The biophysics of neuron-astrocyte-vascular modeling in conditions of normalcy, Intracerebral Hemorrhagic (ICH) stroke and electrical stimulation

Date
2024-12-03
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract

Intracerebral Hemorrhagic (ICH) stroke is the second most common type of stroke, but the deadliest. Nearly 45% of patients succumb to complications, while the ones surviving suffer a high degree of morbidity and lose the previous quality of life. Neuromodulation has been used in past as a part of therapeutic regimens for post ischemic stroke (most common type of stroke) rehabilitation during the chronic stages. The idea of neuromodulation as a rehabilitation technique has been not formally studied from the first principles for ICH strokes whose outcomes are way more severe than ischemia. While our experimental work focuses on understanding whether neuromodulation can be applied in a practical setting of ICH during the acute phase to control outcome of the patient, this project explores the theoretical underpinnings of the effect of neuromodulation at a cellular systemic level of neuron-astrocyte-vascular system in the normal and acute conditions post ICH. We improvise the Hodgkin-Huxley neuron model to incorporate a presynaptic neuron, calcium transients in a neuron, the tripartite synapse along with the astrocytes, astrocytic calcium signaling, the post synaptic neuron, the cerebral blood flow as well as the oxygen and energy consumption dynamics. We simulate the various biochemical pathways that set in during the acute phase post ICH and implement electrical stimulation both in the normal and post stroke settings. The goal of this work is to understand qualitatively, the effects of electrical stimulation paradigms as a therapeutic strategy by analysing a set of non-linear Ordinary Differential Equations(ODEs). This is the first work of its kind, wherein electrical stimulation has been studied in such an elaborate setting incorporating not only the biophysics but also the bioenergetic effects of neurostimulation. The solution for the ODEs consists of traces and limit cycles, which exhibit the behaviour of different components under normal conditions, during stroke and during electrical stimulation. From these, it is safe to say that we get a closer look at the effects of various electrical neuromodulation paradigms under the given assumptions. This will be used to look into the gaps of theoretical understanding of such complex phenomena, paving the way for better future modeling of neurodegenerative diseases and various treatments for it.

Description
Degree
Master of Science
Type
Thesis
Keywords
biophysics, neuromodulation, nonlinear system dynamics, Ordinary Differential Equations, Systems analysis, stroke.
Citation
Has part(s)
Forms part of
Published Version
Rights
Link to license
Citable link to this page