Neuron-specific enolase and S100B in cerebrospinal fluid after severe traumatic brain injury in infants and children
Neuron-specific enolase and S100B in cerebrospinal fluid after severe traumatic brain injury in infants and children
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DOI：
10.1542/peds.109.2.e31
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发表时间：
2002-02-01
期刊：
影响因子：
8
通讯作者：
Kochanek, PM
中科院分区：
文献类型：
--
作者：
Berger, RP;Pierce, MC;Kochanek, PM
背景资料。创伤性脑损伤是导致儿童死亡和残疾的主要原因。通过对重型非创伤性和创伤性脑损伤(nTBI和iTBI)患儿脑室脑脊液(CSF)的分析，人们对脑外伤后继发性损伤的机制有了相当深入的了解。神经元特异烯醇化酶(NSE)是一种糖酵解酶，主要定位于神经元细胞质。S100B是一种钙结合蛋白，定位于星形胶质细胞。在成人中，脑脊液和血清中NSE和S100B的浓度可作为脑外伤后神经元损伤的标志物。NSE和S100B在婴儿或儿童脑外伤后脑脊液中的研究尚未见报道。用快速酶联免疫吸附试验检测脑脊液中NSE和S100B的浓度，比较nTBI和iTBI后神经元和星形胶质细胞死亡的时程和程度。严重的nTBI和iTBI是由严格的临床标准定义的。脑室连续脑脊液标本35例，分别来自1.5~9岁重型颅脑损伤患儿(n=5)和0.2~1.5岁重型颅脑损伤患儿(n=5)。以5名被评估为脑膜炎的0.1岁至2.3岁儿童的腰椎脑脊液样本作为对照组。脑脊液NSE和S100B浓度用酶联免疫吸附试验(加拿大安大略省SynX Pharma Inc.)定量。ITBI患者(中位数[范围]：0.2岁[0.2-1.8])、nTBI患者(2.0岁[1.5-9])和对照组(0.2岁[0.2-1.8])之间的年龄没有差异。颅脑损伤组患者格拉斯哥昏迷评分(9[4-14])高于非颅脑损伤组(3[3-7])。在35例颅脑损伤患者中，有34例NSE高于对照组。平均NSE显著升高(平均+/-扫描电子显微镜，117.1+/-12.0 ng/mLvs3.5+/-1.4 ng/mLvs)。NTBI后NSE出现一过性峰值，中位数为伤后11小时(5~20小时)。颅脑损伤后，随着NSE的增加，持续的和延迟的峰值出现在损伤后的中位数63小时(范围：7-94)。NTBI和iTBI中NSE峰值的大小相似。在35个样本中，有35个样本S100B的表达水平高于对照组。颅脑损伤组S100B均值明显高于对照组(1.67+/-0.2 ng/mLvs0.02+/-0.0 ng/mLvs.S100B在nTBI和iTBI后27小时(5~63小时)出现单峰。S100B的平均浓度、峰值浓度和达峰时间与损伤机制无关。重型nTBI和iTBI后脑脊液中神经元和星形胶质细胞死亡的标志物显著增加。ITBI产生一个独特的NSE时程，以早峰和晚峰为特征，推测代表两波神经元死亡，其中第二波可能代表细胞凋亡。迟发性神经元死亡可能是脑外伤的一个重要治疗靶点。NSE和S100B也可作为识别隐匿性脑损伤的标志物，有助于区分非脑损伤和脑损伤，并有助于确定脑损伤的损伤时间。
Background. Traumatic brain injury (TBI) is a leading cause of death and disability in children. Considerable insight into the mechanisms involved in secondary injury after TBI has resulted from analysis of ventricular cerebrospinal fluid (CSF) obtained in children with severe noninflicted and inflicted TBI (nTBI and iTBI, respectively). Neuron-specific enolase (NSE) is a glycolytic enzyme that is localized primarily to the neuronal cytoplasm. S100B is a calcium-binding protein localized to astroglial cells. In adults, CSF and serum concentrations of NSE and S100B have served as markers of neuronal damage after TBI. Neither NSE nor S100B has previously been studied in CSF after TBI in infants or children.Objective. To compare the time course and magnitude of neuronal and astroglial death after nTBI and iTBI by measuring CSF concentrations of NSE and S100B using a rapid enzyme-linked immunosorbent assay.Methods. Severe nTBI and iTBI were defined by strict clinical criteria. Serial ventricular CSF samples (n = 35) were obtained from children 1.5 to 9 years with severe nTBI (n = 5) and children 0.2 to 1.5 years (n = 5) with severe iTBI. Lumbar CSF samples from 5 children 0.1 to 2.3 years evaluated for meningitis were used as a comparison group. CSF NSE and S100B concentrations were quantified by an enzyme-linked immunosorbent assay (SynX Pharma Inc, Ontario, Canada).Results. There was no difference in age between patients with iTBI (median [range]: 0.2 years [0.2-1.8]), nTBI (2.0 years [1.5-9]), and the comparison group (0.2 years [0.2-1.8]). The initial Glasgow Coma Scale score was higher in the iTBI group (9 [4-14]) versus the nTBI group (3 [3-7]). NSE was increased in TBI versus the comparison group in 34 of 35 samples. Mean NSE was markedly increased (mean +/- SEM, 117.1 +/- 12.0 ng/mL vs 3.5 +/- 1.4 ng/mL). After nTBI, a transient peak in NSE was seen at a median of 11 hours after injury (range: 5-20 hours). After iTBI, an increase in admission NSE was followed by a sustained and delayed peak at a median of 63 hours after injury (range: 7-94). The magnitude of peak NSE was similar in nTBI and iTBI. S100B was increased versus the comparison group in 35 of 35 samples. Mean S100B was markedly increased in TBI versus the comparison group (1.67 +/- 0.2 ng/mL vs 0.02 +/- 0.0 ng/mL). S100B showed a single peak at 27 hours (range: 5- 63 hours) after both nTBI and iTBI. The mean S100B concentration, peak S100B concentration, and the time to peak were not associated with mechanism of injury.Conclusions. Markers of neuronal and astroglial death are markedly increased in CSF after severe nTBI and iTBI. ITBI produces a unique time course of NSE, characterized by both an early and late peak, presumably representing 2 waves of neuronal death, the second of which may represent apoptosis. Delayed neuronal death may represent an important therapeutic target in iTBI. NSE and S100B may also be useful as markers to identify occult iTBI, help differentiate nTBI and iTBI, and assist in determining the time of injury in cases of iTBI.