Cytochrome c, a biomarker of apoptosis, is increased in cerebrospinal fluid from infants with inflicted brain injury from child abuse
Cytochrome c, a biomarker of apoptosis, is increased in cerebrospinal fluid from infants with inflicted brain injury from child abuse
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DOI：
10.1038/sj.jcbfm.9600088
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发表时间：
2005-07-01
影响因子：
6.3
通讯作者：
Clark, RSB
中科院分区：
文献类型：
--
作者：
Satchell, MA;Lai, YC;Clark, RSB
先前的研究表明，因虐待儿童而造成脑外伤（TBI）的患者会出现迟发性神经元死亡。目前尚不清楚这种延迟性神经元死亡的模式是否代表细胞凋亡或坏死，这是一种具有治疗影响的区别。细胞色素 c 是一种电子传递链成分，在细胞应激条件下可以从线粒体释放，从而启动细胞凋亡并充当细胞凋亡的生物标志物。为了解决这个问题，我们通过 ELISA 测定了 67 名患有 TBI 的婴儿和儿童（包括 15 名被诊断为虐待儿童的患者）的 167 份脑室脑脊液 (CSF) 样本中的细胞色素 c 浓度。对照包括 19 名没有外伤或脑膜炎的婴儿和儿童的腰椎脑脊液。使用针对多个受试者内观察进行调整的多变量模型来识别与 CSF 细胞色素 c 相关的临床变量。还在部分 TBI 患者中检查了其他凋亡相关蛋白。脑脊液细胞色素 c 增加与 TBI (P=0.0001) 和女性 (P=0.04) 独立相关，但与年龄、格拉斯哥昏迷量表评分或生存率无关。 TBI 后脑脊液中其他凋亡相关蛋白（包括 Fas 和 caspase-1）增加，但不能独立区分意外 TBI 和造成 TBI。这些数据表明，通过脑脊液中细胞色素 c 的存在检测到的细胞凋亡在被诊断为虐待儿童的 TBI 患者亚群中尤为突出。 TBI 后的细胞凋亡程度似乎也具有性别依赖性。制定针对 TBI 后细胞凋亡的策略，特别是针对虐待儿童的受害者和女孩，似乎是合理的。
Previous studies suggest that delayed neuronal death occurs in patients with inflicted traumatic brain injury (TBI) from child abuse. It is unknown whether the mode of this delayed neuronal death represents apoptosis or necrosis, a distinction that carries therapeutic ramifications. Cytochrome c, an electron transport chain component, can be released from mitochondria under conditions of cellular stress, whereupon it can initiate and serve as a biomarker of apoptosis. To resolve this issue, cytochrome c concentration was determined in 167 ventricular cerebrospinal fluid (CSF) samples from 67 infants and children with TBI (including 15 patients diagnosed with child abuse) by ELISA. Controls included lumbar CSF from 19 infants and children without trauma or meningitis. A multivariate model adjusted for multiple within-subject observations was used to identify clinical variables associated with CSF cytochrome c. Other apoptosis-related proteins were also examined in a subset of TBI patients. Increased CSF cytochrome c was independently associated with inflicted TBI (P=0.0001) and female gender (P=0.04), but not age, Glasgow coma scale score, or survival. Other apoptosis-related proteins including Fas and caspase-1 were increased in CSF after TBI, but did not independently discriminate between accidental and inflicted TBI. These data suggest that apoptosis, as detected by the presence of cytochrome c in CSF, is uniquely prominent among the subset of TBI patients diagnosed with child abuse. The degree of apoptosis after TBI also appears to be gender-dependent. Development of strategies targeting apoptosis after TBI, particularly in victims of child abuse and in girls, appears justified.