Metabolic activity in and metabolic support of malperfused brain tissue.

灌注不良脑组织的代谢活动和代谢支持。

• 批准号: 2391799
• 金额: --
• 依托单位: University of Warwick
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2391799
• 关键词: Metabolic; activity; metabolic; support; malperfused

The human brain consumes 20% of total oxygen (O2) while representing only 2% of the body mass. The main source of energy in human tissues including the brain is adenosine triphosphate (ATP). ATP enables all cellular process in the brain, such as protein synthesis, maintaining resting membrane potential or neurotransmitter cycling. Under physiological conditions, the rate of energy consumption is exactly balanced by the rate of ATP synthesis, which also correlates with the brain activity levels. Nevertheless, there is no ATP reservoir in the brain. That means that even short O2 deprivation have immediate and delayed detrimental effects on brain function. ATP metabolism produces adenosine, inosine and hypoxanthine, which are lost from the brain into circulation under conditions of cerebral malperfusion. Once lost, ATP production via the Purine Salvage Pathway (PSP), a biological pathway in which ATP levels are restored, is hindered. There is an age-related, steady increase in systolic blood pressure (BP) which is now considered part of the "normal" ageing process. The BP increase causes small artery remodelling, characterised by a decrease of vessel diameter, and increased wall thickness. Affected vessels, predominantly those situated in deep cortical grey matter and subcortical white matter areas and lacking substantial collaterals, become less capacious. As a result, cerebral blood flow (CBF) to downstream areas declines and a metabolic mismatch arises. This project aims to investigate the consequences of reduced CBF and disturbed PSP on the ageing brain. We will further investigate ways of PSP support as a potential measure to counter age- and CBF-related brain changes to support healthy brain function in the aging human population.

人类大脑消耗20%的总氧（O2），而仅占身体质量的2%。包括大脑在内的人体组织中的主要能量来源是三磷酸腺苷（ATP）。ATP使大脑中的所有细胞过程，如蛋白质合成，维持静息膜电位或神经递质循环。在生理条件下，能量消耗的速率与ATP合成的速率完全平衡，这也与大脑活动水平相关。然而，大脑中没有ATP储存库。这意味着，即使是短暂的缺氧也会对大脑功能产生即时和延迟的有害影响。ATP代谢产生腺苷、肌苷和次黄嘌呤，它们在脑灌注不良的情况下从脑损失到循环中。一旦丢失，通过嘌呤补救途径（PSP）（一种恢复ATP水平的生物途径）产生的ATP就会受到阻碍。收缩压（BP）有一个与年龄相关的稳定增加，现在被认为是“正常”衰老过程的一部分。血压升高导致小动脉重塑，其特征在于血管直径减小和壁厚增加。受影响的血管，主要是那些位于深层皮质灰质和皮质下白色物质区域，缺乏实质性侧支，变得不那么宽敞。结果，流向下游区域的脑血流量（CBF）下降，并出现代谢不匹配。该项目旨在研究CBF减少和PSP干扰对衰老大脑的影响。我们将进一步研究PSP支持的方法，作为对抗年龄和CBF相关脑变化的潜在措施，以支持老年人群的健康脑功能。