Pathological Dynamics in a Neuron/Astrocyte Network Model

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Cerebral ischemic stroke is the third leading cause of death in the United States, trailing only cancer and heart disease. Despite the urgent need, mechanisms underlying brain injuries during stroke remain largely unknown and current therapeutic strategies to combat stroke have been largely unsuccessful. This project will develop a detailed mathematical model, which will be used to identify those mechanisms and processes that play a decisive role in the generation of ischemic-like conditions. Calcium signaling and energy production play a critical role in many cellular processes and have been implicated in a wide range of neurological diseases, including Parkinson's, Alzheimer's, Huntington's and epilepsy. Insights that arise from this research will be relevant to the study of these and other diseases.A detailed model for key processes involved in cerebral ischemic stroke will be developed. The model will be constrained by recent experimental studies and will be used to compare, contrast, and suggest mechanisms underlying observed behavior. Mathematical and computational methods will be used to: (i) identify key processes involved with ischemic stroke-like conditions; (ii) systematically understand mechanisms underlying the model's behavior; (iii) reduce the model's complexity. The model will also be used to better understand mechanisms underlying the neuroprotective role of stimulation of astrocyte ATP production.