title: Acetylsalicylic acid, but not clopidogrel, inhibits therapeutically induced cerebral arteriogenesis in the hypoperfused rat brain.
abstract: This study investigated the effects of acetylsalicylic acid (ASA) and clopidogrel, standardly used in the secondary prevention of vascular occlusions, on cerebral arteriogenesis in vivo and in vitro. Cerebral hypoperfusion was induced by three-vessel occlusion (3-VO) in rats, which subsequently received vehicle, ASA (6.34 mg/kg), or clopidogrel (10 mg/kg). Granulocyte colony-stimulating factor (G-CSF), which enhanced monocyte migration in an additional cell culture model, augmented cerebrovascular arteriogenesis in subgroups (40 μg/kg). Cerebrovascular reactivity and vessel diameters were assessed at 7 and 21 days. Cerebrovascular reserve capacity was completely abolished after 3-VO and remained severely compromised after 7 (-14±14%) and 21 (-5±11%) days in the ASA groups in comparison with controls (4±5% and 10±10%) and clopidogrel (4±13% and 10±8%). It was still significantly decreased when ASA was combined with G-CSF (1±4%) compared with G-CSF alone (20±8%). Posterior cerebral artery diameters confirmed these data. Monocyte migration into the vessel wall, improved by G-CSF, was significantly reduced by ASA. Acetylsalicylic acid, but not clopidogrel, inhibits therapeutically augmented cerebral arteriogenesis.
authors.affiliation: Department of Internal Medicine, Cardiology and Angiology, Richard-Thoma-Laboratories for Arteriogenesis, Center for Cardiovascular Research and Experimental and Clinical Research Center, Charité-Universitaetsmedizin Berlin, Berlin, Germany. andre.duelsner@charite.de
authors.forename: André
authors.initials: A
authors.lastname: Duelsner
authors.forename: Nora
authors.initials: N
authors.lastname: Gatzke
authors.forename: Johanna
authors.initials: J
authors.lastname: Glaser
authors.forename: Philipp
authors.initials: P
authors.lastname: Hillmeister
authors.forename: Meijing
authors.initials: M
authors.lastname: Li
authors.forename: Eun-Ji
authors.initials: EJ
authors.lastname: Lee
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lehmann
authors.forename: Daniel
authors.initials: D
authors.lastname: Urban
authors.forename: Heike
authors.initials: H
authors.lastname: Meyborg
authors.forename: Philipp
authors.initials: P
authors.lastname: Stawowy
authors.forename: Andreas
authors.initials: A
authors.lastname: Busjahn
authors.forename: Stephanie
authors.initials: S
authors.lastname: Nagorka
authors.forename: Anja Bondke
authors.initials: AB
authors.lastname: Persson
authors.forename: Ivo R
authors.initials: IR
authors.lastname: Buschmann
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D002460:Cell Line; D002533:Cerebral Angiography; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D000077144:Clopidogrel; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D010975:Platelet Aggregation Inhibitors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin