Cerebrospinal fluid mitochondrial DNA: a novel DAMP in pediatric traumatic brain injury.
Cerebrospinal fluid mitochondrial DNA: a novel DAMP in pediatric traumatic brain injury.
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DOI：
10.1097/shk.0000000000000160
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发表时间：
2014-06
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影响因子：
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通讯作者：
Aneja RK
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作者：
Walko TD 3rd;Bola RA;Hong JD;Au AK;Bell MJ;Kochanek PM;Clark RS;Aneja RK
危险相关分子模式（DAMP）是从受损组织释放并激活先天免疫系统的细胞核或细胞质蛋白。线粒体DNA（mtDNA）是一种新型的DAMP，在细胞死亡和损伤后释放到细胞外环境中。我们假设创伤性脑损伤（TBI）儿童中枢神经系统内的细胞死亡将导致mtDNA释放到脑脊液（CSF）中，并有可能预测创伤后的结果。CSF采集自重度TBI儿童，需要通过外部脑室引流进行颅内压监测，格拉斯哥昏迷量表（GCS）评分≤ 8。对照CSF是在没有TBI或脑膜脑炎的儿童中获得的，这些儿童在诊断性腰椎穿刺中没有白细胞。TBI患者的中位年龄为6.3岁，62%为男性。常见的损伤机制包括机动车碰撞（35.8%），其次是福尔斯（21.5%）和TBI（19%）; 6名儿童（14.2%）在ICU过程中死亡。在儿童TBI和对照人群中，平均CSF mtDNA浓度分别为1.10E +05 ± 2.07E+05和1.63E+03 ± 1.80E+03拷贝/微升。此外，后来死亡或严重残疾的儿童患者的平均CSF mtDNA浓度显著高于幸存者（1.63E+ 05 ± 2.77E+05 vs. 5.05E+04 ± 6.21E+04拷贝/微升）（p<0.0001）。我们发现CSF mtDNA和HMGB 1（另一种典型DAMP）浓度之间存在显著相关性（ρ = 0.574，p<0.05），支持TBI后CSF中两种DAMP均增加的观点。我们的数据表明，CSF mtDNA是TBI中的新DAMP，并且似乎是与TBI后的神经学结果相关的有用生物标志物。进一步探讨线粒体DNA中调节先天免疫反应的成分将有助于理解TBI后局部和全身炎症反应的机制。
Danger associated molecular patterns (DAMPs) are nuclear or cytoplasmic proteins that are released from the injured tissues and activate the innate immune system. Mitochondrial DNA (mtDNA) is a novel DAMP that is released into the extracellular milieu subsequent to cell death and injury. We hypothesized that cell death within the central nervous system in children with traumatic brain injury (TBI) would lead to release of mtDNA into the cerebrospinal fluid (CSF) and has the potential to predict the outcome after trauma. CSF was collected from children with severe TBI that required intracranial pressure monitoring with Glasgow Coma Scale (GCS) scores ≤ 8 via an externalized ventricular drain. Control CSF was obtained in children without TBI or meningoencephalitis that demonstrated no leukocytes in the diagnostic lumbar puncture. The median age for patients with TBI was 6.3 y and 62% were male. The common mechanisms of injury included motor vehicle collision (35.8%) followed by falls (21.5%) and inflicted TBI (19%); 6 children (14.2%) died during their ICU course. The mean CSF mtDNA concentration was 1.10E +05 ± 2.07E+05 and 1.63E+03 ± 1.80E+03 copies/µL in the pediatric TBI and control population respectively. Furthermore, the mean CSF mtDNA concentration in pediatric patients who later died or had severe disability was significantly higher than that of the survivors (1.63E+ 05 ± 2.77E+05 vs. 5.05E+04 ± 6.21E+04 copies/µL) (p<0.0001). We found a significant correlation between CSF mtDNA and HMGB1, another prototypical DAMP, concentrations (ρ = 0.574, p<0.05), supporting the notion that both DAMPs are increased in the CSF following TBI. Our data suggest that CSF mtDNA is novel DAMP in TBI, and appears to be a useful biomarker that correlates with neurological outcome after TBI. Further inquiry into the components of mtDNA that modulate the innate immune response will be helpful in understanding the mechanism of local and systemic inflammation after TBI.