Satchell Margaret A, Lai Yichen, Kochanek Patrick M, Wisniewski Stephen R, Fink Ericka L, Siedberg Neal A, Berger Rachel P, DeKosky Steven T, Adelson P David, Clark Robert S B
Department of Critical Care Medicine, The Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
J Cereb Blood Flow Metab. 2005 Jul;25(7):919-27. doi: 10.1038/sj.jcbfm.9600088.
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.
先前的研究表明，受虐待儿童的创伤性脑损伤（TBI）患者会出现迟发性神经元死亡。目前尚不清楚这种迟发性神经元死亡的模式是凋亡还是坏死，而这一区别具有治疗意义。细胞色素c是电子传递链的一个组成部分，在细胞应激条件下可从线粒体中释放出来，随后它可启动凋亡并作为凋亡的生物标志物。为了解决这个问题，通过酶联免疫吸附测定（ELISA）法测定了67例患有TBI的婴幼儿（包括15例被诊断为受虐待的患者）的167份脑室脑脊液（CSF）样本中的细胞色素c浓度。对照组包括19例无创伤或脑膜炎的婴幼儿的腰椎脑脊液。采用针对多个受试者内部观察值进行调整的多变量模型来确定与脑脊液细胞色素c相关的临床变量。还在一部分TBI患者中检测了其他与凋亡相关的蛋白质。脑脊液细胞色素c升高与受虐性TBI（P=0.0001）和女性性别（P=0.04）独立相关，但与年龄、格拉斯哥昏迷量表评分或生存情况无关。其他与凋亡相关的蛋白质，包括Fas和半胱天冬酶-1，在TBI后脑脊液中升高，但不能独立区分意外性和受虐性TBI。这些数据表明，在被诊断为受虐待的TBI患者亚组中，通过脑脊液中细胞色素c的存在检测到的凋亡尤为突出。TBI后的凋亡程度似乎也与性别有关。针对TBI后凋亡，特别是在受虐待儿童和女孩中制定靶向策略似乎是合理的。
