DETECT GROWTH PATTERNS IN DEVELOP HUMAN BRAIN: CONTINUUM MECHANIC TENSOR MAP

能量生产与大脑的密切关系 神经系统中的血液流动是由高代谢所必需的 大脑的需求。事实上，据估计，平均 成人大脑消耗大约4x1021个三磷酸腺苷分子 每分钟，或者说几乎占身体产生的所有能量的20%。差不多了 所有用于维持基本细胞功能的能量都是 来源于葡萄糖的有氧氧化。因为大脑提取的 -50%的氧气和-10%的葡萄糖来自动脉血。任何 CBF的显著减少可能会在 神经元的功能和生存。 现在已经很好地接受了对神经的急性代谢反应 损伤的特征是血糖立即升高。 新陈代谢。矛盾的是，这显著增加了葡萄糖新陈代谢 颅脑损伤后伴随着脑组织持续性下降 血流量(，1996)。此外，氧化能力的测量 实验性颅脑损伤后细胞色素氧化酶组织化学研究 表明线粒体功能的某些限制，这可能 表现为氧化代谢的慢性下降。建议数 研究调和了这些挑衅性的发现，并为 新陈代谢和血流之间的脱钩假说 深刻影响受损神经元的长期生存能力 决定了头部损伤后的最终结果。 因此，我们假设实验性的TBI诱导了一种状态，在这种状态下： I)在前几个阶段，葡萄糖新陈代谢显著增加 几个小时，试图重建神经元稳态，以及ii) 受损的神经元产生的能量不足(ATP) 满足因蜂窝网络受损而增加的能源需求 代谢机制与损伤引起的神经血管改变 系统。 为了评估这一普遍假设，该项目的具体目标 包括： 1.确定是什么导致了这种脱钩。它到期了吗？ 伤病引起的异常高的能量需求？是不是因为 血管反应性丧失(代谢自动调节丧失)？2。 确定脑损伤是否导致糖代谢解偶联和 脑血流导致延迟性细胞死亡。3.确定 损伤神经元经历延迟细胞的细胞机制 死亡。是否由于能量衰竭(三磷酸腺苷耗尽)？是不是到期了？ 大量钙离子封存导致的细胞凋亡？是不是因为 高糖酵解率导致的乳酸酸中毒？

The tight relationship between energy production and cerebral blood flow in the nervous system is necessitated by the high metabolic demands of the brain. In fact, it has been estimated that the average adult human brain consumes approximately 4 x 10 21 molecules of ATP per minute, or nearly 20% of all energy produced in the body. Almost all of the energy used to maintain basal cellular functioning is derived from aerobic oxidation of glucose. Since the brain extracts -50% of oxygen and -10% of glucose from the arterial blood. any significant reductions in CBF can have profound consequences in neuronal functioning and survival. It is now well accepted that the acute metabolic response to neural injury is characterized by an immediate increase in glucose metabolism. Paradoxically, this marked increase in glucose metabolism following TBI is accompanied by a persistent decrease in cerebral blood flow (, 1996). In addition, measurements of oxidative capacity after experimental TBI using cytochrome oxidase histochemistry indicates certain limitations in mitochondrial functioning, which may manifest as chronic decreases in oxidative metabolism. The proposed studies reconcile these provocative findings and provide support for the hypothesis that the uncoupling between metabolism and blood flow profoundly affects the long-term viability of injured neurons and determines the eventual outcome after head injury. Thus, we hypothesize that experimental TBI induces a state in which: I) glucose metabolism increases dramatically for the first several hours in an attempt to re-establish neuronal homeostasis, and ii) insufficient amount of energy (ATP) is produced by damaged neurons to meet this increased energy demand due to a compromised cellular metabolic machinery and injury-induced changes to the neurovascular system. To assess this general hypothesis, the specific aims of this project are: 1. To determine what is responsible for this uncoupling. Is it due to unusually high energy demands induced by the injury? Is it due to the loss of vasoreactivity (loss of metabolic autoregulation)? 2. To determine whether TBI-induced uncoupling of glucose metabolism and cerebral blood flow results in delayed cell death. 3. To determine the cellular mechanism by which injured neurons undergo delayed cell death. Is t due to energy failure (depletion of ATP)? Is it is due to apoptosis resulting from a massive Ca sequestration? Is it due to lactic acidosis resulting from high rates of glycolysis?