Extracellular Mitochondrial Dysfunction in Cerebrospinal Fluid of Patients with Delayed Cerebral Ischemia after Aneurysm

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ORIGINAL WORK

Extracellular Mitochondrial Dysfunction in Cerebrospinal Fluid of Patients with Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage Dong Hyuk Youn1, Bong Jun Kim1, Youngmi Kim1 and Jin Pyeong Jeon1,2,3*  © 2020 Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society

Abstract  Background:  Mitochondrial dysfunction is related to brain ischemic injury and neural cell death. However, little is known about the association between mitochondrial dysfunction of cerebrospinal fluid (CSF) and delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). The objective of this study was to investigate whether extracellular CSF mitochondria might serve as a potential biomarker for DCI. Methods:  CSF samples were serially collected at 1, 3, and 5 days following SAH in 33 patients (DCI, n = 12; and nonDCI, n = 21) who underwent coil embolization. To monitor mitochondrial membrane potentials, JC-1 dye was used. The ratio (red/green) of JC-1 was considered as an indicator of intact mitochondrial membrane potential. Flow cytometry was done to analyze extracellular mitochondria particles and their possible cellular origins. Results:  DCI patients had lower JC-1 red/green ratios than non-DCI patients at 1 day (3.35 [3.20–3.75] vs. 3.70 [3.40– 3.95] in non-DCI) and 3 days (4.65 [4.45–5.00] vs. 5.10 [4.65–5.30] in non-DCI) after SAH. At 5 days after SAH, JC-1 red/ green ratio was significantly lower in DCI than that in non-DCI (3.05 [2.90–3.35] vs. 4.20 [4.10–4.50]; p