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Biomechanics of Brain Injury: Looking to the Future

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Accidental Injury

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Abstract

In this chapter, we review the state of the field in understanding how the cellular components of the brain and spinal cord respond to the biomechanical loading that occurs at the moment of traumatic injury. Several other recent reviews can be collected and reviewed in their own right for this purpose (Kumaria A, Tolias CM, Br J Neurosurg 22(2):200–206, 2008; Morrison B 3rd, Elkin BS, Dolle JP, Yarmush ML, Annu Rev Biomed Eng 13:91–126, 2011; Chen YC, Smith DH, Meaney DF, J Neurotrauma 26(6):861–876, 2009; LaPlaca MC, Simon CM, Prado GR, Cullen DK, Prog Brain Res 161:13–26, 2007). Rather, we intend to provide a broad overview of the basic principles that led to our current understanding of how cells in the nervous system respond to mechanical force. We also point out critical emerging areas in this discipline as we move from molecules, genes, and cells to circuit, behavior and degenerative disease. Our holistic objective is bringing a mechanistic understanding of how mechanotransmission in the CNS can shape the neurobehavioral response of the organism after traumatic CNS injury.

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References

  1. Kumaria A, Tolias CM (2008) In vitro models of neurotrauma. Br J Neurosurg 22(2):200–206. doi:10.1080/02688690701772413

    Article  CAS  PubMed  Google Scholar 

  2. Morrison B 3rd, Elkin BS, Dolle JP, Yarmush ML (2011) In vitro models of traumatic brain injury. Annu Rev Biomed Eng 13:91–126. doi:10.1146/annurev-bioeng-071910-124706

    Article  CAS  PubMed  Google Scholar 

  3. Chen YC, Smith DH, Meaney DF (2009) In-vitro approaches for studying blast-induced traumatic brain injury. J Neurotrauma 26(6):861–876. doi:10.1089/neu.2008.0645

    Article  PubMed Central  PubMed  Google Scholar 

  4. LaPlaca MC, Simon CM, Prado GR, Cullen DK (2007) CNS injury biomechanics and experimental models. Prog Brain Res 161:13–26. doi:10.1016/S0079-6123(06)61002-9

    Article  CAS  PubMed  Google Scholar 

  5. Sundaramurthy A, Alai A, Ganpule S, Holmberg A, Plougonven E, Chandra N (2012) Blast-induced biomechanical loading of the rat: an experimental and anatomically accurate computational blast injury model. J Neurotrauma. doi:10.1089/neu.2012.2413

    PubMed  Google Scholar 

  6. Cloots RJ, van Dommelen JA, Kleiven S, Geers MG (2012) Multi-scale mechanics of traumatic brain injury: predicting axonal strains from head loads. Biomech Model Mechanobiol. doi:10.1007/s10237-012-0387-6

    PubMed  Google Scholar 

  7. Panzer MB, Myers BS, Capehart BP, Bass CR (2012) Development of a finite element model for blast brain injury and the effects of CSF cavitation. Ann Biomed Eng. doi:10.1007/s10439-012-0519-2

    Google Scholar 

  8. Coats B, Eucker SA, Sullivan S, Margulies SS (2012) Finite element model predictions of intracranial hemorrhage from non-impact, rapid head rotations in the piglet. Int J Dev Neurosci 30(3):191–200. doi:10.1016/j.ijdevneu.2011.12.009

    Article  PubMed Central  PubMed  Google Scholar 

  9. Lamy M, Baumgartner D, Willinger R, Yoganandan N, Stemper BD (2011) Study of mild traumatic brain injuries using experiments and finite element modeling. Ann Adv Automot Med. Annual Scientific Conference Association for the Advancement of Automotive Medicine Association for the Advancement of Automotive Medicine Scientific Conference 55:125–135

    Google Scholar 

  10. Chatelin S, Deck C, Renard F, Kremer S, Heinrich C, Armspach JP, Willinger R (2011) Computation of axonal elongation in head trauma finite element simulation. J Mech Behav Biomed Mater 4(8):1905–1919. doi:10.1016/j.jmbbm.2011.06.007

    Article  PubMed  Google Scholar 

  11. Kimpara H, Iwamoto M (2012) Mild traumatic brain injury predictors based on angular accelerations during impacts. Ann Biomed Eng 40(1):114–126. doi:10.1007/s10439-011-0414-2

    Article  PubMed  Google Scholar 

  12. Zhu F, Mao H, Dal Cengio Leonardi A, Wagner C, Chou C, Jin X, Bir C, Vandevord P, Yang KH, King AI (2010) Development of an FE model of the rat head subjected to air shock loading. Stapp Car Crash J 54:211–225

    CAS  PubMed  Google Scholar 

  13. Nyein MK, Jason AM, Yu L, Pita CM, Joannopoulos JD, Moore DF, Radovitzky RA (2010) In silico investigation of intracranial blast mitigation with relevance to military traumatic brain injury. Proc Natl Acad Sci U S A 107(48):20703–20708. doi:10.1073/pnas.1014786107

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Ho J, Kleiven S (2009) Can sulci protect the brain from traumatic injury? J Biomech 42(13):2074–2080. doi:10.1016/j.jbiomech.2009.06.051

    Article  PubMed  Google Scholar 

  15. King AI, Ruan JS, Zhou C, Hardy WN, Khalil TB (1995) Recent advances in biomechanics of brain injury research: a review. J Neurotrauma 12(4):651–658

    Article  CAS  PubMed  Google Scholar 

  16. Voo K, Kumaresan S, Pintar FA, Yoganandan N, Sances A Jr (1996) Finite-element models of the human head. Med Biol Eng Comput 34(5):375–381

    Article  CAS  PubMed  Google Scholar 

  17. Cohen AS, Pfister BJ, Schwarzbach E, Grady MS, Goforth PB, Satin LS (2007) Injury-induced alterations in CNS electrophysiology. Prog Brain Res 161:143–169. doi:10.1016/S0079-6123(06)61010-8

    Article  CAS  PubMed  Google Scholar 

  18. Lusardi TA, Wolf JA, Putt ME, Smith DH, Meaney DF (2004) Effect of acute calcium influx after mechanical stretch injury in vitro on the viability of hippocampal neurons. J Neurotrauma 21(1):61–72. doi:10.1089/089771504772695959

    Article  PubMed  Google Scholar 

  19. Geddes DM, LaPlaca MC, Cargill RS 2nd (2003) Susceptibility of hippocampal neurons to mechanically induced injury. Exp Neurol 184(1):420–427

    Article  CAS  PubMed  Google Scholar 

  20. Tavalin SJ, Ellis EF, Satin LS (1995) Mechanical perturbation of cultured cortical neurons reveals a stretch-induced delayed depolarization. J Neurophysiol 74(6):2767–2773

    CAS  PubMed  Google Scholar 

  21. LaPlaca MC, Thibault LE (1998) Dynamic mechanical deformation of neurons triggers an acute calcium response and cell injury involving the N-methyl-D-aspartate glutamate receptor. J Neurosci Res 52(2):220–229

    Article  CAS  PubMed  Google Scholar 

  22. Cargill RS 2nd, Thibault LE (1996) Acute alterations in [Ca2+]i in NG108-15 cells subjected to high strain rate deformation and chemical hypoxia: an in vitro model for neural trauma. J Neurotrauma 13(7):395–407

    Article  PubMed  Google Scholar 

  23. McKinney JS, Willoughby KA, Liang S, Ellis EF (1996) Stretch-induced injury of cultured neuronal, glial, and endothelial cells. Effect of polyethylene glycol-conjugated superoxide dismutase. Stroke 27(5):934–940

    Article  CAS  PubMed  Google Scholar 

  24. Smith DH, Wolf JA, Lusardi TA, Lee VM, Meaney DF (1999) High tolerance and delayed elastic response of cultured axons to dynamic stretch injury. J Neurosci 19(11):4263–4269

    CAS  PubMed  Google Scholar 

  25. Lusardi TA, Rangan J, Sun D, Smith DH, Meaney DF (2004) A device to study the initiation and propagation of calcium transients in cultured neurons after mechanical stretch. Ann Biomed Eng 32(11):1546–1558

    Article  PubMed  Google Scholar 

  26. Morrison B 3rd, Meaney DF, McIntosh TK (1998) Mechanical characterization of an in vitro device designed to quantitatively injure living brain tissue. Ann Biomed Eng 26(3):381–390

    Article  PubMed  Google Scholar 

  27. Morrison B 3rd, Cater HL, Benham CD, Sundstrom LE (2006) An in vitro model of traumatic brain injury utilising two-dimensional stretch of organotypic hippocampal slice cultures. J Neurosci Methods 150(2):192–201. doi:10.1016/j.jneumeth.2005.06.014

    Article  PubMed  Google Scholar 

  28. Meaney DF (2003) Relationship between structural modeling and hyperelastic material behavior: application to CNS white matter. Biomech Model Mechanobiol 1(4):279–293. doi:10.1007/s10237-002-0020-1

    Article  CAS  PubMed  Google Scholar 

  29. Karami G, Grundman N, Abolfathi N, Naik A, Ziejewski M (2009) A micromechanical hyperelastic modeling of brain white matter under large deformation. J Mech Behav Biomed Mater 2(3):243–254. doi:10.1016/j.jmbbm.2008.08.003

    Article  CAS  PubMed  Google Scholar 

  30. Bain AC, Shreiber DI, Meaney DF (2003) Modeling of microstructural kinematics during simple elongation of central nervous system tissue. J Biomech Eng 125(6):798–804

    Article  PubMed  Google Scholar 

  31. Pan Y, Shreiber DI, Pelegri AA (2011) A transition model for finite element simulation of kinematics of central nervous system white matter. IEEE Trans Biomed Eng 58(12):3443–3446. doi:10.1109/TBME.2011.2163189

    Article  PubMed  Google Scholar 

  32. Cohen TS, Smith AW, Massouros PG, Bayly PV, Shen AQ, Genin GM (2008) Inelastic behavior in repeated shearing of bovine white matter. J Biomech Eng 130(4):044504. doi:10.1115/1.2939290

    Article  PubMed Central  PubMed  Google Scholar 

  33. LaPlaca MC, Cullen DK, McLoughlin JJ, Cargill RS 2nd (2005) High rate shear strain of three-dimensional neural cell cultures: a new in vitro traumatic brain injury model. J Biomech 38(5):1093–1105. doi:10.1016/j.jbiomech.2004.05.032

    Article  PubMed  Google Scholar 

  34. LaPlaca MC, Thibault LE (1997) An in vitro traumatic injury model to examine the response of neurons to a hydrodynamically-induced deformation. Ann Biomed Eng 25(4):665–677

    Article  CAS  PubMed  Google Scholar 

  35. Prado GR, Ross JD, DeWeerth SP, LaPlaca MC (2005) Mechanical trauma induces immediate changes in neuronal network activity. J Neural Eng 2(4):148–158. doi:10.1088/1741-2560/2/4/011

    Article  PubMed  Google Scholar 

  36. Murphy EJ, Horrocks LA (1993) A model for compression trauma: pressure-induced injury in cell cultures. J Neurotrauma 10(4):431–444

    Article  CAS  PubMed  Google Scholar 

  37. Bell GI (1978) Models for the specific adhesion of cells to cells. Science 200(4342):618–627

    Article  CAS  PubMed  Google Scholar 

  38. Paoletti P, Ascher P (1994) Mechanosensitivity of NMDA receptors in cultured mouse central neurons. Neuron 13(3):645–655

    Article  CAS  PubMed  Google Scholar 

  39. Zhang L, Rzigalinski BA, Ellis EF, Satin LS (1996) Reduction of voltage-dependent Mg2+ blockade of NMDA current in mechanically injured neurons. Science 274(5294):1921–1923

    Article  CAS  PubMed  Google Scholar 

  40. Kloda A, Lua L, Hall R, Adams DJ, Martinac B (2007) Liposome reconstitution and modulation of recombinant N-methyl-D-aspartate receptor channels by membrane stretch. Proc Natl Acad Sci U S A 104(5):1540–1545. doi:10.1073/pnas.0609649104

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Singh P, Doshi S, Spaethling JM, Hockenberry AJ, Patel TP, Geddes-Klein DM, Lynch DR, Meaney DF (2012) N-methyl-D-aspartate receptor mechanosensitivity is governed by C terminus of NR2B subunit. J Biol Chem 287(6):4348–4359. doi:10.1074/jbc.M111.253740

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. DeRidder MN, Simon MJ, Siman R, Auberson YP, Raghupathi R, Meaney DF (2006) Traumatic mechanical injury to the hippocampus in vitro causes regional caspase-3 and calpain activation that is influenced by NMDA receptor subunit composition. Neurobiol Dis 22(1):165–176. doi:10.1016/j.nbd.2005.10.011

    Article  CAS  PubMed  Google Scholar 

  43. von Reyn CR, Spaethling JM, Mesfin MN, Ma M, Neumar RW, Smith DH, Siman R, Meaney DF (2009) Calpain mediates proteolysis of the voltage-gated sodium channel alpha-subunit. J Neurosci 29(33):10350–10356. doi:10.1523/JNEUROSCI.2339-09.2009

    Article  Google Scholar 

  44. Iwata A, Stys PK, Wolf JA, Chen XH, Taylor AG, Meaney DF, Smith DH (2004) Traumatic axonal injury induces proteolytic cleavage of the voltage-gated sodium channels modulated by tetrodotoxin and protease inhibitors. J Neurosci 24(19):4605–4613. doi:10.1523/JNEUROSCI.0515-03.2004

    Article  CAS  PubMed  Google Scholar 

  45. Wolf JA, Stys PK, Lusardi T, Meaney D, Smith DH (2001) Traumatic axonal injury induces calcium influx modulated by tetrodotoxin-sensitive sodium channels. J Neurosci 21(6):1923–1930

    CAS  PubMed  Google Scholar 

  46. von Reyn CR, Mott RE, Siman R, Smith DH, Meaney DF (2012) Mechanisms of calpain mediated proteolysis of voltage gated sodium channel alpha-subunits following in vitro dynamic stretch injury. J Neurochem 121(5):793–805. doi:10.1111/j.1471-4159.2012.07735.x

    Article  Google Scholar 

  47. Goforth PB, Ellis EF, Satin LS (1999) Enhancement of AMPA-mediated current after traumatic injury in cortical neurons. J Neurosci 19(17):7367–7374

    CAS  PubMed  Google Scholar 

  48. Goforth PB, Ellis EF, Satin LS (2004) Mechanical injury modulates AMPA receptor kinetics via an NMDA receptor-dependent pathway. J Neurotrauma 21(6):719–732. doi:10.1089/0897715041269704

    Article  PubMed  Google Scholar 

  49. Kao CQ, Goforth PB, Ellis EF, Satin LS (2004) Potentiation of GABA(A) currents after mechanical injury of cortical neurons. J Neurotrauma 21(3):259–270. doi:10.1089/089771504322972059

    Article  PubMed  Google Scholar 

  50. Charles AC, Merrill JE, Dirksen ER, Sanderson MJ (1991) Intercellular signaling in glial cells: calcium waves and oscillations in response to mechanical stimulation and glutamate. Neuron 6(6):983–992

    Article  CAS  PubMed  Google Scholar 

  51. Geddes DM, Cargill RS 2nd (2001) An in vitro model of neural trauma: device characterization and calcium response to mechanical stretch. J Biomech Eng 123(3):247–255

    Article  CAS  PubMed  Google Scholar 

  52. Elkin BS, Morrison B 3rd (2007) Region-specific tolerance criteria for the living brain. Stapp Car Crash J 51:127–138

    PubMed  Google Scholar 

  53. Cater HL, Sundstrom LE, Morrison B 3rd (2006) Temporal development of hippocampal cell death is dependent on tissue strain but not strain rate. J Biomech 39(15):2810–2818. doi:10.1016/j.jbiomech.2005.09.023

    Article  PubMed  Google Scholar 

  54. Patel TP, Ventre SC, Meaney DF (2012) Dynamic changes in neural circuit topology following mild mechanical injury in vitro. Ann Biomed Eng 40(1):23–36. doi:10.1007/s10439-011-0390-6

    Article  PubMed  Google Scholar 

  55. Soriano J, Rodriguez Martinez M, Tlusty T, Moses E (2008) Development of input connections in neural cultures. Proc Natl Acad Sci U S A 105(37):13758–13763. doi:10.1073/pnas.0707492105

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. Bernstein JG, Garrity PA, Boyden ES (2012) Optogenetics and thermogenetics: technologies for controlling the activity of targeted cells within intact neural circuits. Curr Opin Neurobiol 22(1):61–71. doi:10.1016/j.conb.2011.10.023

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Franks KM, Bartol TM Jr, Sejnowski TJ (2002) A Monte Carlo model reveals independent signaling at central glutamatergic synapses. Biophys J 83(5):2333–2348. doi:10.1016/S0006-3495(02)75248-X

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Franks KM, Stevens CF, Sejnowski TJ (2003) Independent sources of quantal variability at single glutamatergic synapses. J Neurosci 23(8):3186–3195

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Santucci DM, Raghavachari S (2008) The effects of NR2 subunit-dependent NMDA receptor kinetics on synaptic transmission and CaMKII activation. PLoS Comput Biol 4(10):e1000208. doi:10.1371/journal.pcbi.1000208

    Article  PubMed Central  PubMed  Google Scholar 

  60. Faas GC, Raghavachari S, Lisman JE, Mody I (2011) Calmodulin as a direct detector of Ca2+ signals. Nat Neurosci 14(3):301–304. doi:10.1038/nn.2746

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Nadkarni S, Bartol TM, Sejnowski TJ, Levine H (2010) Modelling vesicular release at hippocampal synapses. PLoS Comput Biol 6(11):e1000983. doi:10.1371/journal.pcbi.1000983

    Article  PubMed Central  PubMed  Google Scholar 

  62. Volman V, Levine H, Ben-Jacob E, Sejnowski TJ (2009) Locally balanced dendritic integration by short-term synaptic plasticity and active dendritic conductances. J Neurophysiol 102(6):3234–3250. doi:10.1152/jn.00260.2009

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  63. Keller DX, Franks KM, Bartol TM Jr, Sejnowski TJ (2008) Calmodulin activation by calcium transients in the postsynaptic density of dendritic spines. PLoS One 3(4):e2045. doi:10.1371/journal.pone.0002045

    Article  PubMed Central  PubMed  Google Scholar 

  64. Volpicelli-Daley LA, Luk KC, Patel TP, Tanik SA, Riddle DM, Stieber A, Meaney DF, Trojanowski JQ, Lee VM (2011) Exogenous alpha-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron 72(1):57–71. doi:10.1016/j.neuron.2011.08.033

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Departments of Bioengineering and Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA

    David F. Meaney Ph.D.

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  1. David F. Meaney Ph.D.
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Correspondence to David F. Meaney Ph.D. .

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Editors and Affiliations

  1. Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA

    Narayan Yoganandan

  2. School of Medicine, University of California at San Diego, San Diego, USA

    Alan M. Nahum

  3. Tandelta Inc., Ann Arbor, USA

    John W. Melvin

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Meaney, D.F. (2015). Biomechanics of Brain Injury: Looking to the Future. In: Yoganandan, N., Nahum, A., Melvin, J. (eds) Accidental Injury. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1732-7_10

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