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Axonal Varicosity Leading to Combined Effect of Stretching and Swelling on Action Potential Transmission: A Computational Study

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Abstract

Neurons are prone to deformations as a result of the shear effect between the grey and white matters caused by the rapid and sudden movement of the brain tissue during an event of a mechanical impact or neurodegenerative diseases. These structural damages are significantly prominent in the causation of axonal injuries which come in the form of stretching primarily and consequently followed by local swelling as a secondary effect. The microstructural alterations, which are brought about as a result of these physical distortions, have a significant impact on the electrophysiological performance of the neuron cells. The objective of our research was to examine the neural activity in response to the simultaneous impact of swelling and stretching resulting from an altered morphology referred to as varicosity. Our hypothesis postulates that the neuron is able to sustain its signal conduction capacities up to a specific threshold, following exposure to mechanical trauma, and experiences a loss of electrophysiological functionality afterwards upon reaching the critical threshold. Therefore, the aim of our study has been to examine the characteristics of action potential signals within a stretch-induced swelled segment of the axon using computational models aimed at imitating the electrical activity in neuronal cells. The simulations were structured according to the premise that the stretch-induced swelling site possesses ion channels that are vulnerable to mechanical damage, hence influencing the electrophysiology of the transmitted signals. The simulations were conducted to examine the effects of different swelling radii on mechanical strains of fluctuating magnitudes. Thus, we have obtained that the minimum threshold for the applied strain to be \(17\%\) to cause alterations in the AP signal transmission through an unmyelinated stretched-swelled axon. Notwithstanding this comprehension, further investigation has been required to examine the impact of higher magnitudes of strain rate changes on the performance of ion channels. In summary, the utilization of numerical simulations in conjunction with the models facilitated our ability to predict the damage threshold for a neuron cell by analyzing the extent of axonal electrophysiological deficits in response to the injury sustained at the cellular level.

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Data availability

The data supporting this study's findings can be requested from the corresponding author, [Ashfaq Adnan].

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Acknowledgements

This material is based upon research supported by the PANTHER program (URL: https://www.panther.engr.wisc.edu/; Director: Dr. Christian Franck, University of Wisconsin – Madison) through the U.S. Office of Naval Research (ONR) (award number: N00014-21-1-2855(0000001556); Program Director: Dr. Timothy Bentley). The authors would like to acknowledge the High-Performance Computing Modernization Program (HPCMP) by the U.S. Department of Defense (DOD) for providing the computational resources which contributed to achieving the outcomes reported in this study.

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  1. Department of Mechanical and Aerospace Engineering, University of Texas at Arlington, Arlington, TX, 76019, USA

    Md Navid Imtiaz Rifat & Ashfaq Adnan

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Rifat, M.N.I., Adnan, A. Axonal Varicosity Leading to Combined Effect of Stretching and Swelling on Action Potential Transmission: A Computational Study. Multiscale Sci. Eng. (2024). https://doi.org/10.1007/s42493-024-00112-y

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