Gene transfer of extracellular superoxide dismutase failed to prevent cerebral vasospasm after experimental subarachnoid hemorrhage.
OBJECTIVE
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.


METHODS
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.
Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.
Mitsuo
M
Yamaguchi
Changman
C
Zhou
Donald D
DD
Heistad
Yoshimasa
Y
Watanabe
John H
JH
Zhang
D000256:Adenoviridae; D000818:Animals; D001488:Basilar Artery / Q000473:pathology; D004195:Disease Models, Animal; D004285:Dogs; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D013345:Subarachnoid Hemorrhage / Q000628:therapy*; D013482:Superoxide Dismutase / Q000235:genetics*; D019076:Transgenes; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000517:prevention & control*
D013482:Superoxide Dismutase