老化與腦微循環：生命期間氧氣輸送、傳遞時間分布和管壁剪應力的影響

Abstract

老化顯著改變了人類大腦微血管系統的結構，影響了氧氣代謝和運輸。目前的模型專注於健康成年人的大腦，並未考慮老化相關的變化，而這些變化對於研究神經退行性疾病至關重要。微血管通過時間異質性 (CTH)與平均通過時間 (MTT)的比值，稱為通過時間異質性比(RTH)，作為壁剪切應力(WSS)變異性的指標。數值模擬在任意網絡和10個統計生成的微血管立方體中進行。人類大腦微血管模型通過修剪血管並基於三個不同年齡組的老鼠的活體測量數據創建連續的老化梯度來適應老化。計算了不同年齡組的通過時間分佈，並比較了這些組別的氧氣提取分數(OEF)、大腦氧氣代謝率 (CMRO2)和氧氣的分壓 (PO2)。RTH與網絡的氧氣提取分數成反比，並受老化和疾病等生理變化的影響，因此成為血管健康的重要標誌。在老化的大腦中，CMRO2每年下降0.94%，PO2每年下降0.12%，而OEF每年增加0.24%。年齡是開發用於評估微血管健康和認知衰退風險因素的in-silico模型的重要因素。CMRO2隨年齡的變化改變了對缺氧的脆弱性，影響了灌注。隨著CMRO2恆定的情況下增加腦血流量(CBF)，缺氧部分呈非線性減少；而隨著CBF恆定的情況下增加CMRO2，PO2呈非線性減少。

Ageing significantly alters the structure of the human cerebral microvasculature, impacting oxygen metabolism and transport. Existing models focus on the brains of healthy adults and do not account for the changes associated with ageing, which are crucial for studying neurodegenerative diseases. The ratio of capillary transit time heterogeneity (CTH) to mean transit time (MTT), referred to as ratio of transit time heterogeneity (RTH), serves as an indicator of wall shear stress (WSS) variability. Numerical simulations were conducted in arbitrary networks and 10 statistically generated microvascular cubes. The human cerebral microvasculature model was adapted for ageing by pruning vessels and creating a continuous ageing gradient based on in vivo measurements from mice in three different age groups. The transit time distribution for different age groups was calculated, and the oxygen extraction fraction (OEF), cerebral metabolic rate of oxygen (CMRO2), and partial pressure of oxygen PO2 were compared across these groups.

RTH is inversely proportional to the network's oxygen extraction fraction and is influenced by physiological changes such as ageing and disease, making it a valuable marker of vascular health. In the ageing brain, CMRO2 decreases by 0.94% per year, PO2 decreases by 0.12% per year, and OEF increases by 0.24% per year. Age is a crucial factor in developing in-silico models to assess microvascular health and cognitive decline risk factors. Changes in CMRO2 with age alter vulnerability to hypoxia, affecting perfusion. Increasing cerebral blood flow (CBF) with constant CMRO2 decreases the hypoxic fraction nonlinearly, while increases in CMRO2 with constant CBF nonlinearly decrease PO2.