title: Detection and quantification of microRNA in cerebral microdialysate.
abstract: BACKGROUND
  Secondary brain injury accounts for a major part of the morbidity and mortality in patients with spontaneous aneurysmal subarachnoid hemorrhage (SAH), but the pathogenesis and pathophysiology remain controversial. MicroRNAs (miRNAs) are important posttranscriptional regulators of complementary mRNA targets and have been implicated in the pathophysiology of other types of acute brain injury. Cerebral microdialysis is a promising tool to investigate these mechanisms. We hypothesized that miRNAs would be present in human cerebral microdialysate.
  
  
  METHODS
  RNA was extracted and miRNA profiles were established using high throughput real-time quantification PCR on the following material: 1) Microdialysate sampled in vitro from A) a solution of total RNA extracted from human brain, B) cerebrospinal fluid (CSF) from a neurologically healthy patient, and C) a patient with SAH; and 2) cerebral microdialysate and CSF sampled in vivo from two patients with SAH. MiRNAs were categorized according to their relative recovery (RR) and a pathway analysis was performed for miRNAs exhibiting a high RR in vivo.
  
  
  RESULTS
  Seventy-one of the 160 miRNAs detected in CSF were also found in in vivo microdialysate from SAH patients. Furthermore specific miRNAs consistently exhibited either a high or low RR in both in vitro and in vivo microdialysate. Analysis of repeatability showed lower analytical variation in microdialysate than in CSF.
  
  
  CONCLUSIONS
  MiRNAs are detectable in cerebral microdialysate; a large group of miRNAs consistently showed a high RR in cerebral microdialysate. Measurement of cerebral interstitial miRNA concentrations may aid in the investigation of secondary brain injury in neurocritical conditions.
authors.affiliation: Department of Neuroanaesthesiology, The Neuroscience Centre, Copenhagen University Hospital, Copenhagen, Denmark. bache@dadlnet.dk.|Centre for Genomic Medicine, The Diagnostic Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. bache@dadlnet.dk.
authors.forename: Søren
authors.initials: S
authors.lastname: Bache
authors.affiliation: Department of Neurosurgery, The Neuroscience Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. rune333@gmail.com.
authors.forename: Rune
authors.initials: R
authors.lastname: Rasmussen
authors.affiliation: Centre for Genomic Medicine, The Diagnostic Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. rossing.maria@gmail.com.
authors.forename: Maria
authors.initials: M
authors.lastname: Rossing
authors.affiliation: Department of Neuroanaesthesiology, The Neuroscience Centre, Copenhagen University Hospital, Copenhagen, Denmark. nahammer@hotmail.com.
authors.forename: Niels Risør
authors.initials: NR
authors.lastname: Hammer
authors.affiliation: Department of Neurosurgery, The Neuroscience Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. marianne.juhler@gmail.com.
authors.forename: Marianne
authors.initials: M
authors.lastname: Juhler
authors.affiliation: Centre for Genomic Medicine, The Diagnostic Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. ejf@regionsjaelland.dk.|Present address: Department of Clinical Biochemistry, Naestved Sygehus, Naestved, Denmark. ejf@regionsjaelland.dk.
authors.forename: Lennart
authors.initials: L
authors.lastname: Friis-Hansen
authors.affiliation: Centre for Genomic Medicine, The Diagnostic Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. finn.cilius.nielsen@regionh.dk.
authors.forename: Finn Cilius
authors.initials: FC
authors.lastname: Nielsen
authors.affiliation: Department of Neuroanaesthesiology, The Neuroscience Centre, Copenhagen University Hospital, Copenhagen, Denmark. kirsten.moller@dadlnet.dk.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Møller
mesh_terms: D001921:Brain / Q000378:metabolism; D001930:Brain Injuries / Q000134:cerebrospinal fluid; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D006801:Humans; D035683:MicroRNAs / Q000134:cerebrospinal fluid*; D017551:Microdialysis / Q000379:methods*; D010477:Perfusion; D012323:RNA Processing, Post-Transcriptional; D015203:Reproducibility of Results; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid*; D013696:Temperature; D016896:Treatment Outcome
chemical_list: D035683:MicroRNAs