Modeling methods in understanding and ameliorating central nervous system injury
Creators: name: Singh, Sagar
Publisher: name: No Publisher Supplied
Year: 2016

description: To improve the quality of life for victims of traumatic spinal cord and brain injury, a   better understanding of how microstructural mechanical behavior influences bulk tissue and vice   versa is necessary. Two aspects that warrant attention in this matter are primary injury and neural   electrode-tissue interactions. While their respective biomechanics are measurable at the   macroscopic level, it is difficult to measure microscopic deformations during injury in situ and in   vivo experimentally. To overcome this limitation, we develop experimentally validated   computational approaches to predict the multiscale translations involved in white matter tissue   injury, and probe-tissue interfaces.   In the first part of this dissertation, we developed approaches to model primary injury at   the axon level. First we developed 3-D axon kinematic models to infer axonal strain as a function   of tissue-level stretch. Embryonic chick spinal cord tissue was exposed to controlled stretch and   axon tortuosity and kinematics were characterized in 3-dimensions. We determined that greater   proportions of axons are predicted to behave with affine, composite-like kinematics. Next, we   identified and evaluated contactin-associated protein (Caspr) for use as a fiducial marker in   estimating axonal strain and axonal failure thresholds. Spinal cord tissue was exposed to   controlled stretch, and displacements of immunostained Caspr proteins were measured. Changes   in Caspr displacements reflected the applied macroscopic stretch directly at earlier stages of   development but this trend deviated with further development. This shift in trend correlated with   observations of axon failure at later stages of development, and we predicted axon failure   thresholds to decrease with development.   In the second part of this dissertation, we developed approaches to model multiscale   mechanics in neural probe and tissue interactions. Finite element simulations were developed   and experimentally validated to determine insertion and buckling forces for different coating and   probe designs. Parameter sweeps of these features determined that probe length and coating   thickness had the biggest impact on insertion forces. Next, we used the model to simulate the   probe-tissue interface in order to correlate interfacial stress and tissue strain to chronic injury.   Stress and strain predictions were made for a variety of probe designs and results were validated   with parallel experiments using agarose tissue phantoms. We correlated predictions to gliosis   through an in vitro model where astrocytes cultured in collagen gels were cast around a probe   and exposed to micromotion. We determined that probe stiffness has a greater effect on chronic   injury than size. We were also able to predict minimum strain thresholds for inducing astrocyte   activation.  The findings in this work help elucidate multiscale transfers in white matter injury and   probe-tissue interfaces. These results can be applied to the design of better preventative measures   for brain and spinal cord injury (sports and military equipment), as well as neural probes for   long-term signal acquisition/stimulation in brain-to-computer interfaces.