title: Cerebral Taurine Levels are Associated with Brain Edema and Delayed Cerebral Infarction in Patients with Aneurysmal Subarachnoid Hemorrhage.
abstract: BACKGROUND
  Cerebral edema and delayed cerebral infarction (DCI) are common complications after aneurysmal subarachnoid hemorrhage (aSAH) and associated with poor functional outcome. Experimental data suggest that the amino acid taurine is released into the brain extracellular space secondary to cytotoxic edema and brain tissue hypoxia, and therefore may serve as a biomarker for secondary brain injury after aSAH. On the other hand, neuroprotective mechanisms of taurine treatment have been described in the experimental setting.
  
  
  METHODS
  We analyzed cerebral taurine levels using high-performance liquid chromatography in the brain extracellular fluid of 25 consecutive aSAH patients with multimodal neuromonitoring including cerebral microdialysis (CMD). Patient characteristics and clinical course were prospectively recorded. Associations with CMD-taurine levels were analyzed using generalized estimating equations with an autoregressive process to handle repeated observations within subjects.
  
  
  RESULTS
  CMD-taurine levels were highest in the first days after aSAH (11.2 ± 3.2 µM/l) and significantly decreased over time (p < 0.001). Patients with brain edema on admission or during hospitalization (N = 20; 80 %) and patients developing DCI (N = 5; 20 %) had higher brain extracellular taurine levels compared to those without (Wald = 7.3, df = 1, p < 0.01; Wald = 10.1, df = 1, p = 0.001, respectively) even after adjusting for disease severity and CMD-probe location. There was no correlation between parenteral taurine supplementation and brain extracellular taurine (p = 0.6). Moreover, a significant correlation with brain extracellular glutamate (r = 0.82, p < 0.001), lactate (r = 0.56, p < 0.02), pyruvate (r = 0.39, p < 0.01), potassium (r = 0.37, p = 0.01), and lactate-to-pyruvate ratio (r = 0.24, p = 0.02) was found.
  
  
  CONCLUSIONS
  Significantly higher CMD-taurine levels were found in patients with brain edema or DCI after aneurysmal subarachnoid hemorrhage. Its value as a potential biomarker deserves further investigation.
authors.affiliation: Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. Mario.Kofler@i-med.ac.at.
authors.forename: Mario
authors.initials: M
authors.lastname: Kofler
authors.affiliation: Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. Alois.Schiefecker@uki.at.
authors.forename: Alois
authors.initials: A
authors.lastname: Schiefecker
authors.affiliation: CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Str. 65, 88397, Biberach an der Riss, Germany. Boris.Ferger@boehringer-ingelheim.com.
authors.forename: Boris
authors.initials: B
authors.lastname: Ferger
authors.affiliation: Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. Ronny.Beer@i-med.ac.at.
authors.forename: Ronny
authors.initials: R
authors.lastname: Beer
authors.affiliation: Department of Neurosurgery, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. Florian.Sohm@uki.at.
authors.forename: Florian
authors.initials: F
authors.lastname: Sohm
authors.affiliation: Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. Gregor.Broessner@uki.at.
authors.forename: Gregor
authors.initials: G
authors.lastname: Broessner
authors.affiliation: UMIT - University for Health Sciences, Medical Informatics and Technology, Eduard-Wallnöfer-Zentrum 1, 6060, Hall, Austria. Werner.Hackl@umit.at.
authors.forename: Werner
authors.initials: W
authors.lastname: Hackl
authors.affiliation: Department of Radiology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. Paul.Rhomberg@uki.at.
authors.forename: Paul
authors.initials: P
authors.lastname: Rhomberg
authors.affiliation: Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. Peter.Lackner@uki.at.
authors.forename: Peter
authors.initials: P
authors.lastname: Lackner
authors.affiliation: Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. Bettina.Pfausler@uki.at.
authors.forename: Bettina
authors.initials: B
authors.lastname: Pfausler
authors.affiliation: Department of Neurosurgery, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. Claudius.Thome@uki.at.
authors.forename: Claudius
authors.initials: C
authors.lastname: Thomé
authors.affiliation: Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. Erich.Schmutzhard@i-med.ac.at.
authors.forename: Erich
authors.initials: E
authors.lastname: Schmutzhard
authors.affiliation: Neurological Intensive Care Unit, Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. Raimund.Helbok@uki.at.
authors.forename: Raimund
authors.initials: R
authors.lastname: Helbok
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism*; D002544:Cerebral Infarction / Q000209:etiology / Q000378:metabolism*; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D002532:Intracranial Aneurysm / Q000150:complications / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D064847:Multimodal Imaging; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000378:metabolism*; D013654:Taurine / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D013654:Taurine
keywords: Aminoacids; Cerebral microdialysis; Multimodal neuromonitoring; Subarachnoid hemorrhage; Taurine