title: Association of dimethylarginines and mediators of inflammation after acute ischemic stroke.
abstract: Elevated levels of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are accompanied by endothelial dysfunction and predict adverse outcome after ischemic stroke. Via induction of oxidative stress, dimethylarginines are possibly linked to the inflammatory cascade after stroke that is known to considerably contribute to secondary progression of brain injury. We sought to investigate the association between dimethylarginines and inflammatory mediators in patients with acute ischemic stroke.
  
  
  
  Plasma levels of ADMA and SDMA were measured in prospectively collected blood samples of 58 patients with acute ischemic stroke. Blood samples were taken at 6 hours, 12 hours, 24 hours, 3 days and 7 days after onset of symptoms. Analyses of ADMA and SDMA were done by high-performance liquid chromatography-tandem mass spectrometry. Monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), interleukin-6 (IL-6), C-reactive protein (CRP) and S100B as markers of inflammation and brain damage were determined by commercially available immunometric assays. Patient data were compared with control data from 32 age-adjusted healthy volunteers. Baseline stroke severity was evaluated by the National Institutes of Health Stroke Scale (NIHSS) (NIHSS 0 to 1: mild stroke; NIHSS 2 to 8: moderate stroke; NIHSS ≥9: severe stroke).
  
  
  
  Plasma ADMA and SDMA levels significantly correlated with blood levels of inflammatory mediators up to day 7 after stroke. On multiple stepwise linear regression analysis ADMA correlated with TIMP-1 at 6 hours, 24 hours, 3 days and 7 days, MMP-9 at 12 hours and IL-6 at 7 days (P <0.05) while SDMA correlated with MCP-1 at 6 hours, 24 hours, 3 days and 7 days as well as IL-6 at 3 days and 7 days (P <0.05).
  
  
  
  The levels of the vasoactive compound ADMA as well as levels of its structural isomer SDMA are associated with levels of inflammatory mediators after acute ischemic stroke. Further studies need to elucidate the cause and effect relationship of these crucial players.
authors.affiliation: Department of Neurology, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30623, Germany.
authors.forename: Shufen
authors.initials: S
authors.lastname: Chen
authors.forename: Jens
authors.initials: J
authors.lastname: Martens-Lobenhoffer
authors.forename: Karin
authors.initials: K
authors.lastname: Weissenborn
authors.forename: Jan T
authors.initials: JT
authors.lastname: Kielstein
authors.forename: Ralf
authors.initials: R
authors.lastname: Lichtinghagen
authors.forename: Milani
authors.initials: M
authors.lastname: Deb-Chatterji
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Anita B
authors.initials: AB
authors.lastname: Tryc
authors.forename: Annemarie
authors.initials: A
authors.lastname: Goldbecker
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dong
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Bode-Böger
authors.forename: Hans
authors.initials: H
authors.lastname: Worthmann
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D018932:Chemokine CCL2 / Q000097:blood; D015331:Cohort Studies; D003711:Demyelinating Diseases / Q000097:blood* / Q000209:etiology*; D004660:Encephalitis / Q000097:blood* / Q000209:etiology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood; D012189:Retrospective Studies; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D013223:Statistics as Topic; D020521:Stroke / Q000097:blood / Q000150:complications*; D013997:Time Factors
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D002097:C-Reactive Protein