Pathological Dynamics in a Neuron/Astrocyte Network Model

缺血性脑卒中是美国第三大死亡原因，仅次于癌症和心脏病。尽管有迫切的需求，但中风期间脑损伤的潜在机制在很大程度上仍然未知，目前治疗中风的策略在很大程度上是不成功的。该项目将建立一个详细的数学模型，用于确定在类缺血条件的产生中起决定性作用的机制和过程。钙信号和能量产生在许多细胞过程中起着关键作用，并与多种神经系统疾病有关，包括帕金森病、阿尔茨海默病、亨廷顿舞蹈症和癫痫。从这项研究中产生的见解将与这些疾病和其他疾病的研究有关。一个详细的模型涉及脑缺血中风的关键过程将被开发。该模型将受到最近实验研究的约束，并将用于比较、对比和提出观察到的行为背后的机制。数学和计算方法将用于：(i)确定与缺血性中风样疾病相关的关键过程；（ii）系统地理解模型行为背后的机制；（iii）降低模型的复杂度。该模型还将用于更好地理解刺激星形胶质细胞ATP产生的神经保护作用的机制。

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.