Sawaguchi Toshiko, Patricia Franco, Kadhim Hazim, Groswasser Jose, Sottiaux Martine, Nishida Hiroshi, Kahn Andre
Department of Legal Medicine,Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku, Tokyo 162-8666, Japan.
Early Hum Dev. 2003 Dec;75 Suppl:S87-97. doi: 10.1016/j.earlhumdev.2003.08.012.
Microtubule-associated protein 2(MAP2), a cytoskeletal protein of the neuron, is a marker of early ischemic neuronal damage. As a chronic hypoxic situation exists in the brains of victims of the sudden infant death syndrome (SIDS), the correlation between MAP2-positive neurons or dendritic spines in the brainstem and sleep apnea was investigated in SIDS, which is still the main cause of postneonatal infant death.
27,000 infants were studied prospectively to characterize their sleep-wake behavior and amongst these, 38 infants died under 6 months of age. They included 26 cases of SIDS. The frequency and duration of sleep apneae were analyzed. The brainstem material was collected and immunohistochemistry of MAP2 was carried out. The density of MAP2-positive neurons, dendrites and dendritic spines were measured quantitatively. Correlation analyses were carried out between the MAP2-associated pathological data and the physiological data of sleep apnea.
One negative correlation between the density of MAP2-positive dendrites in the pars compacta of pedunculo-pontine tegmentum nucleus (PPTNc) and the duration of obstructive apnea (p=0.017) and two SIDS-specific positive correlations between the density of MAP2-positive dendrites in the pars dissipata of pedunculo-pontine tegmentum nucleus (PPTNd) and the duration of central apnea (p=0.005) and between the dorsal raphe and the frequency of obstructive apnea were found in SIDS victims. The density of MAP2-positive dendritic spines in PPTNc was significantly higher in SIDS than in control (p=0.034).
The significant correlations with the MAP2-positive findings in the midbrain arousal pathway and the characteristics of sleep apnea in SIDS victims were in agreement with the association with apnea and arousal-deficiency in SIDS.
微管相关蛋白2（MAP2）是神经元的一种细胞骨架蛋白，是早期缺血性神经元损伤的标志物。由于婴儿猝死综合征（SIDS）受害者的大脑中存在慢性缺氧情况，因此在SIDS（仍是新生儿期后婴儿死亡的主要原因）中研究了脑干中MAP2阳性神经元或树突棘与睡眠呼吸暂停之间的相关性。
对27000名婴儿进行前瞻性研究以表征其睡眠-觉醒行为，其中38名婴儿在6个月龄前死亡。包括26例SIDS病例。分析了睡眠呼吸暂停的频率和持续时间。收集脑干材料并进行MAP2免疫组织化学。定量测量MAP2阳性神经元、树突和树突棘的密度。对与MAP2相关的病理数据和睡眠呼吸暂停的生理数据进行相关性分析。
在SIDS受害者中，脚桥被盖核致密部（PPTNc）中MAP2阳性树突的密度与阻塞性呼吸暂停的持续时间呈负相关（p = 0.017），脚桥被盖核弥散部（PPTNd）中MAP2阳性树突的密度与中枢性呼吸暂停的持续时间呈正相关（p = 0.005），以及中缝背核与阻塞性呼吸暂停的频率呈正相关。SIDS中PPTNc中MAP2阳性树突棘的密度显著高于对照组（p = 0.034）。
中脑觉醒通路中MAP2阳性结果与SIDS受害者睡眠呼吸暂停特征之间的显著相关性与SIDS中呼吸暂停和觉醒不足的关联一致。
