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(Stroke. 2002;33:2317.)
© 2002 American Heart Association, Inc.

Original Contributions

Attenuation of Cerebral Vasospasm After Subarachnoid Hemorrhage in Mice Overexpressing Extracellular Superoxide Dismutase

Matthew J. McGirt, BS; Augusto Parra, MD, MPH; Huaxin Sheng, MD; Yoshinori Higuchi, MD, PhD; Tim D. Oury, MD, PhD; Daniel T. Laskowitz, MD; Robert D. Pearlstein, PhD David S. Warner, MD

From Duke University School of Medicine (M.J.M.) and Departments of Medicine (A.P., D.T.L.), Anesthesiology (H.S., D.S.W.), and Surgery (R.D.P., D.S.W.), Duke University Medical Center, Durham, NC; Department of Radiation Medicine, Loma Linda University Medical Center, Loma Linda, Calif (Y.H.); and Department of Pathology, University of Pittsburgh, Pittsburgh, Pa (T.D.O.).

Correspondence to David S. Warner, MD, Department of Anesthesiology, Duke University Medical Center, Box 3094 DUMC, Durham, NC 27710. E-mail warne002{at}mc.duke.edu

Background and Purpose— 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 µm; WT SAH=38±13 µm [P<0.01]; EC-SOD sham=99±16 µm; WT sham=100±15 µm). 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 µm, 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.

Key Words: extracellular space • mice • mice, transgenic • subarachnoid hemorrhage • superoxide dismutase • vasospasm

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