Hypoxia reveals posterior thalamic, cerebellar, midbrain, and limbic deficits in congenital central hypoventilation syndrome
Hypoxia reveals posterior thalamic, cerebellar, midbrain, and limbic deficits in congenital central hypoventilation syndrome
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DOI：
10.1152/japplphysiol.00969.2004
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发表时间：
2005-03-01
影响因子：
3.3
通讯作者：
Harper, RM
中科院分区：
文献类型：
--
作者：
Macey, PM;Woo, MA;Harper, RM
先天性中枢性通气不足综合征（CCHS）患者表现出对缺氧和高碳酸血症的呼吸和心脏反应不足，尽管对高碳酸血症的唤醒反应明显完整且有足够的呼吸运动机制，从而提供了一个模型来评估呼吸背后的特定大脑机制的功能。我们使用功能磁共振成像来评估血氧水平依赖性信号，校正全局信号变化，并在 14 名 CCHS 和 14 名年龄和性别匹配的对照受试者中进行基线和 2 分钟低氧（15% O-2，85% N-2）挑战期间，通过聚类和感兴趣体积程序对其进行评估。缺氧引起各组之间小脑皮质和深部核团、后丘脑结构、边缘区（包括岛叶、杏仁核、腹侧前丘脑和右侧海马）、背侧和腹侧中脑、尾状核、屏状核和壳核的反应幅度和时间存在显着差异（P < 0.05）。对缺氧的反应不足包括 CCHS 患者无变化或晚期变化，而对照受试者信号下降，CCHS 患者信号下降而对照无变化，或 CCHS 缺乏早期短暂反应。缺氧导致信号下降，但下丘脑和背髓质区域没有组间差异，后者是 PHOX2B 的靶点，该综合征中发生了 PHOX2B 的突变。这些发现扩展了先前确定的后丘脑、中脑和小脑在动物胎儿和成人制剂中发现的缺氧正常调节中的作用，并表明边缘结构在应对缺氧挑战中发挥着重要作用，其中可能包括心血管和空气饥饿成分。 CCHS 中的失败结构包括与 PHOX2B 表达和化学感受器位点相关的区域以外的区域。
Congenital central hypoventilation syndrome (CCHS) patients show deficient respiratory and cardiac responses to hypoxia and hypercapnia, despite apparently intact arousal responses to hypercapnia and adequate respiratory motor mechanisms, thus providing a model to evaluate functioning of particular brain mechanisms underlying breathing. We used functional magnetic resonance imaging to assess blood oxygen level-dependent signals, corrected for global signal changes, and evaluated them with cluster and volume-of-interest procedures, during a baseline and 2-min hypoxic (15% O-2, 85% N-2) challenge in 14 CCHS and 14 age- and gender-matched control subjects. Hypoxia elicited significant ( P < 0.05) differences in magnitude and timing of responses between groups in cerebellar cortex and deep nuclei, posterior thalamic structures, limbic areas ( including the insula, amygdala, ventral anterior thalamus, and right hippocampus), dorsal and ventral midbrain, caudate, claustrum, and putamen. Deficient responses to hypoxia included no, or late, changes in CCHS patients with declining signals in control subjects, a falling signal in CCHS patients with no change in controls, or absent early transient responses in CCHS. Hypoxia resulted in signal declines but no group differences in hypothalamic and dorsal medullary areas, the latter being a target for PHOX2B, mutations of which occur in the syndrome. The findings extend previously identified posterior thalamic, midbrain, and cerebellar roles for normal mediation of hypoxia found in animal fetal and adult preparations and suggest significant participation of limbic structures in responding to hypoxic challenges, which likely include cardiovascular and air-hunger components. Failing structures in CCHS include areas additional to those associated with PHOX2B expression and chemoreceptor sites.