The Role of Complement in Neurodevelopmental Impairment following Neonatal Hypoxic-Ischemic Encephalopathy
The Role of Complement in Neurodevelopmental Impairment following Neonatal Hypoxic-Ischemic Encephalopathy
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DOI：
10.1055/s-0029-1220793
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发表时间：
2009-10-01
影响因子：
2
通讯作者：
Lassiter, Herbert A.
中科院分区：
文献类型：
--
作者：
Aly, Hany;Khashaba, Mohamed T.;Lassiter, Herbert A.
越来越多的证据表明，补体激活在发生缺氧缺血性脑病（HIE）的婴儿急性缺氧缺血性脑损伤的发病机制中起作用。然而，补体激活与随后的神经损伤之间的关系尚不清楚。我们测试了一个假设，即在人类新生儿中，中枢神经系统缺氧缺血后补体激活与随后的神经发育异常的获得呈正相关。这项前瞻性研究包括18名出生时复苏后诊断为HIE的足月婴儿和7名对照婴儿。作为排除败血症和脑膜炎的常规检查的一部分，所有婴儿在出生后24小时内采集脑脊液（CSF）样本。用酶联免疫吸附法测定所有脑脊液样品的末端补体复合物（TCC）、补体组分9 （C9）和白蛋白的浓度。在6个月和12个月时进行神经学检查和丹佛发育筛查试验11。在18例HIE患者中，9例死亡，6例存活，但伴有明显的神经损伤，3例神经预后正常。15例死亡或存活结局异常的HIE患儿脑脊液中TCC平均浓度较对照组升高（P = 0.026）， C9平均浓度似有降低，但差异无统计学意义（P = 0.056）。与TCC浓度相似，异常结局婴儿脑脊液白蛋白浓度显著升高（p = 0.005）。本研究表明，出生时复苏后补体激活（表现为CNS TCC升高）与随后神经系统后遗症的发展和死亡呈正相关。需要进一步的研究纳入更大的样本量来证实这种联系。在补体抑制剂在新生儿窒息患者中进行临床试验之前，这一步至关重要。
Evidence has accumulated implicating complement activation in the pathogenesis of acute post-hypoxic-ischemic cerebral injury in infants who develop hypoxic-ischemic encephalopathy (HIE). However, the relationship between complement activation and subsequent neurological impairment is not known. We tested the hypothesis that in human neonates, post-hypoxic-ischemic complement activation within the central nervous system is positively associated with the acquisition of subsequent neurodevelopmental abnormalities. This prospective study included 18 full-term infants diagnosed with HIE following resuscitation at birth and seven control infants. Cerebrospinal fluid (CSF) samples were obtained from all infants in the first 24 hours of life as part of routine investigations to exclude sepsis and meningitis. Concentrations of terminal complement complexes (TCC), complement component 9 (C9), and albumin were quantified by enzyme-linked immunosorbent assay in all CSF samples. Neurological examination and Denver Developmental Screening Test 11 were performed at 6 and 12 months of life. Of the 18 HIE subjects, nine died, six survived with significant neurological impairment, and three had normal neurological outcomes. In the CSF of the 15 HIE infants who died or survived With abnormal outcomes, the mean concentration of TCC was increased compared with controls (P = 0.026) and the mean C9 concentration appeared to be decreased but the difference was not statistically significant (p = 0.056). Similar to the TCC concentration, the concentration of albumin in the CSF was significantly increased in infants with abnormal outcomes (p = 0.005). This study indicates that complement activation following resuscitation at birth, as manifested by increased TCC in the CNS, is positively correlated with the combination of the development Of Subsequent neurological sequelae and death. Further study incorporating larger sample sizes will be required to confirm this association. This step is essential before clinical trials of complement inhibitors can be justified in human neonates who suffer birth asphyxia.