title: Neuroinflammation is Associated with Brain Extracellular TAU-Protein Release After Spontaneous Subarachnoid Hemorrhage.
abstract: BACKGROUND
  Animal data suggest an association between neuroinflammation and secondary brain injury including axonal injury after aneurysmal subarachnoid hemorrhage (aSAH). We sought to study the association between brain extracellular interleukin (IL)-6 and TAU-protein levels as a surrogate marker for neuroinflammation and axonal injury in patients with poor grade aSAH.
  
  
  METHODS
  Prospectively collected data from 26 consecutive poor-grade aSAH patients with multimodal neuromonitoring including cerebral microdialysis (CMD) were retrospectively analyzed. IL-6 and TAU-protein levels were analyzed using ELISA from a single CMD-sample every 24 hours and correlated with brain metabolic and hemodynamic parameters. Patients were dichotomized to highgrade (N=10) or low-grade (N=16) neuroinflammation according to their median CMD-IL-6 levels. Data were analyzed using generalized estimating equations to account for multiple within-subject measurements.
  
  
  RESULTS
  Perilesional probe location (P=0.02) and aSAH related intracerebral hemorrhage (aICH) volume (P=0.003) at admission were associated with high-grade neuroinflammation. Brain extracellular TAU-protein levels (P=0.001), metabolic distress and delayed cerebral infarction (DCI; P=0.001) were linked to high-grade neuroinflammation. Relative or absolute phosphor-TAU levels were not correlated with CMD-IL-6 levels. High-grade neuroinflammation was a predictor for worse outcome three months after ictus, independently from probe location, initial Hunt&amp;Hess grade and age (P=0.01).
  
  
  CONCLUSIONS
  Neuroinflammation after aSAH is associated with intraparenchymal bleeding, deranged cerebral metabolism and TAU-protein release. The impact of potential anti-inflammatory treatment strategies on secondary brain injury after aSAH has to be investigated in future studies.
authors: Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
authors: Alois Josef
authors: AJ
authors: Schiefecker
authors: Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
authors: Anelia
authors: A
authors: Dietmann
authors: Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
authors: Ronny
authors: R
authors: Beer
authors: Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
authors: Bettina
authors: B
authors: Pfausler
authors: Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
authors: Peter
authors: P
authors: Lackner
authors: Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
authors: Mario
authors: M
authors: Kofler
authors: Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
authors: Marlene
authors: M
authors: Fischer
authors: Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
authors: Gregor
authors: G
authors: Broessner
authors: Department of Neurosurgery, Medical University of Innsbruck, Innsbruck, Austria.
authors: Florian
authors: F
authors: Sohm
authors: Department of Neurosurgery, Medical University of Innsbruck, Innsbruck, Austria.
authors: Miriam
authors: M
authors: Mulino
authors: Department of Neurosurgery, Medical University of Innsbruck, Innsbruck, Austria.
authors: Claudius
authors: C
authors: Thomé
authors: Laboratory for Experimental Alzheimer's Research, Department of Psychiatry and Psychotherapy, Medical University of Innsbruck, Innsbruck, Austria.
authors: Christian
authors: C
authors: Humpel
authors: Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
authors: Erich
authors: E
authors: Schmutzhard
authors: Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria.
authors: Raimund
authors: R
authors: Helbok
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D010766:Phosphorylation; D011379:Prognosis; D012189:Retrospective Studies; D013345:Subarachnoid Hemorrhage / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D016875:tau Proteins
keywords: Neuroinflammation; cerebral microdialysis; interleukin-6; intracerebral hemorrhage; tau protein