Bouhrara Mustapha, Alisch Joseph S R, Khattar Nikkita, Kim Richard W, Rejimon Abinand C, Cortina Luis E, Qian Wenshu, Ferrucci Luigi, Resnick Susan M, Spencer Richard G
National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
BMJ Neurol Open. 2020 Jul 1;2(1):e000053. doi: 10.1136/bmjno-2020-000053. eCollection 2020.
Myelin loss and cerebral blood flow (CBF) decline are central features of several neurodegenerative diseases. Myelin maintenance through oligodendrocyte metabolism is an energy-demanding process, so that myelin homeostasis is particularly sensitive to hypoxia, hypoperfusion or ischaemia. However, in spite of its central importance, little is known about the association between blood supply and myelin integrity.
To assess associations between cortical and subcortical CBF, and subcortical myelin content, in critical brain white matter regions.
MRI was performed on a cohort of 67 cognitively unimpaired adults. Using advanced MRI methodology, we measured whole-brain longitudinal and transverse relaxation rates ( ), sensitive but non-specific markers of myelin content, and myelin water fraction (MWF), a direct surrogate of myelin content, as well as regional CBF, from each of these participants.
All quantitative relaxometry metrics were positively associated with CBF in all brain regions evaluated. These associations between MWF or and CBF, and, to a lesser extent, between and CBF, were statistically significant in most brain regions examined, indicating that lower regional cortical or subcortical CBF corresponds to a decrease in local subcortical myelin content. Finally, all relaxometry metrics exhibited a quadratic, inverted U-shaped, association with age; this is attributed to the development of myelination from young to middle age, followed by progressive loss of myelin in later years.
In this first study examining the association between local blood supply and myelin integrity, we found that myelin content declines with CBF across a wide age range of cognitively normal subjects.
髓鞘丢失和脑血流量(CBF)下降是几种神经退行性疾病的核心特征。通过少突胶质细胞代谢维持髓鞘是一个能量需求较高的过程,因此髓鞘稳态对缺氧、灌注不足或缺血尤为敏感。然而,尽管其至关重要,但关于血液供应与髓鞘完整性之间的关联却知之甚少。
评估关键脑白质区域皮质和皮质下CBF与皮质下髓鞘含量之间的关联。
对67名认知未受损的成年人进行了MRI检查。使用先进的MRI方法,我们测量了这些参与者全脑的纵向和横向弛豫率( ,髓鞘含量的敏感但非特异性标志物)、髓鞘水分数(MWF,髓鞘含量的直接替代指标)以及区域CBF。
在所有评估的脑区中,所有定量弛豫测量指标均与CBF呈正相关。MWF或 与CBF之间的这些关联,以及在较小程度上 与CBF之间的关联,在大多数检查的脑区中具有统计学意义,表明较低的区域皮质或皮质下CBF对应于局部皮质下髓鞘含量的减少。最后,所有弛豫测量指标与年龄呈二次方、倒U形关联;这归因于从年轻时到中年髓鞘形成的发展,随后在晚年髓鞘逐渐丢失。
在这项首次研究局部血液供应与髓鞘完整性之间关联的研究中,我们发现,在认知正常的广泛年龄范围内,髓鞘含量随CBF下降。