Vlasova Roza M, Wang Qian, Willette Auriel, Styner Martin A, Lubach Gabriele R, Kling Pamela J, Georgieff Michael K, Rao Raghavendra B, Coe Christopher L
Department of Psychiatry, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, United States.
Front Hum Neurosci. 2021 Feb 24;15:624107. doi: 10.3389/fnhum.2021.624107. eCollection 2021.
A high percent of oxidative energy metabolism is needed to support brain growth during infancy. Unhealthy diets and limited nutrition, as well as other environmental insults, can compromise these essential developmental processes. In particular, iron deficiency anemia (IDA) has been found to undermine both normal brain growth and neurobehavioral development. Even moderate ID may affect neural maturation because when iron is limited, it is prioritized first to red blood cells over the brain. A primate model was used to investigate the neural effects of a transient ID and if deficits would persist after iron treatment. The large size and postnatal growth of the monkey brain makes the findings relevant to the metabolic and iron needs of human infants, and initiating treatment upon diagnosis of anemia reflects clinical practice. Specifically, this analysis determined whether brain maturation would still be compromised at 1 year of age if an anemic infant was treated promptly once diagnosed. The hematology and iron status of 41 infant rhesus monkeys was screened at 2-month intervals. Fifteen became ID; 12 met clinical criteria for anemia and were administered iron dextran and B vitamins for 1-2 months. MRI scans were acquired at 1 year. The volumetric and diffusion tensor imaging (DTI) measures from the ID infants were compared with monkeys who remained continuously iron sufficient (IS). A prior history of ID was associated with smaller total brain volumes, driven primarily by significantly less total gray matter (GM) and smaller GM volumes in several cortical regions. At the macrostructual level, the effect on white matter volumes (WM) was not as overt. However, DTI analyses of WM microstructure indicated two later-maturating anterior tracts were negatively affected. The findings reaffirm the importance of iron for normal brain development. Given that brain differences were still evident even after iron treatment and following recovery of iron-dependent hematological indices, the results highlight the importance of early detection and preemptive supplementation to limit the neural consequences of ID.
婴儿期大脑生长需要高比例的氧化能量代谢来支持。不健康的饮食、有限的营养以及其他环境损害，都会损害这些重要的发育过程。特别是，缺铁性贫血（IDA）已被发现会破坏正常的大脑生长和神经行为发育。即使是中度缺铁也可能影响神经成熟，因为当铁有限时，它会优先供应红细胞而非大脑。使用灵长类动物模型来研究短暂缺铁的神经影响以及铁治疗后缺陷是否会持续存在。猴子大脑的大尺寸和出生后的生长情况使得研究结果与人类婴儿的代谢和铁需求相关，并且在诊断贫血后立即开始治疗反映了临床实践。具体而言，该分析确定了如果贫血婴儿一旦确诊就立即接受治疗，其大脑成熟在1岁时是否仍会受到损害。每隔2个月对41只恒河猴幼崽的血液学和铁状态进行筛查。15只出现缺铁；12只符合贫血临床标准，并接受了1 - 2个月的右旋糖酐铁和B族维生素治疗。在1岁时进行了MRI扫描。将缺铁婴儿的体积和扩散张量成像（DTI）测量结果与持续铁充足（IS）的猴子进行比较。缺铁的既往史与较小的全脑体积相关，主要是由于显著更少的总灰质（GM）以及几个皮质区域中较小的GM体积。在宏观结构水平上，对白质体积（WM）的影响不那么明显。然而，WM微观结构的DTI分析表明，两条成熟较晚的前束受到了负面影响。这些发现再次证实了铁对正常大脑发育的重要性。鉴于即使在铁治疗后以及铁依赖的血液学指标恢复后大脑差异仍然明显，结果强调了早期检测和预防性补充以限制缺铁对神经影响的重要性。
