, P. F., Driscoll, I., Keledjian, K., Ivanova, S., Tosun, C., Williams, A., Bochicchio, G., Gerzanich, V., and Simard, J. M., 2011, “Rodent Model of Direct Cranial Blast Injury,” J. Neurotrauma, 28(10), pp. 2155–2169. [CrossRef] [PubMed]
Nakagawa, A., Fujimura, M., Kato, K., Okuyama, H., Hashimoto, T., Takayama, K., and Tominaga, T., 2008, “Shock Wave-Induced Brain Injury in Rat: Novel Traumatic Brain Injury Animal Model,” Acta Neurochir. Suppl., 102, pp. 421–424. [CrossRef] [PubMed]


Grahic Jump Location
Fig. 1

Diagrams representing the different animal orientations relative to the blast tube. All orientations held the distance from the exit of the tube to the center of the mouse head constant. (a) Perpendicular orientation with the center of the mouse head aligned with the center of the tube's axis. The location of the Sorbothane base indicated is consistent in all orientations. (b) The same perpendicular orientation used in (a) with the mouse's head aligned with the inner periphery of the tube. (c) Angled orientation with the mouse head aligned with the inner periphery of the tube. (d) Parallel orientation with the mouse head constrained by a Sorbothane-lined collar.

Grahic Jump Location
Fig. 2

Shock tube characterization. Pressure transducers located along different points within and outside the tube (a) were used to measure the static pressure during a blast event. For measures outside the tube, the transducers were located at the same radial location as the tube wall. Additionally, small elastic cylinders were inserted into the path of the blast waves, extending slightly from the tube wall. The blast wind traveling across these elastic cylinders caused the cylinder to deflect ((b), shown for regions outlined in (a)). The magnitude of the peak displacement of the tip is shown for each region; no significant difference in deflection occurred across the four observation points. (c) Measures of pressure within (−38 mm) and outside (+15 mm) showed a slight attenuation of the peak pressure and a more dramatic reduction in the duration. (d) Across the distances beyond the tube exit that contained the animal head, there was significant differences to the peak pressure, duration, and impulse (grayed regions in each plot denote range (mean ± SD) of pressure profile characteristics within the tube.).

Grahic Jump Location
Fig. 3

Representative pressure traces gathered from the three sensors at the exit of the blast tube with the mouse holder in different positions. All tests were conducted in the perpendicular orientation. Under each trace is a top view of the corresponding animal holder position relative to the blast tube. Both centered ((a)–(c)) and retracted ((d)–(f)) positions were tested without obstruction, with only the mouse holder, and with both the holder and mouse present. Traces are color coded to match the corresponding diagrams.

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Fig. 4

Displacement that occurs during each blast event for the perpendicular ((b); n = 6), angled ((d); n = 4), and parallel ((f); n = 4) orientations. Different color traces represent different trials in the same orientation. Schematic diagrams ((a), (c), and (e)) of the mouse head position, extracted from high speed video recordings, prior to blast exposure. (b) Vertical (y) movement of the head in the perpendicular configuration is consistent during the first phase of motion (initial position denoted by dot) and shows more variability in lateral movement across tests. (d) Angled positioning of the head relative to the incoming blast wave reduced motion substantially when compared to the perpendicular position. (e) The most limited head motion occurred when the animal was oriented parallel to the shock tube, and the head was supported with a cervical collar. Blast input conditions were kept consistent across tests (average blast overpressure = 215 ± 13 kPa, average blast duration = 0.65 ± 0.04 ms, and average blast impulse = 46 ± 5 kPa·ms). Results are reported as mean ± SD.

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Fig. 5

Horizontal ((a)–(c)) and vertical ((d)-(f)) components of motion resulting from a blast exposure with the mouse aligned perpendicular to the incoming blast wave, and positioned along the periphery of the shock tube (Fig. 1(b)). Position graphs ((a) and (d)) display both the original data (black circles) and filtered output (black line). Velocities ((b) and (e)) and accelerations ((c) and (f)) were calculated from the filtered displacement data. Peak resultant accelerations were significantly higher when the animal was placed perpendicular to the direction of the blast wave (g). SDs are indicated (g). Asterisk (*) indicates a significant difference (p < 0.05) based on posthoc testing between the perpendicular condition and angled and parallel groups. The angled and parallel groups were not significantly different from each other.

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Fig. 6

Induced head acceleration influences survival and immediate neurological impairment following blast exposure. (a) Fatality data (0 = survive; 1 = fatal) for two biomechanical scenarios—(1) a blast wave transmitting an intracranial pressure change and a significant head acceleration (perpendicular orientation), and (2) a blast wave that only transmitted an intracranial pressure change, with reduced head acceleration (angled and parallel orientations). Logistic regression analysis on the survival data showed that the lowest survival thresholds appeared when the head was allowed to move during the blast event ((a) and (b)). Significant differences in the blast overpressure and impulse for 50% survival probability appeared across all three orientations. Numbers correspond to the pressure/impulse associated with 50% fatality in each configuration. (c) Righting times normalized to sham for the perpendicular and parallel orientations. For equivalent blast overpressures that caused only transient impairment (215 ± 13 kPa), restraining the head led to a complete loss of functional impairment after blast exposure. However, it was possible to cause a significant righting time deficit even when the head was constrained, although the necessary blast overpressure levels (415 ± 41 kPa) were significantly higher than the unrestrained head motion tests. (N = 10–13 animals/group; average ± standard error shown).

Grahic Jump Location
Fig. 7

Brain injury patterns in surviving animals. Following blast exposure in either the perpendicular or parallel orientation, animals showed no signs of bleeding along the surface of the brain. Moreover, there was no sign of subarachnoid hemorrhage or primary brainstem damage. There was no apparent difference in overt changes to the brain following two different levels of blast exposure (parallel orientation). Images of the lungs showed no macroscopic signs of hemorrhage. All samples were collected 15 min following blast exposure.




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