An isolated single myelinated nerve fiber model for the biomechanics of axonal injury
A unique, myelinated nerve model was developed for the study of traumatic neural injury and the biomechanical characterization of a single fiber. The dynamic loading conditions applied to the fiber were chosen to simulate in vivo strains and strain rates that result in axonal injury in animal models of head injury. An experimental system was designed and built to apply uniaxial displacements with rise times under 10 milliseconds and to measure dynamic force. The complex, composite structure of the myelinated nerve was reflected in the biomechanical response to elongation. Myelinated axons behave as viscoelastic solids that exhibit relaxation over milliseconds. Force strain curves were nonlinear and distinctly rate-dependent when comparing traumatic strain rates to lower, physiological rates. Fibers failed in the internodal region rather than at the unmyelinated node of Ranvier. Quasi-static elongation commonly resulted in nonuniform strains and plastic deformation. Possible mechanical contributions of myelinated axon components are explored. The intracellular free calcium concentration was measured ratiometrically using the calcium-sensitive fluorescent dye, fura-2. Following dynamic elongation, the calcium concentration increased immediately and peaked, typically within 30 seconds, at 50-1000% above pre-injury levels. In some cases, the calcium rise continued during the entire measurement period, while in others, the stretch-induced increase in ionic calcium was followed by a recovery toward pre-injury levels. Implications of this functional response to deformation and possible mechanisms for stretch-induced calcium transients are discussed. A constitutive relation for isolated single fibers was formulated from quasi-linear viscoelastic theory, disregarding local variations in mechanical properties and loading conditions. A lumped parameter nonlinear viscoelastic model was then developed to illustrate that recruitment of components within a composite results in nonuniform strains among components. Strain of the membrane component is postulated to result in local membrane 'failure' or pore formation. The hypothesis of strain-induced membrane pores is supported by similarities between stretch-induced conductance increases and conductance changes due to experimental membrane poration. Pore theory is suggested for modeling the hindered diffusion of ions through cell membrane pores with radii dependent upon strain, strain rate and time.
Saatman, Kathryn Eileen, "An isolated single myelinated nerve fiber model for the biomechanics of axonal injury" (1993). Dissertations available from ProQuest. AAI9413902.