TY - JOUR

T1 - Elevated miR-9 in Cerebrospinal Fluid Is Associated with Poor Functional Outcome After Subarachnoid Hemorrhage

AU - Bache, Søren

AU - Rasmussen, Rune

AU - Wolcott, Zoe

AU - Rossing, Maria

AU - Møgelvang, Rasmus

AU - Tolnai, Daniel

AU - Hassager, Christian

AU - Forman, Julie L.

AU - Køber, Lars

AU - Nielsen, Finn Cilius

AU - Kimberly, William T.

AU - Møller, Kirsten

PY - 2020

Y1 - 2020

N2 - This study evaluated microRNA (miRNA) changes in cerebrospinal fluid (CSF) and their association with the occurrence of delayed cerebral ischemia (DCI) and poor functional outcome after SAH. Forty-three selected miRNAs were measured in daily CSF samples from a discovery cohort of SAH patients admitted to Rigshospitalet, Copenhagen, Denmark, and compared with neurologically healthy patients. Findings were validated in CSF from a replication cohort of SAH patients admitted to Massachusetts General Hospital, Boston, Massachusetts. The CSF levels of miRNA over time were compared with the occurrence of DCI, and functional outcome after 3 months. miRNAs were quantified in 427 CSF samples from 63 SAH patients in the discovery cohort, in 104 CSF samples from 63 SAH patients in the replication cohort, and in 11 CSF samples from 11 neurologically healthy patients. The miRNA profile changed remarkably immediately after SAH. Elevated miR-9-3p was associated with a poor functional outcome in the discovery cohort (p < 0.0001) after correction for multiple testing (q < 0.01) and in the replication cohort (p < 0.01). Furthermore, elevated miR-9-5p was associated with a poor functional outcome in the discovery cohort (p < 0.01) after correction for multiple testing (q < 0.05). No miRNA was associated with DCI in both cohorts. miR-9-3p and miR-9-5p are elevated in the CSF following SAH and this elevation is associated with a poor functional outcome. These elevations have potential roles in the progression of cerebral injury and could add to early prognostication.

AB - This study evaluated microRNA (miRNA) changes in cerebrospinal fluid (CSF) and their association with the occurrence of delayed cerebral ischemia (DCI) and poor functional outcome after SAH. Forty-three selected miRNAs were measured in daily CSF samples from a discovery cohort of SAH patients admitted to Rigshospitalet, Copenhagen, Denmark, and compared with neurologically healthy patients. Findings were validated in CSF from a replication cohort of SAH patients admitted to Massachusetts General Hospital, Boston, Massachusetts. The CSF levels of miRNA over time were compared with the occurrence of DCI, and functional outcome after 3 months. miRNAs were quantified in 427 CSF samples from 63 SAH patients in the discovery cohort, in 104 CSF samples from 63 SAH patients in the replication cohort, and in 11 CSF samples from 11 neurologically healthy patients. The miRNA profile changed remarkably immediately after SAH. Elevated miR-9-3p was associated with a poor functional outcome in the discovery cohort (p < 0.0001) after correction for multiple testing (q < 0.01) and in the replication cohort (p < 0.01). Furthermore, elevated miR-9-5p was associated with a poor functional outcome in the discovery cohort (p < 0.01) after correction for multiple testing (q < 0.05). No miRNA was associated with DCI in both cohorts. miR-9-3p and miR-9-5p are elevated in the CSF following SAH and this elevation is associated with a poor functional outcome. These elevations have potential roles in the progression of cerebral injury and could add to early prognostication.

KW - Cerebrospinal fluid

KW - MicroRNA

KW - Stroke

KW - Subarachnoid hemorrhage

U2 - 10.1007/s12975-020-00793-1

DO - 10.1007/s12975-020-00793-1

M3 - Journal article

C2 - 32248435

AN - SCOPUS:85082931626

VL - 11

SP - 1243

EP - 1252

JO - Translational Stroke Research

JF - Translational Stroke Research

SN - 1868-4483

ER -