目的:动物研究表明,暴露于严重的环境缺氧几天可能对神经退行性疾病有有益的长期影响。因为,人类长期严重缺氧对大脑结构和功能的急性风险是不确定的,我们在健康人中进行了一项试点研究。
方法:我们在一项为期35天的研究中纳入了两名专业登山者(参与者A和B),该研究包括适应期和连续14天的氧气浓度在8%至8.8%之间。他们在七个时间点进行了脑磁共振成像,并在27个时间点进行了覆盖认知领域的认知测试。我们之前分析了血液神经元特异性烯醇化酶和神经丝轻链水平,during,缺氧后。
结果:在缺氧时,白质体积增加(最大值:A,4.3%±0.9%;B,4.5%±1.9%),而灰质体积(A,-1.5%±0.8%;B,-2.5%±0.9%)和脑脊液体积(A,-2.7%±2.4%;B,-5.9%±8.2%)下降。此外,数字(A,11-17;B,26-126)和卷(A,140%;B,285%)的白质高信号在缺氧时增加,但在3.5个月的恢复期后恢复到基线。白质弥散加权成像提示细胞毒性水肿形成。我们没有观察到认知表现或生化脑损伤标志物的变化。
结论:在高度选择的健康个体中,超过2周的严重持续常压低氧可引起脑形态的可逆变化,而认知功能或脑损伤标志物无临床相关变化。这一发现可能为评估缺氧在神经退行性疾病中的治疗潜力的未来转化研究铺平道路。
OBJECTIVE: Animal studies suggest that exposure to severe ambient hypoxia for several days may have beneficial long-term effects on neurodegenerative diseases. Because, the acute risks of exposing human beings to prolonged severe hypoxia on brain structure and function are uncertain, we conducted a pilot study in healthy persons.
METHODS: We included two professional mountaineers (participants A and B) in a 35-day study comprising an acclimatization period and 14 consecutive days with oxygen concentrations between 8% and 8.8%. They underwent cerebral magnetic resonance imaging at seven time points and a cognitive test battery covering a spectrum of cognitive domains at 27 time points. We analysed blood neuron specific enolase and neurofilament light chain levels before, during, and after hypoxia.
RESULTS: In hypoxia, white matter volumes increased (maximum: A, 4.3% ± 0.9%; B, 4.5% ± 1.9%) whilst gray matter volumes (A, -1.5% ± 0.8%; B, -2.5% ± 0.9%) and cerebrospinal fluid volumes (A, -2.7% ± 2.4%; B, -5.9% ± 8.2%) decreased. Furthermore, the number (A, 11-17; B, 26-126) and volumes (A, 140%; B, 285%) of white matter hyperintensities increased in hypoxia but had returned to baseline after a 3.5-month recovery phase. Diffusion weighted imaging of the white matter indicated cytotoxic edema formation. We did not observe changes in cognitive performance or biochemical brain injury markers.
CONCLUSIONS: In highly selected healthy individuals, severe sustained normobaric hypoxia over 2 weeks elicited reversible changes in brain morphology without clinically relevant changes in cognitive function or brain injury markers. The finding may pave the way for future translational studies assessing the therapeutic potential of hypoxia in neurodegenerative diseases.