Lifelong exposure to high‐altitude hypoxia in humans is associated with improved redox homeostasis and structural?functional adaptations of the neurovascular unit
Lifelong exposure to high‐altitude hypoxia in humans is associated with improved redox homeostasis and structural?functional adaptations of the neurovascular unit
复制标题
人类终生暴露于高原缺氧与氧化还原稳态的改善和神经血管单元的结构功能适应有关
DOI：
10.1113/jp283362
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Bailey DM.
中科院分区：
文献类型：
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作者：
Stacey BS;Hoiland RL;Caldwell HG;Howe CA;Vermeulen T;Tymko MM;Vizcardo‐Galindo GA;Bermudez D;Figueroa‐Mujiica RJ;Gasho C;Tuaillon E;Hirtz C;Lehmann S;Marchi N;Tsukamoto H;Villafuerte FC;Ainslie PN;Bailey DM.
【摘要】高原缺氧可改变神经血管单元（NVU）的结构功能完整性。在此，我们比较了海拔（SL）的男性低地居民（n= 9）和在Pasco Cerro (CdP), p<s:1> (HA)适应4300米（慢性HA） 14天后，与性别、年龄和体重指数匹配的健康高原居民（n= 9）（终身HA）。静脉血检测反映NVU完整性的血清蛋白，以及自由基和一氧化氮（NO）。区域性脑血流量（CBF）与脑底物递送、动态脑自动调节（dCA）、脑血管对二氧化碳的反应性（CVRCO2）和神经血管耦合（NVC）一起检测。采用精神运动测试来检查认知功能。与低地人相比，高地人表现出更高的基础血浆和红细胞NO生物利用度，改善前路和后路dCA，提高前路cvrco2，并保留脑底物输送，NVC和认知。高原人在慢性HA后，S100B、神经丝轻链（NF - L）和T - tau持续降低，认知水平与低地人相当。这些发现强调了高地人对NVU调节的新的综合适应，这可能代表了一种神经保护表型，支持了对HA缺氧终身应激的成功适应。高海拔（HA）缺氧有可能改变人类神经血管单元（NVU）的结构-功能完整性。我们首次研究了慢性和终身缺氧对低地人和土著安第斯高地人反映NVU结构和功能的多模态生物标志物的影响程度。尽管低地人在慢性缺氧期间表现出全身氧化-亚硝化应激减少，并维持大脑生物能量和脑血管功能，但有证据表明轴突损伤和认知障碍增加。与海平面上的低地人相比，高原人的血管NO生物利用度提高，动态调节能力和脑血管反应性增强，脑底物传递和神经血管耦合能力相当，认知能力保持不变。与慢性HA后的低地人不同，高地人的S100B、神经丝轻链和总tau浓度较低。这些发现强调了高地人对NVU调节的新的综合适应，这可能代表了一种神经保护表型，支持了对HA缺氧终身应激的成功适应。
AbstractHigh‐altitude (HA) hypoxia may alter the structural–functional integrity of the neurovascular unit (NVU). Herein, we compared male lowlanders (n= 9) at sea level (SL) and after 14 days acclimatization to 4300 m (chronic HA) in Cerro de Pasco (CdP), Péru (HA), against sex‐, age‐ and body mass index‐matched healthy highlanders (n= 9) native to CdP (lifelong HA). Venous blood was assayed for serum proteins reflecting NVU integrity, in addition to free radicals and nitric oxide (NO). Regional cerebral blood flow (CBF) was examined in conjunction with cerebral substrate delivery, dynamic cerebral autoregulation (dCA), cerebrovascular reactivity to carbon dioxide (CVRCO2) and neurovascular coupling (NVC). Psychomotor tests were employed to examine cognitive function. Compared to lowlanders at SL, highlanders exhibited elevated basal plasma and red blood cell NO bioavailability, improved anterior and posterior dCA, elevated anterior CVRCO2and preserved cerebral substrate delivery, NVC and cognition. In highlanders, S100B, neurofilament light‐chain (NF‐L) and T‐tau were consistently lower and cognition comparable to lowlanders following chronic‐HA. These findings highlight novel integrated adaptations towards regulation of the NVU in highlanders that may represent a neuroprotective phenotype underpinning successful adaptation to the lifelong stress of HA hypoxia.Key pointsHigh‐altitude (HA) hypoxia has the potential to alter the structural–functional integrity of the neurovascular unit (NVU) in humans.For the first time, we examined to what extent chronic and lifelong hypoxia impacts multimodal biomarkers reflecting NVU structure and function in lowlanders and native Andean highlanders.Despite lowlanders presenting with a reduction in systemic oxidative–nitrosative stress and maintained cerebral bioenergetics and cerebrovascular function during chronic hypoxia, there was evidence for increased axonal injury and cognitive impairment.Compared to lowlanders at sea level, highlanders exhibited elevated vascular NO bioavailability, improved dynamic regulatory capacity and cerebrovascular reactivity, comparable cerebral substrate delivery and neurovascular coupling, and maintained cognition. Unlike lowlanders following chronic HA, highlanders presented with lower concentrations of S100B, neurofilament light chain and total tau.These findings highlight novel integrated adaptations towards the regulation of the NVU in highlanders that may represent a neuroprotective phenotype underpinning successful adaptation to the lifelong stress of HA hypoxia.