title: Experimental subarachnoid hemorrhage causes early and long-lasting microarterial constriction and microthrombosis: an in-vivo microscopy study.
abstract: Early brain injury (EBI) after subarachnoid hemorrhage (SAH) is characterized by a severe, cerebral perfusion pressure (CPP)-independent reduction in cerebral blood flow suggesting alterations on the level of cerebral microvessels. Therefore, we aimed to use in-vivo imaging to investigate the cerebral microcirculation after experimental SAH. Subarachnoid hemorrhage was induced in C57/BL6 mice by endovascular perforation. Pial arterioles and venules (10 to 80 μm diameter) were examined using in-vivo fluorescence microscopy, 3, 6, and 72 hours after SAH. Venular diameter or flow was not affected by SAH, while >70% of arterioles constricted by 22% to 33% up to 3 days after hemorrhage (P<0.05 versus sham). The smaller the investigated arterioles, the more pronounced the constriction (r(2)=0.92, P<0.04). Approximately 30% of constricted arterioles were occluded by microthrombi and the frequency of arteriolar microthrombosis correlated with the degree of constriction (r(2)=0.93, P<0.03). The current study demonstrates that SAH induces microarterial constrictions and microthrombosis in vivo. These findings may explain the early CPP-independent decrease in cerebral blood flow after SAH and may therefore serve as novel targets for the treatment of early perfusion deficits after SAH.
authors.affiliation: Institute for Surgical Research, University of Munich Medical Center-Großhadern, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Friedrich
authors.forename: Frank
authors.initials: F
authors.lastname: Müller
authors.forename: Sergej
authors.initials: S
authors.lastname: Feiler
authors.forename: Karsten
authors.initials: K
authors.lastname: Schöller
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Plesnila
mesh_terms: D000818:Animals; D001160:Arterioles / Q000503:physiopathology; D002536:Cerebral Arteries / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D020767:Intracranial Thrombosis / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000502:physiology; D008856:Microscopy, Fluorescence; D055806:Microvessels / Q000503:physiopathology*; D010841:Pia Mater / Q000098:blood supply; D012720:Severity of Illness Index; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000503:physiopathology; D014661:Vasoconstriction / Q000502:physiology*