Endothelial nitric oxide synthase-11R protein therapy for prevention of cerebral vasospasm in rats: A preliminary report

In one of our studies we found that enhanced green fluorescent protein (EGFP) fused with consecutive 11 arginines (11R), one of the protein transduction domains (PTDs) [1-6, 11], and effectively penetrated into all layers of the rat basilar artery (BA). We examined whether eNOS (140-kDa) fused 11R (11R-eNOS) was also transduced into the BAs and had a positive effect on the attenuation of cerebral vasospasm. 11R-eNOS or saline was injected into the cisterna magna of male Sprague-Dawley rats. Two hours after the injection, the BAs were extracted from the rats and transduction efficacy of 11R-eNOS in the BA was evaluated by immunofluorescence staining. To examine the effect of 11R-eNOS on the cerebral arteries exposed to SAH, we measured the post SAH BA diameters six hours after the injection of 11R-eNOS. Immunofluorescent study confirmed the presence of 11R-eNOS protein in the layers of the cerebral arteries in vivo. 11R-eNOS had a positive effect on attenuation of cerebral vasospasm. 11R-eNOS was effectively transduced into the walls of the BA. 11R-eNOS inhibited the vasoconstriction after SAH. These results suggest that 11R-eNOS protein therapy has a potential in treating cerebral vasospasm.