Extracellular Mitochondria in Cerebrospinal Fluid and Neurological Recovery After Subarachnoid Hemorrhage.
Extracellular Mitochondria in Cerebrospinal Fluid and Neurological Recovery After Subarachnoid Hemorrhage.
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DOI：
10.1161/strokeaha.117.017758
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发表时间：
2017-08
期刊：
影响因子：
8.3
通讯作者：
Hayakawa K
中科院分区：
文献类型：
--
作者：
Chou SH;Lan J;Esposito E;Ning M;Balaj L;Ji X;Lo EH;Hayakawa K
最近的研究表明，细胞外线粒体可能参与中风的病理生理。在这项研究中，我们评估了内源性细胞外线粒体在大鼠和人类蛛网膜下腔出血（SAH）后脑脊液（CSF）中的功能相关性。使用SAH的标准大鼠模型，其中使用管腔内缝合来缝合脑动脉，从而导致血液外渗到蛛网膜下腔中。在SAH后24和72小时，测量神经学结果，并使用标准JC1测定来定量CSF中的线粒体膜电位。为了进一步支持大鼠模型实验，从41名SAH患者和27名对照受试者获得CSF样品。使用JC 1测定法测量线粒体膜电位，并在3个月时评估与临床结果的相关性。在SAH的标准大鼠模型中，在损伤后24和72小时在CSF中检测到细胞外线粒体。JC1分析表明，与假手术对照组相比，SAH后CSF中的线粒体膜电位降低。在人CSF样品中，还检测到细胞外线粒体，并且在SAH后JC1水平也降低。此外，脑脊液中较高的线粒体膜电位与SAH发作后3个月的良好临床恢复相关。这项概念验证研究表明，细胞外线粒体可能提供了一个“生物标志物样”的一瞥大脑完整性和损伤后的恢复。
Recent studies suggest that extracellular mitochondria may be involved in the pathophysiology of stroke. In this study, we assessed the functional relevance of endogenous extracellular mitochondria in cerebrospinal fluid (CSF) in rats and humans after subarachnoid hemorrhage (SAH). A standard rat model of SAH was used, where an intraluminal suture was used to perforate a cerebral artery, thus leading to blood extravasation into subarachnoid space. At 24 and 72 hrs post-SAH, neurological outcomes were measured, and the standard JC1 assay was used to quantify mitochondrial membrane potentials in the CSF. To further support the rat model experiments, CSF samples were obtained from 41 SAH patients and 27 control subjects. Mitochondrial membrane potentials were measured with the JC1 assay, and correlations with clinical outcomes were assessed at 3 months. In the standard rat model of SAH, extracellular mitochondria was detected in CSF at 24 and 72 hrs after injury. JC1 assays demonstrated that mitochondrial membrane potentials in CSF were decreased after SAH compared with sham-operated controls. In human CSF samples, extracellular mitochondria were also detected, and JC1 levels were also reduced after SAH. Furthermore, higher mitochondrial membrane potentials in the CSF was correlated with good clinical recovery at 3 months after SAH onset. This proof-of-concept study suggests that extracellular mitochondria may provide a “biomarker-like” glimpse into brain integrity and recovery after injury.