Prenatal cerebral ischemia disrupts MRI-defined cortical microstructure through disturbances in neuronal arborization.
Prenatal cerebral ischemia disrupts MRI-defined cortical microstructure through disturbances in neuronal arborization.
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DOI：
10.1126/scitranslmed.3004669
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发表时间：
2013-01-16
影响因子：
17.1
通讯作者：
Back SA
中科院分区：
文献类型：
--
作者：
Dean JM;McClendon E;Hansen K;Azimi-Zonooz A;Chen K;Riddle A;Gong X;Sharifnia E;Hagen M;Ahmad T;Leigland LA;Hohimer AR;Kroenke CD;Back SA
早产存活的儿童在大脑皮层生长方面表现出持续的、原因不明的紊乱，并伴有认知和学习障碍。这些缺陷的潜在机制仍然不清楚。我们利用体外扩散磁共振成像在一个早产大动物模型中证明，脑缺血会损害皮层生长以及皮层分数各向异性（FA）的正常成熟性下降。对锥体神经元的分析显示，皮层缺陷与树突分支的扩展受损以及突触密度降低有关。总之，这些发现表明皮层FA异常与神经元形态发育紊乱之间存在联系。为了通过实验研究这种可能性，我们测量了树突分支的方向分布，并观察到它与理论上预测的在缺血后皮层FA升高的情况下各向异性增加的模式相符。我们得出结论，皮层生长障碍与皮层神经元的树突分支和突触形成的弥漫性紊乱有关，这可能是早产存活者认知和学习障碍的基础。此外，皮层FA的测量可能有助于无创性检测影响皮层发育的神经系统疾病。
Children who survive preterm birth exhibit persistent unexplained disturbances in cerebral cortical growth with associated cognitive and learning disabilities. The mechanisms underlying these deficits remain elusive. We used ex vivo diffusion magnetic resonance imaging to demonstrate in a preterm large-animal model that cerebral ischemia impairs cortical growth and the normal maturational decline in cortical fractional anisotropy (FA). Analysis of pyramidal neurons revealed that cortical deficits were associated with impaired expansion of the dendritic arbor and reduced synaptic density. Together, these findings suggest a link between abnormal cortical FA and disturbances of neuronal morphological development. To experimentally investigate this possibility, we measured the orientation distribution of dendritic branches and observed that it corresponds with the theoretically predicted pattern of increased anisotropy within cases that exhibited elevated cortical FA after ischemia. We conclude that cortical growth impairments are associated with diffuse disturbances in the dendritic arbor and synapse formation of cortical neurons, which may underlie the cognitive and learning disabilities in survivors of preterm birth. Further, measurement of cortical FA may be useful for noninvasively detecting neurological disorders affecting cortical development.
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