Extracellular Mitochondria in Cerebrospinal Fluid and Neurological Recovery After Subarachnoid Hemorrhage

Abstract

Background and Purpose 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). Methods 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. Results 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. Conclusions This proof-of-concept study suggests that extracellular mitochondria may provide a “biomarker-like” glimpse into brain integrity and recovery after injury.

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