Published Online
on October 7, 2004

A more recent version of this article appeared on November 1, 2004

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Submitted on June 1, 2004
Revised on August 3, 2004
Accepted on August 23, 2004

Gene Transfer of Extracellular Superoxide Dismutase Failed to Prevent Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage

Mitsuo Yamaguchi MD; Changman Zhou MD, PhD; Donald D. Heistad MD; Yoshimasa Watanabe MD; and John H. Zhang MD, PhD^*

From the Department of Neurosurgery (M.Y., C.Z., J.H.Z.), Louisiana State University Health Sciences Center, Shreveport, La; and the Department of Internal Medicine (D.D.H., Y.W.), University of Iowa, Iowa City.

^* To whom correspondence should be addressed. E-mail: johnzhang3910{at}yahoo.com.

Background and Purpose--We examined the therapeutic effect of human extracellular superoxide dismutase (ECSOD) gene transfer in the prevention of delayed cerebral vasospasm after experimental subarachnoid hemorrhage (SAH) because it was reported ECSOD relieved early-stage vasospasm.

Method--Twenty mongrel dogs were divided randomly into 4 groups to serve as control, SAH, SAH+adenovirus ECSOD (AdECSOD), and SAH+no transgene (AdBglII) groups, respectively. An established canine double-hemorrhage model of SAH was used by injecting autologous arterial blood into the cisterna magna on day 0 and day 2. Angiography was performed at day 0 and day 7. Clinical behavior, cerebrospinal fluid (CSF) ECSOD activity, CSF leukocyte count, morphology, and human ECSOD expression (RT-PCR) in the basilar arteries were evaluated.

Results--Severe vasospasm was obtained in SAH, SAH+AdECSOD, and SAH+AdBglII gene-transferred dogs, and the residual diameters of the basilar artery were 41±1%, 39±4%, and 49±4%, respectively. Increased CSF activity of ECSOD was obtained in SAH+AdECSOD (162±23 U/mL) when compared with SAH (26±2) and SAH+AdBglII (25±3) dogs. RT-PCR confirmed successful gene transfer in the basilar arteries from SAH+AdECSOD dogs. Increased leukocyte counts were observed in the CSF and in the subarachnoid space, especially in SAH+AdECSOD and SAH+AdBglII dogs.

Conclusions--Gene transfer of human ECSOD failed to prevent delayed cerebral vasospasm.

Key words: cerebral vasospasm • gene therapy • subarachnoid hemorrhage

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