Document Type : Full Research Paper

Authors

1 MSc. Biomedical Engineering-Biomechanics, Faculty of New Sciences and Technologies, University of Tehran, Tehran

2 Assistant Professor, Biomedical Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran

Abstract

Due to the importance of the brain and neurons, a vast area of research has been conducted in this field. However, due to the complexity of the neural behavior, each study investigated the functionality of neurons from one perspective such as electrophysiological, chemical, or mechanical perspective. In spite of the large number of research conducted on the brain injury topic, there is no study investigating the interaction of the mechanical and electrical characteristics of the neurons and its effect on the cell functionality. Understating the interaction between the mechanical and electrical properties of a neuron will have a substantial effect on treating neurological diseases such as traumatic brain injury and improving treatment methods such as ultrasound. As a result, there is a vital need to simulate the effect of mechanical forces on the electrophysiological behavior of a neuron. This study is one of the few attempts to achieve this goal by taking into account the mechanosensitivity of ion channels which affects the action potentials. Our proposed comprehensive model is based on power law equation (fractional dashpot) for mechanical modeling, Hodgkin Huxley (HH) equation for electrophysiological model and recent experiments for combination of these two equations. Based on the model, the calculated strain from the power law equation affects the activation and inactivation of ion channels. By changing the activation and inactivation variable in the HH equation, we can evaluate the effect of strain and mechanical stimulation on neural function. The results reveal neuron functions’ deficiency during neuron mechanical damage. As a result, action potential signal’s amplitude reduces. This reduction in amplitude of the action potential may be reversible or irreversible based on the amount of damage (plastic deformation).

Keywords

Main Subjects

[1]     T. Grevesse, B. E. Dabiri, K. K. Parker, and S. Gabriele, “Opposite rheological properties of neuronal microcompartments predict axonal vulnerability in brain injury.,” Sci. Rep., vol. 5, p. 9475, Mar. 2015.
[2]     Y. B. Lu et al., “Viscoelastic properties of individual glial cells and neurons in the CNS,” Proc. Natl. Acad. Sci. USA, vol. 103, pp. 17759–17764, 2006.
[3]     T. REEVES, L. PHILLIPS, and J. POVLISHOCK, “Myelinated and unmyelinated axons of the corpus callosum differ in vulnerability and functional recovery following traumatic brain injury,” Exp. Neurol., vol. 196, no. 1, pp. 126–137, Nov. 2005.
[4]     B. B. Bendlin et al., “Longitudinal changes in patients with traumatic brain injury assessed with diffusion-tensor and volumetric imaging,” Neuroimage, vol. 42, pp. 503–514, 2008.
[5]     C. L. Mac Donald, K. Dikranian, S. K. Song, P. V. Bayly, D. M. Holtzman, and D. L. Brody, “Detection of traumatic axonal injury with diffusion tensor imaging in a mouse model of traumatic brain injury,” Exp. Neurol., vol. 205, pp. 116–131, 2007.
[6]     D. H. Smith and D. F. Meaney, “Axonal Damage in Traumatic Brain Injury,” Neurosci., vol. 6, no. 6, pp. 483–495, Dec. 2000.
[7]     T. Rickett, S. Connell, J. Bastijanic, S. Hegde, and R. Shi, “Functional and mechanical evaluation of nerve stretch injury,” J. Med. Syst., vol. 35, no. 5, pp. 787–793, 2011.
[8]     R. Shi and J. Whitebone, “Conduction Deficits and Membrane Disruption of Spinal Cord Axons as a Function of Magnitude and Rate of Strain,” J. Neurophysiol., vol. 95, no. 6, 2006.
[9]     A. C. Bain and D. F. Meaney, “Tissue-level thresholds for axonal damage in an experimental model of central nervous system white matter injury.,” J. Biomech. Eng., vol. 122, no. 6, pp. 615–22, Dec. 2000.
[10] T. J. J. Dennerll, P. Lamoureux, R. E. E. Buxbaum, and S. R. R. Heidemann, “The cytomechanics of axonal elongation and retraction,” J. Cell Biol., vol. 109, no. 6 I, pp. 3073–3083, 1989.
[11] R. Bernal, P. A. Pullarkat, and F. Melo, “Mechanical properties of axons,” Phys. Rev. Lett., vol. 99, p. 18301, 2007.
[12] S. Kleiven, “Predictors for traumatic brain injuries evaluated through accident reconstructions.,” Stapp Car Crash J., vol. 51, pp. 81–114, Oct. 2007.
[13] R. M. Wright and K. T. Ramesh, “An axonal strain injury criterion for traumatic brain injury,” Biomech. Model. Mechanobiol., vol. 11, no. 1–2, pp. 245–260, Jan. 2012.
[14] A. Jérusalem, J. A. García-Grajales, A. Merchán-Pérez, and J. M. Peña, “A computational model coupling mechanics and electrophysiology in spinal cord injury,” Biomech. Model. Mechanobiol., vol. 13, no. 4, pp. 883–896, Aug. 2014.
[15] L. J. Ng et al., “A Mechanistic End-to-End Concussion Model That Translates Head Kinematics to Neurologic Injury,” Front. Neurol., vol. 8, p. 269, Jun. 2017.
[16] C. S. Drapaca, “An electromechanical model of neuronal dynamics using Hamilton’s principle.,” Front. Cell. Neurosci., vol. 9, p. 271, 2015.
[17] N. Bonakdar et al., “Mechanical plasticity of cells.,” Nat. Mater., vol. 15, no. 10, pp. 1090–4, Oct. 2016.
[18] D. Craiem and R. L. Magin, “Fractional order models of viscoelasticity as an alternative in the analysis of red blood cell (RBC) membrane mechanics.,” Phys. Biol., vol. 7, no. 1, p. 13001, Jan. 2010.
[19] “Creep Function of a Single Living Cell,” Biophys. J., vol. 88, no. 3, pp. 2224–2233, Mar. 2005.
[20] T. Heimburg and A. D. Jackson, “On soliton propagation in biomembranes and nerves.,” Proc. Natl. Acad. Sci. U. S. A., vol. 102, no. 28, pp. 9790–5, Jul. 2005.
[21] A. L. Hodgkin and A. F. Huxley, “A quantitative description of membrane current and its application to conduction and excitation in nerve,” J. Physiol., vol. 117, no. 4, pp. 500–544, Aug. 1952.
[22] C. Koch, Biophysics of computation : information processing in single neurons. Oxford University Press, 1999.
[23] J. A. Wang, W. Lin, T. Morris, U. Banderali, P. F. Juranka, and C. E. Morris, “Membrane trauma and Na+ leak from Nav1.6 channels,” Am. J. Physiol. - Cell Physiol., vol. 297, no. 4, 2009.
[24] V. Volman and L. J. Ng, “Computer Modeling of Mild Axonal Injury: Implications for Axonal Signal Transmission,” Neural Comput., vol. 25, no. 10, pp. 2646–2681, Oct. 2013.
[25] P. A. Boucher, B. Joós, and C. E. Morris, “Coupled left-shift of Nav channels: Modeling the Na+-loading and dysfunctional excitability of damaged axons,” J. Comput. Neurosci., vol. 33, no. 2, pp. 301–319, 2012.
[26] P.-A. Boucher, B. Joós, and C. E. Morris, “Coupled left-shift of Nav channels: modeling the Na+-loading and dysfunctional excitability of damaged axons,” J. Comput. Neurosci., vol. 33, no. 2, pp. 301–319, Oct. 2012.