The Neuronal Microenvironment

Author : Debabrata Auddya
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (145 download)

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Download or read book Multiphysics Modeling of Deformation in Biomembranes and the Neuronal Microenvironment, with Application to Traumatic Brain Injury written by Debabrata Auddya and published by . This book was released on 2024 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Traumatic Brain Injury (TBI) is a progressively common pathological condition worldwide caused due to concussion, impact or blast to the brain. Existing challenges in TBI detection and diagnosis are partly a result of the rich microstructural complexity of the brain and the multiscale heterogeneity of the cerebral architecture. During an injury, the brain gets exposed to significant loads which fall within the pathological spectrum. Neurons and neuron clusters, which are the functional and structural units of the brain, in turn experience this mechanical strain/stress leading to a wide range of morphological and biochemical abnormalities. Due to the inherent challenges in predicting and diagnosing these loading and injury conditions, there is a growing interest in computationally modeling the neurons, and their structural and functional units. However, current coarse-scale modeling and reduced representation of the underlying sub-neuronal structures often fail to render a rich spatio-temporal representation of neuronal mechanics and subsequently capturing neuronal injury. To address these limitations, we present continuum-scale computational frameworks for modeling the neuronal microenvironment and neuron clusters. We categorize this study into two aspects: biological membranes and the neuronal microenvironment.The significance of membranes in neuronal physiology is widely acknowledged due to their crucial roles in facilitating both ionic transmission and the transport of nutrients. In order to understand the morphological modifications which biomembranes undergo to enable critical biological processes, we develop a computational framework. This numerical methodology takes into account Kirchhoff Love thin shell kinematics, Helfrich energy representation of the curvature energy and the framework of Isogeometrical Analysis to model three dimensional representations of membranes. Unlike previous axisymmetric considerations, our model admits asymmetric and higher order, lower energy modes of deformation which are fundamental morphological adaptations that lipid bilayers seem to undergo. In the following chapters, we present a detailed description of the neuronal microenvironment and model various mechanical and chemical metrics of injury. Initially, we present a continuum-scale computational framework for modeling the neuronal microstructure and neuronal clusters. We capture viscoelastic behaviour of the sub-neuronal proteins which provide structural and functional integrity to the neurons using representative mechanical networks. A multi-scale approach of modeling deformation of a cluster of neurons is constructed in which local sub-neuronal strain-stress metrics are estimated under various global neuronal cluster loading conditions. In the final part of this work, we demonstrate a chemical basis of injury in which the pathological degradation of the neuronal microenvironment is considered. During a concussion or impact, beyond the initial mechanical injury (primary injury), a series of subsequent downstream pathways are set in motion, initiating a cascade of pathological biochemical processes. We have modeled some of these potential early stage (before the onset of any immune response) biochemical processes by simulating the spatio-temporal evolution of the relevant molecular biomarkers. These biomarkers are numerically modeled as coupled reaction-diffusion species that are modulated by mechanical strain/stress. This results in a comprehensive numerical framework for capturing the mechano-chemical multiphysics underlying neuronal injury, and also provides deeper insights into the spatio-temporal localization of the the mechanical metrics and the underlying biomarkers. A key highlight of this framework is the ability to obtain a computational injury curve that captures injury sensitivity of the neuronal microenvironment to rate dependent mechanical loading, and this is demonstrated using some initial (coarse) estimates of the injury envelope.