Skip to main content

Advertisement

Log in

Investigations of primary blast-induced traumatic brain injury

  • Original Article
  • Published:
Shock Waves Aims and scope Submit manuscript

Abstract

The development of an advanced blast simulator (ABS) has enabled the reproducible generation of single-pulse shock waves that simulate free-field blast with high fidelity. Studies with rodents in the ABS demonstrated the necessity of head restraint during head-only exposures. When the head was not restrained, violent global head motion was induced by pressures that would not produce similar movement of a target the size and mass of a human head. This scaling artefact produced changes in brain function that were reminiscent of traumatic brain injury (TBI) due to impact-acceleration effects. Restraint of the rodent head eliminated these, but still produced subtle changes in brain biochemistry, showing that blast-induced pressure waves do cause brain deficits. Further experiments were carried out with rat brain cell aggregate cultures that enabled the conduct of studies without the gross movement encountered when using rodents. The suspension nature of this model was also exploited to minimize the boundary effects that complicate the interpretation of primary blast studies using surface cultures. Using this system, brain tissue was found not only to be sensitive to pressure changes, but also able to discriminate between the highly defined single-pulse shock waves produced by underwater blast and the complex pressure history exposures experienced by aggregates encased within a sphere and subjected to simulated air blast. The nature of blast-induced primary TBI requires a multidisciplinary research approach that addresses the fidelity of the blast insult, its accurate measurement and characterization, as well as the limitations of the biological models used.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Ling, G., Bandak, F., Armonda, R., Grant, G., Ecklund, J.: Explosive blast neurotrauma. J. Neurotrauma 26, 815–825 (2009). doi:10.1089/neu.2007.0484

    Article  Google Scholar 

  2. Tanielian, T., Jaycox, L.H., Schell, T.L., Marshall, G.N., Burnam, M.A., Eibner, C., Karney, B.R., Meredith, L.S., Ringel, J.S., Vaiana, M.E.: Invisible Wounds of War. Psychological and Cognitive Injuries, Their Consequences, and Services to Assist Recovery. RAND Corp, Santa Monica (2008)

    Book  Google Scholar 

  3. Elder, G.A., Stone, J.R., Ahlers, S.T.: Effects of low-level blast exposure on the nervous system: Is there really a controversy? Front. Neurol. 5, 269 (2014). doi:10.3389/fneur.2014.00269

    Article  Google Scholar 

  4. Warden, D.L., French, L.M., Shupenko, L., Fargus, J., Riedy, G., Erickson, M.E., Jaffee, M.S., Moore, D.F.: Case report of a soldier with primary blast brain injury. Neuroimage 47, T152–T153 (2009). doi:10.1016/j.neuroimage.2009.01.060

    Article  Google Scholar 

  5. Guy, R.J., Glover, M.A., Cripps, N.P.J.: Primary blast injury: pathophysiology and implications for treatment. Part III: Injury to the central nervous system and the limbs. J. R. Nav. Serv. 86, 27–31 (2000)

    Google Scholar 

  6. Yilmaz, S., Pekdemir, M.: An unusual primary blast injury: Traumatic brain injury due to primary blast. Am. J. Emerg. Med. 25, 97–98 (2007). doi:10.1016/j.ajem.2006.04.014

    Article  Google Scholar 

  7. Elder, G.A., Mitsis, E.M., Ahlers, S.T., Cristian, A.: Blast-induced mild traumatic brain injury. Psychiatr. Clin. N. Am. 33, 757–781 (2010). doi:10.1016/j.psc.2010.08.001

    Article  Google Scholar 

  8. Palma, J.: Blast injury of the lungs. With comment on immersion blast injury. Hawaii Med. J. 10, 42–44 (1942)

    Google Scholar 

  9. Palma, J., Uldall, J.J.: Immersion blast injuries. US Nav. Med. Bull. 41, 3–8 (1943)

    Google Scholar 

  10. Pugh, H.L.: Surgical report on immersion blast injuries. US Nav. Med. Bull. 41, 9–12 (1943)

    Google Scholar 

  11. Yaguda, A.: Pathology of immersion blast injury. US Nav. Med. Bull. 44, 232–240 (1945)

    Google Scholar 

  12. Clark, S.L., Ward, J.W.: The effects of rapid compression waves on animals submerged in water. Surg. Gynecol. Obstet. 77, 403–412 (1943)

    Google Scholar 

  13. Freidell, M.T., Ecklund, A.M.: Experimental immersion blast injury. Preliminary report. US Nav. Med. Bull. 41, 353–363 (1943)

    Google Scholar 

  14. Cudahy, E., Parvin, S.: The Effects of Underwater Blast on Divers. Naval Submarine Medical Research Laboratory, NSMRL Report 1218, pp. 1–62 (2001)

  15. Hooker, D.R.: Physiological effects of air concussion. Am. J. Physiol. 67, 219–374 (1924)

    Google Scholar 

  16. Cassen, B., Kistler, K., Mankiewicz, W.: Some effects of air blast on mechanically constrained mice. J. Aviat. Med. 23, 120–129 (1952)

    Google Scholar 

  17. Zuckerman, S.: Experimental study of blast injuries to the lungs. Lancet 236, 219–224 (1940). doi:10.1016/S0140-6736(01)08726-8

    Article  Google Scholar 

  18. DePalma, R., Burris, D.G., Champion, H.R., Hodgson, M.J.: Blast injuries. N. Engl. J. Med. 352, 1335–1342 (2005). doi:10.1056/NEJMra042083

    Article  Google Scholar 

  19. Katz, E., Ofek, B., Adler, J., Abramowitz, H.B., Krausz, M.M.: Primary blast injury after a bomb explosion in a civilian bus. Ann. Surg. 209, 484–488 (1989)

    Article  Google Scholar 

  20. Coppel, D.L.: Blast injuries of the lungs. Br. J. Surg. 63, 735–737 (1976). doi:10.1002/bjs.1800631003

    Article  Google Scholar 

  21. Yang, Z., Wang, Z., Tang, C., Ying, Y.: Biological effects of weak blast waves and safety limits for internal organ injury in the human body. J. Trauma 40(Suppl. 3), S81–S84 (1996)

    Article  Google Scholar 

  22. Jones, E., Fear, N.T., Wessely, S.: Shell shock and mild traumatic brain injury: A historical review. Am. J. Psychiatr. 164, 1641–1645 (2007). doi:10.1176/appi.ajp.2007.07071180

    Article  Google Scholar 

  23. Myers, C.J.: A contribution to the study of shell shock. Lancet 185(4772), 316–320 (1915). doi:10.1016/S0140-6736(00)52916-X

    Article  Google Scholar 

  24. Mott, F.W.: The effects of high explosives upon the central nervous system. Lancet 187, 331–338; 441–449; 545–553 (1916). doi:10.1016/S0140-6736(00)52963-8, 10.1016/S0140-6736(01)11159-1, 10.1016/S0140-6736(01)11370-X

  25. Mott, F.W.: The microscopic examination of the brains of two men dead of commotio cerebri (shell shock) without visible external injury. Br. Med. J. 2, 612–615 (1917)

    Article  Google Scholar 

  26. Mott, F.W.: Mental hygiene in shell shock during and after the war. Br. Med. J. 2, 39–42 (1917)

    Article  Google Scholar 

  27. Clemedson, C.-J.: Shock wave transmission in the central nervous system. Acta Physiol. Scand. 37, 204–214 (1956). doi:10.1111/j.1748-1716.1956.tb01356.x

    Article  Google Scholar 

  28. Zuckerman, S.: Discussion of the problem of blast injuries. Proc. R. Soc. Med. 34, 171–192 (1941)

    Google Scholar 

  29. Fulton, J.F.: Blast and concussion in the present war. N. Engl. J. Med. 226, 1–8 (1942). doi:10.1056/NEJM194201012260101

    Article  Google Scholar 

  30. Reid, F.: “His nerves gave way”: Shell shock, history and the memory of the First World War in Britain. Endevour 38, 91–100 (2014). doi:10.1016/j.endeavour.2014.05.002

    Article  Google Scholar 

  31. Elder, G.A., Cristian, A.: Blast-related mild traumatic brain injury: Mechanisms of injury and impact on critical care. Mt. Sinai J. Med. 76, 111–118 (2009). doi:10.1002/msj.20098

    Article  Google Scholar 

  32. Vasterling, J.J., Verfaielle, M., Sullivan, K.D.: Mild traumatic brain injury and posttraumatic stress disorder in returning veterans: Perspectives from cognitive neuroscience. Clin. Psychol. Rev. 29, 674–684 (2009). doi:10.1016/j.cpr.2009.08.004

    Article  Google Scholar 

  33. Champion, H.R., Holcomb, J.B., Young, L.A.: Injuries from explosions: Physics, biophysics, and required research focus. J. Trauma 66, 1468–1477 (2009). doi:10.1097/TA.0b013e3181a27e7f

    Article  Google Scholar 

  34. Hoge, C.W., McGurk, D., Thomas, J.L., Cox, A.L., Engel, C.C., Castro, C.A.: Mild traumatic brain injury in U.S. soldiers returning from Iraq. N. Engl. J. Med. 358, 453–463 (2008). doi:10.1056/NEJMoa072972

    Article  Google Scholar 

  35. Gean, A.D.: Blast injury basics. In: Pine Jr., J.W., Shaw, R., Dinkel, A.G. (eds.) Chapter 3: Brain Injury. Applications from War and Terrorism. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia (2014)

  36. Ritzel, D.V., Parks, S.A, Roseveare, J., Rude, G., Sawyer, T.W.: Experimental blast simulation for injury studies. In: Proceedings of NATO HFM 207, Halifax (2011)

  37. Needham, C.E., Ritzel, D., Rule, G.T., Wiri, S., Young, L.: Blast testing issues and TBI: Experimental models that lead to wrong conclusions. Front. Neurol. 6, 72 (2015). doi:10.3389/fneur.2015.00072

    Article  Google Scholar 

  38. Sawyer, T.W., Wang, Y., Ritzel, D.V., Josey, T., Villanueva, M., Shei, Y., Nelson, P., Hennes, G., Weiss, T., Vair, C., Fan, C., Barnes, J.: High-fidelity simulation of primary blast: direct effects on the head. J. Neurotrauma 33, 1181–1191 (2016). doi:10.1089/neu.2015.3914

    Article  Google Scholar 

  39. Chandra, N., Sundaramurthy, A.: Acute pathophysiology of blast injury-from biomechanics to experiments and computations: implications on head and polytrauma. In: Kobeissy, F.H. (ed.) Chapter 18: Brain Neurotrauma. Molecular, Neuropsychological and Rehabilitation Aspects. CRC Press/Taylor & Francis, Boca Raton (2016)

    Google Scholar 

  40. Arun, P., Spadaro, J., John, J., Gharavi, R.B., Bentley, T.B., Nambiar, M.P.: Studies on blast traumatic brain injury using in-vitro model with shock tube. NeuroReport 22, 379–384 (2011). doi:10.1097/WNR.0b013e328346b138

    Article  Google Scholar 

  41. Effgen, G.B., Vogel III, E.W., Lynch, K.A., Lobel, A., Hue, C.D., Meaney, D.F., Bass, C.R., Morrison III, B.: Isolated primary blast alters neuronal function with minimal cell death in organotypic hippocampal slice cultures. J. Neurotrauma 31, 1202–1210 (2014). doi:10.1089/neu.2013.3227

    Article  Google Scholar 

  42. Effgen, G.B., Hue, C.D., Vogel III, E., Panzer, M.B., Meany, D.F., Bass, C.R., Morrison III, B.: A multiscale approach to blast neurotrauma modeling: Part II: Methodology for inducing blast injury to in vitro models. Front. Neurol. 3, 23 (2012). doi:10.3389/fneur.2012.00023

    Article  Google Scholar 

  43. Effgen, G.B., Ong, T., Nammalwar, S., Ortuño, A.I., Meaney, D.F., Bass, C.R., Morrison III, B.: Primary blast exposure increases hippocampal vulnerability to subsequent exposure: reducing long-term potentiation. J. Neurotrauma 33, 1901–1912 (2016). doi:10.1089/neu.2015.4327

    Article  Google Scholar 

  44. Hue, C.D., Cao, S., Haider, S.F., Vo, K.V., Effgen, G.B., Vogel III, E., Panzer, M.B., Bass, C.R., Meaney, D.F., Morrison III, B.: Blood-brain barrier dysfunction after primary blast injury in vitro. J. Neurotrauma 30, 1652–1663 (2013). doi:10.1089/neu.2012.2773

    Article  Google Scholar 

  45. Hue, C.D., Cao, S., Bass, C.R., Meaney, D.F., Morrison III, B.: Repeated primary blast injury causes delayed recovery, but not additive disruption, in an in vitro blood-brain barrier model. J. Neurotrauma 31, 951–960 (2014). doi:10.1089/neu.2013.3149

    Article  Google Scholar 

  46. Hue, C.D., Cho, F.S., Cao, S., Bass, C.R., Meaney, D.F., Morrison III, B.: Dexamethasone potentiates in vitro blood-brain recovery after primary blast injury by glucocorticoid receptor-mediated upregulation of ZO-1 tight junction protein. J. Cereb. Blood Flow Metab. 35, 1191–1198 (2015). doi:10.1038/jcbfm.2015.38

    Article  Google Scholar 

  47. Kane, M.J., Angoa-Perez, M., Francescutti, D.M., Sykes, C.E., Briggs, D.I., Leung, L.Y., Vandevord, P.J., Kuhn, D.M.: Altered gene expression in cultured microglia in response to simulated blast overpressure: Possible role of pulse duration. Neurosci. Lett. 522, 47–51 (2012). doi:10.1016/j.neulet.2012.06.012

    Article  Google Scholar 

  48. Leung, L.Y., Vandevord, P.J., Dal Cengio, A.L., Bir, C., Yang, K.H., King, A.I.: Blast related neurotrauma: A review of cellular injury. Mol. Cell Biomech. 5, 155–168 (2008). doi:10.3970/mcb.2008.005.155

    Google Scholar 

  49. Miller, A.P., Shah, A.S., Aperi, B.V., Budde, M.D., Pintar, F.A., Tarima, S., Kurpad, S.N., Stemper, B.D., Glavaski-Joksimovic, A.: Effects of blast overpressure on neurons and glial cells in rat organotypic hippocampal slice cultures. Front. Neurol. 6, 22 (2015). doi:10.3389/fneur.2015.00020

    Google Scholar 

  50. Panzer, M.B., Matthews, K.A., Yu, A.W., Morrison III, B., Meaney, D.F., Bass, C.R.: 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, 46 (2012). doi:10.3389/fneur.2012.00046

    Article  Google Scholar 

  51. Ravin, R., Blank, P.S., Busse, B., Ravin, N., Vira, S., Bezrukov, L., Waters, H., Guerrero-Cazares, H., Quinones-Hinojosa, A., Lee, P.R., Fields, R.D., Bezrukov, S.M., Zimmerberg, J.: Blast shockwaves propagate Ca\(^{2+}\) activity via purinergic astrocyte networks in human nervous system cells. Sci. Rep. 6, 25713 (2016). doi:10.1038/srep25713

    Article  Google Scholar 

  52. Ravin, R., Blank, P.S., Steinkamp, A., Rappaport, S.M., Ravin, N., Bezrukov, L., Guerrero-Cazares, H., Quinones-Hinojosa, A., Bezrukov, S.M., Zimmerberg, J.: Shear forces during blast, not abrupt changes in pressure alone, generate calcium activity in human brain cells. PLoS ONE 7(6), e39421 (2012). doi:10.1371/journal.pone.0039421

    Article  Google Scholar 

  53. Sawyer, T.W., Lee, J., Villanueva, M., Wang, Y., Nelson, P., Song, Y., Hennes, G., Fan, C., McLaws, L.: The effect of underwater blast on aggregating brain cell cultures. J. Neurotrauma 34, 517–528 (2017). doi:10.1089/neu.2016.4430

    Article  Google Scholar 

  54. Sawyer, T.W., Villanueva, M., Wang, Y., Ritzel, D.V., Josey, T., Nelson, P., Weiss, T., Song, Y., Vair, C., Fan, C.: Primary blast causes delayed effects without cell death in shell-encased brain cell aggregates. J. Neurotrauma (2017). doi:10.1089/neu.2016.4961

  55. VandeVord, P.J., Leung, L.Y., Hardy, W., Mason, M., Yang, K.H., King, A.I.: Up-regulation of reactivity and survival genes in astrocytes after exposure to short duration overpressure. Neurosci. Lett. 434, 247–252 (2008). doi:10.1016/j.neulet.2008.01.056

    Article  Google Scholar 

  56. Vogel III, E.W., Effgen, G.B., Patel, T.P., Meaney, D.F., Bass, C.R., Morrison III, B.: Isolated primary blast inhibits long-term potentiation in organotypic hippocampal slice cultures. J. Neurotrauma 33, 652–661 (2016). doi:10.1089/neu.2015.4045

    Article  Google Scholar 

  57. Zander, N.E., Piehler, T., Boggs, M.E., Banton, R., Benjamin, R.: In vitro studies of primary explosive blast loading on neurons. J. Neurosci. Res. 93, 1353–1363 (2015). doi:10.1002/jnr.23594

    Article  Google Scholar 

  58. Zander, N.E., Piehler, T., Banton, R., Boggs, M.: The effect of explosive blast loading on human neuroblastoma cells. Anal. Biochem. 504, 4–6 (2016). doi:10.1016/j.ab.2016.03.009

    Article  Google Scholar 

  59. Josey, T., Ritzel, D.V., Sawyer, T.W.: Development of a miniature double Pitot-static probe and its application to calibrating blast flow conditions. In: Proceedings of the 24th Military Aspects of Blast and Shock Symposium, Halifax, 18–23 Sept 2016

  60. Honegger, P.: Aggregating neural cell cultures. In: Current Protocols in Toxicology. Wiley, New York, Unit 12.9 (2003). doi:10.1002/0471140856.tx1209s15

  61. Honegger, P., Defaux, A., Monnet-Tschudi, F., Zurich, M.-G.: Preparation, maintenance, and use of serum-free aggregating brain cell cultures. In: Costa, L.G., et al. (eds.) In Vitro Neurotoxicology: Methods and Protocols, Methods in Molecular Biology, vol. 758. Springer, New York (2011). doi:10.1007/978-1-61779-170-3_6

    Chapter  Google Scholar 

  62. Sa Santos, S.S., Leite, S.B., Sonnewald, U., Carrondo, M.J.T., Alves, P.M.: Stirred vessel cultures of rat brain cells aggregates: Characterization of major metabolic pathways and cell population dynamics. J. Neurosci. Res. 85, 3386–3397 (2007). doi:10.1002/jnr.21409

    Article  Google Scholar 

  63. Lee, J.J., Rude, G.: Methodologies and gauges for intracranial pressure measurements. In: Proceedings of the Personal Armour Systems Symposium (PASS), Amsterdam, 19–23 Sept 2016

  64. Lu, J., Ng, K.C., Ling, G., Wu, J., Poon, D.J.F., Kan, E.M., Tan, M.H., Wu, Y.J., Li, P., Moochhala, S., Yap, E., Lee, L.K.H., Teo, M., Yeh, I.B., Sergio, D.M.B., Chua, F., Kumar, S.D., Ling, E.-A.: Effect of blast exposure on the brain structure and cognition in Macaca fascicularis. J. Neurotrauma 29, 1434–1454 (2012). doi:10.1089/neu.2010.1591

    Article  Google Scholar 

  65. Pun, P.B.L., Kan, E.M., Salim, A., Li, Z., Ng, K.C., Moochhala, S.M., Ling, E.-A., Tan, M.H., Lu, J.: Low level primary blast injury in rodent brain. Front. Neurol. 2, 19 (2011). doi:10.3389/fneur.2011.00019

    Article  Google Scholar 

  66. Rubovitch, V., Ten-Bosch, M., Zohar, O., Harrison, C.R., Tempel-Brami, C., Stein, E., Hoffer, B.J., Balaban, C.D., Schreiber, S., Chiu, W.-T., Pick, C.G.: A mouse model of blast-induced mild traumatic brain injury. Exp. Neurol. 232, 280–289 (2011). doi:10.1016/j.expneurol.2011.09.018

    Article  Google Scholar 

  67. Woods, A.M., Colsch, B., Jackson, S.N., Post, J., Baldwin, K., Roux, A., Hoffer, B., Cox, B.M., Hoffer, M., Rubovitch, V., Pick, C.G.: Gangliosides and ceramides change in a mouse model of blast induced traumatic brain injury. ACS Chem. Neurosci. 4, 594–600 (2013). doi:10.1021/cn300216h

    Article  Google Scholar 

  68. Säljö, S., Arrhén, F., Bolouri, H., Mayorga, M., Hamberger, A.: Neuropathology and pressure in the pig brain resulting from low-impulse noise exposure. J. Neurotrauma 25, 1397–1406 (2008). doi:10.1089/neu.2008.0602

    Article  Google Scholar 

  69. Courtney, M.W., Courtney, A.C.: Note: a table-top blast-driven shock tube. Rev. Sci. Instrum. 81, 1261031–3 (2010). doi:10.1063/1.3518970

    Article  Google Scholar 

  70. Kuehn, R., Simard, P.F., Driscoll, I., Keledjian, K., Ivanova, S., Tosun, C., Williams, A., Bochicchio, G., Gerzanich, V., Simard, J.M.: Rodent model of direct cranial injury. J. Neurotrauma 28, 2155–2169 (2011). doi:10.1089/neu.2010.1532

    Article  Google Scholar 

  71. Simard, J.M., Pampori, A., Keledjian, K., Tosun, C., Schwartzbauer, G., Ivanova, S., Gerzanich, V.: Exposure of the thorax to a sublethal blast wave causes a hydrodynamic pulse that leads to perivenular inflammation of the brain. J. Neurotrauma 31, 1292–1304 (2014). doi:10.1089/neu.2013.3016

    Article  Google Scholar 

  72. Heldt, S.A., Elberger, A.J., Deng, Y., Guley, N.H., Del Mar, N., Rogers, J., Choi, G.W., Ferrell, J., Rex, T.S., Honig, M.G., Reiner, A.: A novel closed-head model of mild traumatic brain injury caused by primary overpressure blast to the cranium produces sustained emotional deficits in mice. Front. Neurol. 5, 2 (2014). doi:10.3389/fneur.2014.00002

    Article  Google Scholar 

  73. Säljö, S., Bao, F., Haglid, K.G., Hansson, H.-A.: Blast exposure causes redistribution of phosphorylated neurofilament subunits in neurons of the adult rat brain. J. Neurotrauma 17, 719–726 (2000). doi:10.1089/089771500415454

    Article  Google Scholar 

  74. Risling, M., Davidsson, J.: Experimental animal models for studies on the mechanisms of blast induced neurotrauma. Front. Neurol. 3, 30 (2012). doi:10.3389/fneur.2012.00030

    Google Scholar 

  75. Risling, M., Plantman, S., Angeria, M., Rostami, E., Bellander, B.-M., Kirkegaard, M., Arborelius, U., Davidsson, J.: Mechanisms of blast induced brain injuries, experimental studies in rats. Neuroimage 54, S89–S97 (2011). doi:10.1016/j.neuroimage.2010.05.031

    Article  Google Scholar 

  76. Chavko, M., Watanabe, T., Adeeb, S., Lankasky, J., Ahlers, S.T., McCarron, R.M.: Relationship between orientation to a blast and pressure wave propagation inside the rat brain. J. Neurosci. Methods 195, 61–66 (2011). doi:10.1016/j.jneumeth.2010.11.019

    Article  Google Scholar 

  77. Garman, R.H., Jenkins, L.W., Switzer III, R.C., Bauman, R.A., Tong, L.C., Swauger, P.V., Parks, S.A., Ritzel, D.V., Dixon, C.E., Clark, R.S.B., Bayir, H., Kagan, V., Jackson, E.K., Kochanek, P.M.: Blast exposure in rats with body shielding is characterized primarily by diffuse axonal injury. J. Neurotrauma 28, 947–959 (2011). doi:10.1089/neu.2010.1540

    Article  Google Scholar 

  78. Reneer, D.V., Hisel, R.D., Hoffman, J.M., Kryscio, R.J., Lusk, B.T., Geddes, J.W.: A multi-mode shock tube for investigation of blast-induced traumatic injury. J. Neurotrauma 28, 95–104 (2011). doi:10.1089/neu.2010.1513

    Article  Google Scholar 

  79. Skotak, M., Wang, F., Alai, A., Holmberg, A., Harris, S., Switzer, R.C., Chandra, N.: Rat injury model under controlled field-relevant primary blast conditions: Acute response to a wide range of peak overpressures. J. Neurotrauma 30, 1147–1160 (2013). doi:10.1089/neu.2012.2652

    Article  Google Scholar 

  80. Tomkins, P., Tesiram, Y., Lerner, M., Gonzalez, L.P., Lightfoot, S., Rabb, C.H., Brackett, D.J.: Brain injury: Neuro-inflammation, cognitive deficit, and magnetic resonance imaging in a model of blast-induced traumatic brain injury. J. Neurotrauma 30, 1888–1897 (2013). doi:10.1089/neu.2012.2674

    Article  Google Scholar 

  81. VandeVord, P.J., Bolander, R., Sajja, V.S.S.S., Hay, K., Bir, C.A.: Mild neurotrauma indicates a range-specific pressure response to low level shock wave exposure. Ann. Biomed. Eng. 40, 227–236 (2012). doi:10.1007/s10439-011-0420-4

    Article  Google Scholar 

  82. Park, E., Gottleib, J.J., Cheung, B., Shek, P.N., Baker, A.J.: A model of low-level primary blast brain trauma results in cytoskeletal proteolysis and chronic functional impairment in the absence of lung barotrauma. J. Neurotrauma 28, 343–357 (2011). doi:10.1089/neu.2009.1050

    Article  Google Scholar 

  83. Svetlov, S.I., Prima, V., Kirk, D.R., Gutierrez, H., Curley, K.C., Hayes, R.L., Wang, K.K.W.: Morphologic and biochemical characterization of brain injury in a model of controlled blast overpressure exposure. J. Trauma 69, 795–804 (2010). doi:10.1097/TA.0b013e3181bbd885

    Article  Google Scholar 

  84. Svetlov, S.I., Prima, V., Glushakova, O., Svetlov, A., Kirk, D.R., Gutierrez, H., Serebruany, V.L., Curley, K.C., Wang, K.K.W., Hayes, R.L.: Neuro-glial and systemic mechanisms of pathological responses in rat models of primary blast overpressure compared to “composite” blast. Front. Neurol. 3, 15 (2012). doi:10.3389/fneur.2012.00015

    Article  Google Scholar 

  85. Kato, K., Fujimura, M., Nakagawa, A., Saito, A., Ohki, T., Takayama, K., Tominaga, T.: Pressure-dependent effect of shock waves on rat brain: Induction of neuronal apoptosis mediated by a caspase-dependent pathway. J. Neurosurg. 106, 667–676 (2007). doi:10.3171/jns.2007.106.4.667

    Article  Google Scholar 

  86. Alphonse, V.D., Salja, V.S.S.S., Kemper, A.R., Ritzel, D.V., Duma, S.M., VandeVord, P.J.: Membrane characteristics for biological blast overpressure testing using blast simulators. Biomed. Sci. Instrum. 50, 248–253 (2014)

    Google Scholar 

  87. Josey, T., Sawyer, T.W., Ritzel, D., Donahue, L.: High fidelity simulation of free-field blast-loading: the importance of dynamic pressure. In: Proceedings of the Personal Armour Systems Symposium (PASS), Amsterdam, 19–23 Sept 2016

  88. Diaz-Arrastia, R., Wang, K.K.W., Papa, L., Sorani, M.D., Yue, J.K., Puccio, A.M., McMahon, P.J., Inoue, T., Yuh, E.L., Lingsma, H.F., Maas, A.I.R., Valadka, A.B., Okonkwo, D.O., Manley, G.T., Casey, S.S., Cheong, M., Cooper, S.R., Dams-O’Connor, K., Gordon, W.A., Hricik, A.J., Menon, D.K., Mukherjee, P., Schnyer, D.M., Sinha, T.K., Vassar, M.J.: Acute biomarkers of traumatic brain injury: Relationship between plasma levels of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein. J. Neurotrauma 31, 19–25 (2014). doi:10.1089/neu.2013.3040

    Article  Google Scholar 

  89. Honda, M., Tsuruta, R., Kaneko, T., Kasaoka, S., Yagi, T., Todani, M., Fujita, M., Izumi, T., Maekawa, T.: Serum glial fibrillary acidic protein is a highly specific biomarker for traumatic brain injury in humans compared to S-100B and neuron-specific enolase. J. Trauma 69, 104–109 (2010). doi:10.1097/TA.0b013e3181bbd485

    Article  Google Scholar 

  90. Arun, P., Abu-Taleb, R., Oguntayo, S., Tanaka, M., Wang, Y., Valiyaveettil, M., Long, J.B., Zhang, Y., Nambiar, M.P.: Distinct patterns of expression of traumatic brain injury biomarkers after blast exposure: Role of compromised cell membrane integrity. Neurosci. Lett. 552, 87–91 (2013). doi:10.1016/j.neulet.2013.07.047

    Article  Google Scholar 

  91. Cernak, I., Ahmed, F.A.: A comparative analysis of blast-induced neurotrauma and blunt traumatic brain injury reveals significant differences in injury mechanisms. Med. Data Rev. 2, 297–304 (2010)

    Google Scholar 

  92. Cernak, I., Merkle, A.C., Koliatsos, V.E., Bilik, J.M., Luong, Q.T., Mahota, T.M., Xu, L., Slack, N., Windle, D., Ahmed, F.A.: The pathobiology of blast injuries and blast-induced neurotrauma as identified using a new experimental model of injury in mice. Neurobiol. Dis. 41, 538–551 (2011). doi:10.1016/j.nbd.2010.10.025

    Article  Google Scholar 

  93. Polivka Jr., J., Janku, F.: Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway. Pharmacol. Ther. 142, 164–175 (2014). doi:10.1016/j.pharmthera.2013.12.004

    Article  Google Scholar 

  94. Dienstmann, R., Rodon, J., Serra, V., Tabernero, J.: Picking the point of inhibition: a comparative review of PI3K/AKT/mTOR pathway inhibitors. Mol. Cancer Ther. 13, 1021–1031 (2014). doi:10.1158/1535-7163.MCT-13-0639

  95. Li, T., Wang, G.: Computer-aided targeting of the PI3K/AKT/mTOR pathway: toxicity reduction and therapeutic opportunity. Int. J. Mol. Sci. 15, 18856–18891 (2014). doi:10.3390/ijms151018856

    Article  Google Scholar 

  96. Ahn, J.-Y.: Neuroprotection signaling of nuclear Akt in neuronal cells. Exp. Neurobiol. 23, 200–206 (2014). doi:10.5607/en.2014.23.3.200

    Article  Google Scholar 

  97. Smith, G.A., Fearnley, G.W., Harrison, M.A., Tomlinson, D.C., Wheatcroft, S.B., Ponnambalam, S.: Vascular endothelial growth factor: Multitasking functionality in metabolism, health and disease. J. Inherit. Metab. Dis. 38, 753–763 (2015). doi:10.1007/s10545-015-9838-4

  98. Evans, I.: An overview of VEGF-mediated signal transduction. In: Fiedler, L. (ed.) VEGF Signaling: Methods and Protocols, Methods in Molecular Biology. Springer, New York (2015). doi:10.1007/978-1-4939-2917-7_7

    Google Scholar 

  99. Hohman, T.J., Bell, S.P., Jefferson, A.L.: The role of vascular endothelial growth factor in neurodegeneration and cognitive decline: Exploring interactions with biomarkers of Alzheimer disease. JAMA Neurol. 72, 520–529 (2015). doi:10.1001/jamaneurol.2014.4761

    Article  Google Scholar 

  100. Lange, C., Storkebaum, E., Ruiz de Almodóvar, C., Dewerchin, M., Carmeliet, P.: Vascular endothelial growth factor: A neurovascular target in neurological diseases. Nat. Rev. Neurol. 12, 439–454 (2016). doi:10.1038/nrneurol.2016.88

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to T. W. Sawyer.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Communicated by O. Petel and S. Ouellet.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sawyer, T.W., Josey, T., Wang, Y. et al. Investigations of primary blast-induced traumatic brain injury. Shock Waves 28, 85–99 (2018). https://doi.org/10.1007/s00193-017-0756-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00193-017-0756-2

Keywords

Navigation