Direct protein transduction method to cerebral arteries by using 11R: New strategy for the treatment of cerebral vasospasm after subarachnoid haemorrhage

Gene transfer with some vectors may be useful for treatment of cerebral vasospasm after subarachnoid haemorrhage (SAH) [2, 3, 6, 10, 12, 13, 19]. However, this method has some safety problems [18]. Previous studies have shown that direct delivery of therapeutic proteins by using protein transduction domain (PTD) may reduce these problems [14, 15]. Here, we examined the transduction efficiency of eleven consecutive arginines (11R), which is one of the most effective PTD [8, 9], into the rat cerebral arteries by using 11R-enhanced-green fluorescent protein (11R-EGFP). 11R-EGFP or EGFP was injected into the cisterna magna of the rats with SAH. SAH model was made by autologous blood injection. The proteins were injected just after the autologous blood injection in SAH rats. The expression of 11R-EGFP or EGFP was observed by fluorescence microscope. The signal of 11R-EGFP was much stronger than that of EGFP in all the layers of the rat basilar artery (BA). The 11R-EGFP was especially transduced into the tunica media of the basilar artery 2 h after the injection. Our results demonstrate that 11R-fused fluorescent protein effectively penetrates into the all layers of the rat BA, and especially into the tunica media.