Detection of brain specific cardiolipins in plasma after experimental pediatric head injury
Detection of brain specific cardiolipins in plasma after experimental pediatric head injury
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DOI：
10.1016/j.expneurol.2019.04.007
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发表时间：
2019-06-01
影响因子：
5.3
通讯作者：
Bayir, Huelya
中科院分区：
文献类型：
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作者：
Anthonymuthu, Tamil S.;Kenny, Elizabeth M.;Bayir, Huelya
心磷脂（CL）是一种线粒体特异性磷脂，对维持和调节线粒体生物能量和代谢功能至关重要。CL分子种类显示出很大的组织变异性，大脑显示出独特的、高度多样化的CL群体。我们最近表明，血浆中独特的脑型CL的出现可以作为心脏骤停后患者线粒体/组织损伤的脑特异性标志物。线粒体功能障碍已越来越多地被认为是创伤性脑损伤（TBI）发病机制的关键机制。因此，我们假设，独特的，脑特异性CL物种从受伤的大脑释放到外周循环后TBI。为了验证这一假设，我们进行了高分辨率质谱为基础的磷脂组学分析出生后第17天（PND）大鼠大脑和血浆后，控制皮质的影响。我们发现，TBI后血浆CL呈时间依赖性增加，包括损伤后早期的上述脑特异性CL种类，而CL在损伤的脑中显著降低。成分和定量相关分析表明，可能释放CL进入体循环TBI后。体循环中脑型CL的鉴定可指示TBI后潜在的线粒体功能障碍/损失。它们可能具有作为靶向治疗的药效学反应生物标志物的潜力。
Cardiolipin (CL) is a mitochondria-specific phospholipid that is central to maintenance and regulation of mitochondrial bioenergetic and metabolic functions. CL molecular species display great tissue variation with brain exhibiting a distinct, highly diverse CL population. We recently showed that the appearance of unique brain-type CLs in plasma could serve as a brain-specific marker of mitochondrial/tissue injury in patients after cardiac arrest. Mitochondrial dysfunction has been increasingly implicated as a critical mechanism underlying the pathogenesis of traumatic brain injury (TBI). Therefore, we hypothesized that unique, brain-specific CL species from the injured brain are released to the peripheral circulation after TBI. To test this hypothesis, we performed a high-resolution mass spectrometry based phospholipidomics analysis of post-natal day (PND)17 rat brain and plasma after controlled cortical impact. We found a time-dependent increase in plasma CLs after TBI including the aforementioned brain-specific CL species early after injury, whereas CLs were significantly decreased in the injured brain. Compositional and quantitative correlational analysis suggested a possible release of CL into the systemic circulation following TBI. The identification of brain-type CLs in systemic circulation may indicate underlying mitochondrial dysfunction/loss after TBI. They may have potential as pharmacodynamics response biomarkers for targeted therapies.