title: Solulin reduces infarct volume and regulates gene-expression in transient middle cerebral artery occlusion in rats.
abstract: BACKGROUND
  Thrombolysis after acute ischemic stroke has only proven to be beneficial in a subset of patients. The soluble recombinant analogue of human thrombomodulin, Solulin, was studied in an in vivo rat model of acute ischemic stroke.
  
  
  METHODS
  Male SD rats were subjected to 2 hrs of transient middle cerebral artery occlusion (tMCAO). Rats treated with Solulin intravenously shortly before reperfusion were compared to rats receiving normal saline i.v. with respect to infarct volumes, neurological deficits and mortality. Gene expression of IL-6, IL-1β, TNF-α, MMP-9, CD11B and GFAP were semiquantitatively analyzed by rtPCR of the penumbra.
  
  
  RESULTS
  24 hrs after reperfusion, rats were neurologically tested, euthanized and infarct volumes determined. Solulin significantly reduced mean total (p=0.001), cortical (p=0.002), and basal ganglia (p=0.036) infarct volumes. Hippocampal infarct volumes (p=0.191) were not significantly affected. Solulin significantly downregulated the expression of IL-1β (79%; p<0.001), TNF-α (59%; p=0.001), IL-6 (47%; p=0.04), and CD11B (49%; p=0.001) in the infarcted cortex compared to controls.
  
  
  CONCLUSIONS
  Solulin reduced mean total, cortical and basal ganglia infarct volumes and regulated a subset of cytokines and proteases after tMCAO suggesting the potency of this compound for therapeutic interventions.
authors.affiliation: Department of Neurosurgery, Klinikum rechts der Isar, Hospital of the Technical University Munich, Ismaningerstr, 22, 81675 Munich, Germany. yu.ryang@lrz.tum.de
authors.forename: Yu-Mi
authors.initials: YM
authors.lastname: Ryang
authors.forename: Jon
authors.initials: J
authors.lastname: Dang
authors.forename: Markus
authors.initials: M
authors.lastname: Kipp
authors.forename: Karl-Uwe
authors.initials: KU
authors.lastname: Petersen
authors.forename: Astrid V
authors.initials: AV
authors.lastname: Fahlenkamp
authors.forename: Jens
authors.initials: J
authors.lastname: Gempt
authors.forename: Dominik
authors.initials: D
authors.lastname: Wesp
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.forename: Cordian
authors.initials: C
authors.lastname: Beyer
authors.forename: Mark
authors.initials: M
authors.lastname: Coburn
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018179:Receptors, Thrombin / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D018696:Neuroprotective Agents; D018179:Receptors, Thrombin; D011994:Recombinant Proteins; C558438:solulin protein
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