title: Cerebral Artery Remodeling in Rodent Models of Subarachnoid Hemorrhage.
abstract: Vasospasm is known to contribute to delayed cerebral ischemia following subarachnoid hemorrhage (SAH). We hypothesized that vasospasm initiates structural changes within the vessel wall, possibly aggravating ischemia and leading to resistance to vasodilator treatment. We therefore investigated the effect of blood on cerebral arteries with respect to contractile activation and vascular remodeling. In vitro experiments on rodent basilar and middle cerebral arteries showed a gradual contraction in response to overnight exposure to blood. After incubation with blood, a clear inward remodeling was found, reducing the caliber of the passive vessel. The transglutaminase inhibitor L682.777 fully prevented this remodeling. Translation of the in vitro findings to an in vivo SAH model was attempted in rats, using both a single prechiasmatic blood injection model and a double cisterna magna injection model, and in mice, using a single prechiasmatic blood injection. However, we found no substantial changes in active or passive biomechanical properties in vivo. We conclude that extravascular blood can induce matrix remodeling in cerebral arteries, which reduces vascular caliber. This remodeling depends on transglutaminase activity. However, the current rodent SAH models do not permit in vivo confirmation of this mechanism.
authors.forename: Bilge
authors.initials: B
authors.lastname: Guvenc Tuna
authors.forename: Nadia
authors.initials: N
authors.lastname: Lachkar
authors.forename: Judith
authors.initials: J
authors.lastname: de Vos
authors.forename: Erik N T P
authors.initials: EN
authors.lastname: Bakker
authors.forename: Ed
authors.initials: E
authors.lastname: VanBavel
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001783:Blood Flow Velocity; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D017208:Rats, Wistar; D012039:Regional Blood Flow; D013345:Subarachnoid Hemorrhage / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D066253:Vascular Remodeling / Q000187:drug effects; D014661:Vasoconstriction; D020301:Vasospasm, Intracranial / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*
chemical_list: D004791:Enzyme Inhibitors; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins