Session: 16-01-01: NSF-funded Research (Grad & Undergrad)

Paper Number: 77203

Start Time: Wednesday, 02:25 PM

77203 - Hyperelastic Effect of Oligodendrocyte 3d Connections to Axons in Brain White Matter 

Abstract: Numerical modeling of Traumatic brain injury (TBI) and central nervous system (CNS) extremities has sprung intense interest among researchers to depict deterministically and analyze the impact of axonal injuries. Finite element simulations leveraging non-linear hyper-elastic material models to approximate connections between oligodendrocytes and axons in an extracellular matrix (ECM) have emerged as prospective solutions. These solutions characterize the stress states and investigate the anticipated structural stiffness changes corresponding to parametrically varying oligodendrocyte-axon connections configurations. In the current study, one such novel finite element model (FEM) has been proposed to evaluate the mechanical response of axons embedded in ECM when subjected to tensile loads under purely non-affine kinematic boundary conditions. Ogden's hyper-elastic material model describes the axons and the ECM material characterizations. FEM leveraging the Ogden model is deployed to understand the impact of parametrically varying oligodendrocyte-axon tethering and analyze the influence of aging material characteristics on stress propagation.

In the proposed FEM, oligodendrocyte connections to axons use a spring-dashpot model approximation.  The tethering technique allows oligodendrocytes to wrap around the outer diameter of the axons at various locations, thereby facilitating parameterization of spatial contact definitions (one to five connections per axon), distance between the connection points, and vary stiffness of the connection hubs. The connection model mimics the tethering between oligodendrocytes and axons, facilitating inter-axonal bonding and creating a myelin sheath that insulates and supports axons in the brainstem. At first, 1) multiple oligodendrocytes arbitrarily tethered to the nearest axons FEM is analyzed for varying stiffnesses, and 2) a single oligodendrocyte tethered to all the axons at various locations FEM has been improved by adding two and four nodal oligodendrocyte connections per axons scenarios to complete existing submodel-2 FEM ensemble.  Results yielded from both submodels encompassed all parametrically varying scenarios and enabled comprehensive comparative analysis.  Next, both submodels' stress states and stiffness variations were analyzed by incorporating aging material characteristics in the axon FEM model.  Root mean square deviation (RMSD) was computed between stress-strain response plots for varying connections in the ensemble to depict trends in mechanical response and bending stresses. Axonal stiffness was found to rise with increasing tethering, indicating the role of oligodendrocytes in stress redistribution, and enhancing mechanical response.  In the second submodel, for same number of connections per axons, RMSD values increased as "K" (oligodendrocyte stiffness) values were set higher. RMSD calculations reveal that for a "K" value, submodel-2 yielded slightly stiffer models compared to submodel-1. Appearance of cyclic bending stresses in both submodels suggests risk of axonal damage accumulation and fatigue failure. Finally, stress state results for aging axon material, with varying stiffnesses and number of connections in FEM ensemble have also been discussed to demonstrate gradual softening of tissues.

Keywords: micromechanics, fatigue modeling, FEM, oligodendrocyte, TBI, axonal injury, CNS white matter, multi-scale simulation, hyper-elastic materials, Abaqus

Presenting Author: Mohit Agarwal Rutgers, The State University of New Jersey

Authors:

Mohit Agarwal Rutgers, The State University of New Jersey
Parameshwaran Pasupathy Rutgers, The State University of New Jersey
Assimina A. Pelegri Rutgers, The State University of New Jersey