title: Attenuation of cerebral vasospasm after subarachnoid hemorrhage in mice overexpressing extracellular superoxide dismutase.
abstract: OBJECTIVE
  Subarachnoid hemorrhage (SAH) increases production of vascular extracellular superoxide anion (*O2-). We examined whether overexpression of murine extracellular superoxide dismutase (EC-SOD) alters SAH-induced cerebral vasospasm, oxidative stress, and neurological outcome.
  
  
  METHODS
  Mice exhibiting a 2-fold increase in vascular EC-SOD and wild-type (WT) littermates were subjected to sham surgery or SAH by perforation of the right anterior cerebral artery. Neurological deficits were scored 72 hours later. Middle cerebral artery (MCA) diameter was measured or immunohistochemically stained for nitrotyrosine.
  
  
  RESULTS
  MCA diameter (mean+/-SD) was greater in EC-SOD versus WT mice after SAH but not sham surgery (EC-SOD SAH=56+/-10 microm; WT SAH=38+/-13 microm [P<0.01]; EC-SOD sham=99+/-16 microm; WT sham=100+/-15 microm). SAH decreased median (range) neurological score (scoring scale, 9 to 39; no deficit=39) versus shams, but there was no difference between EC-SOD and WT groups (EC-SOD SAH=26 [23 to 30]; WT SAH=23 [19 to 29] [P=0.27]; EC-SOD sham=39 [39]; WT sham=39 [39]). Sensory-motor deficits correlated with MCA diameter (P<0.001) but worsened primarily between 60 and 50 micro m, plateauing below this threshold. The percentage of mice with MCA nitrotyrosine staining increased after SAH in WT (sham=29%; SAH=100% [P<0.05]) but not EC-SOD (sham=33%; SAH=44% [P=0.80]) mice.
  
  
  CONCLUSIONS
  Endogenous overexpression of EC-SOD attenuated vasospasm and oxidative stress but failed to reduce neurological deficits after SAH. Extracellular *O2- likely plays a direct role in the etiology of vasospasm.
authors.affiliation: Duke University School of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: McGirt
authors.forename: Augusto
authors.initials: A
authors.lastname: Parra
authors.forename: Huaxin
authors.initials: H
authors.lastname: Sheng
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Higuchi
authors.forename: Tim D
authors.initials: TD
authors.lastname: Oury
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Laskowitz
authors.forename: Robert D
authors.initials: RD
authors.lastname: Pearlstein
authors.forename: David S
authors.initials: DS
authors.lastname: Warner
mesh_terms: D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000473:pathology; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020768:Middle Cerebral Artery / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology; D018384:Oxidative Stress / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis; D014654:Vascular Patency / Q000235:genetics; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*
chemical_list: D012333:RNA, Messenger; C002744:3-nitrotyrosine; D014443:Tyrosine; D013482:Superoxide Dismutase