Abstract for: Modeling long-term dynamic effects of brain injury on biological mechanisms of potential Parkinson’s disease
Parkinson’s disease (PD), the second most common neurodegenerative disorder affecting over ten million individuals worldwide, is a multifactorial disease influenced by several biological mechanisms and environmental risk factors. Complex interactions controlled by feedback relationships between key variables of neuroinflammation, oxidative damage, mitochondria, protein accumulation, and neuron sub-systems are at the center of the brain. While some lifestyle elements reduce vulnerability, head trauma greatly raises the risk for PD. Trauma-induced neuroinflammation is the most prominent short-term consequence, and due to intricate structure of brain, multiple variables are affected in long-term. To study those long-term impacts of brain injury on potential PD progression, we constructed an individual-level system dynamics model of a specific brain region where dopamine-producing neurons reside. After obtaining the dynamics of healthy aging, various injury scenarios are investigated to see whether healthy individuals would exhibit PD-like behaviors. Then, possible lifestyle factors such as healthy diet and exercise are tested on both healthy and PD-prone people. Using available qualitative and quantitative data, the model is structurally and behaviorally validated and scenario experiments are carried out.