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

能量产生与大脑活动之间的密切关系 神经系统中的血液流动是由高代谢 大脑的需求。 事实上，据估计， 成人大脑消耗大约4 × 10 21个ATP分子 每分钟，或近20%的所有能量产生的身体。 几乎 所有用于维持细胞基本功能的能量 来源于葡萄糖的有氧氧化。 因为大脑提取物 从动脉血中获得约50%的氧气和约10%的葡萄糖。 任何 CBF的显著减少可能会产生深远的影响， 神经元功能和存活。 现在人们普遍认为，急性代谢反应的神经 损伤的特征是葡萄糖的立即增加 新陈代谢. 奇怪的是，这种葡萄糖代谢的显著增加 TBI后，伴随着大脑皮层的持续减少， 血流（，1996）。 此外，氧化能力的测量 在实验性TBI后，使用细胞色素氧化酶组织化学 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降低。 拟议 研究调和这些挑衅性的发现，并提供支持， 新陈代谢和血流之间的分离 深刻影响受损神经元的长期生存能力， 决定了头部受伤后的最终结果。 因此，我们假设实验性TBI诱导一种状态，其中： I）葡萄糖代谢在前几个月急剧增加 小时，以试图重新建立神经元稳态，以及ii） 受损神经元产生的能量（ATP）不足， 满足由于蜂窝网络受损而增加的能源需求 代谢机制和损伤引起的神经血管变化 系统 为了评估这一普遍假设，本项目的具体目标 为： 1. 以确定是什么导致了这种分离。 到期了吗 导致异常高的能量需求吗 是因为 血管反应性丧失（代谢自动调节丧失）？ 2. 到 确定TBI诱导的葡萄糖代谢解偶联， 脑血流导致延迟的细胞死亡。 3. 以确定 受损神经元发生延迟细胞凋亡的细胞机制 死亡 是由于能量衰竭（ATP耗竭）吗？ 是不是到期了 大量钙离子螯合导致的细胞凋亡 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?