Resolving the transition from negative to positive blood oxygen level-dependent responses in the developing brain
Resolving the transition from negative to positive blood oxygen level-dependent responses in the developing brain
复制标题
DOI：
10.1073/pnas.1212785110
复制
发表时间：
2013-03-12
影响因子：
11.1
通讯作者：
Hillman, Elizabeth M. C.
中科院分区：
文献类型：
--
作者：
Kozberg, Mariel G.;Chen, Brenda R.;Hillman, Elizabeth M. C.
成年人的大脑表现出局部增加皮质血流量响应外部刺激。然而，据报道，新生儿和幼儿的大脑中存在广泛不同的血流动力学反应。特别是存在争议的“真正的”新生儿的刺激反应是否包括减少或增加的本地脱氧血红蛋白，对应于一个积极的（成人样）或消极的血氧水平依赖（BOLD）的信号在功能磁共振成像（fMRI），分别。先前研究的一个主要困难是人类受试者和测量范式的可变性。在这里，我们提出了一个系统的研究，在新生大鼠，图表的皮质血流反应在出生后的发展过程中，使用暴露的皮质多光谱光学成像的演变。我们证明，出生后第12-13天的大鼠（相当于人类新生儿）表现出“倒置”的血流动力学反应（增加脱氧血红蛋白，负BOLD）与早期迹象的耗氧量，随后延迟，主动收缩软脑膜动脉。我们观察到，血流动力学反应然后通过最初充血（阳性BOLD）阶段的发展而成熟，最终掩盖氧消耗并平衡血管收缩。我们还观察到，新生儿的反应特别容易受到刺激诱发的全身血压升高，导致皮质充血，类似于成人的阳性BOLD反应。我们认为，这种混淆可能占新生儿皮质血流动力学的先前研究的变异性。我们的研究结果表明，婴儿和儿童发育的功能磁共振成像研究可能会受到新生儿大脑成熟的神经血管和自动调节系统的深刻影响。
The adult brain exhibits a local increase in cortical blood flow in response to external stimulus. However, broadly varying hemodynamic responses in the brains of newborn and young infants have been reported. Particular controversy exists over whether the "true" neonatal response to stimulation consists of a decrease or an increase in local deoxyhemoglobin, corresponding to a positive (adult-like) or negative blood oxygen level-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI), respectively. A major difficulty with previous studies has been the variability in human subjects and measurement paradigms. Here, we present a systematic study in neonatal rats that charts the evolution of the cortical blood flow response during postnatal development using exposed-cortex multispectral optical imaging. We demonstrate that postnatal-day-12-13 rats (equivalent to human newborns) exhibit an "inverted" hemodynamic response (increasing deoxyhemoglobin, negative BOLD) with early signs of oxygen consumption followed by delayed, active constriction of pial arteries. We observed that the hemodynamic response then matures via development of an initial hyperemic (positive BOLD) phase that eventually masks oxygen consumption and balances vasoconstriction toward adulthood. We also observed that neonatal responses are particularly susceptible to stimulus-evoked systemic blood pressure increases, leading to cortical hyperemia that resembles adult positive BOLD responses. We propose that this confound may account for much of the variability in prior studies of neonatal cortical hemodynamics. Our results suggest that functional magnetic resonance imaging studies of infant and child development may be profoundly influenced by the maturing neurovascular and autoregulatory systems of the neonatal brain.