Plasmid pLXSN-Mediated Adrenomedullin Gene Therapy for Cerebral Vasospasm Following Subarachnoid Hemorrhage in Rats.

Abstract

BackgroundThe aim of this study was to investigate the protective effect of ADM gene mediated by plasmid pVAX1 on cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH).Material/MethodsThe recombinant plasmid pVAX-ADM was successfully established, and 40 SD rats were randomly divided into normal saline, pVAX1, pVAX1-ADM low-dose, pVAX1-ADM mid-dose, and pVAX1-ADM high-dose groups. The circumference and diameter of basilar artery, diameter of middle cerebral artery and internal carotid artery, and thickness of basilar artery wall were observed. The levels of circulating endothelial cells (CEC) and levels of regional cerebral blood flow (rCBF) of the parietal cortex were detected at different time-points. The expression levels of serum ADM, ET-1, and NOS of each group and the neurological functions were compared.ResultsThe circumference and diameter of basilar artery and the diameter of the middle cerebral artery and internal carotid artery in pVAX1-ADM groups were significantly longer than those in the saline group and pVAX1 group (P<0.05), but the thickness of the basilar artery wall in pVAX1-ADM groups was significantly lower (P<0.05), and the levels of growth or decrease were both dose-dependent (P<0.05). Compared with the saline group and pVAX1 group, the expression levels of serum ADM, NOS, and rCBF in pVAX1-ADM groups were significantly higher (P<0.05), but the levels of serum ET-1 and CEC were significantly lower (P<0.05). The scores of neurobehavioral functions of pVAX1-ADM groups were significantly lower (P<0.05), and the scores were also dose-dependent (P<0.05).ConclusionsThe recombinant eukaryotic expression plasmid pVAX1-ADM can significantly relieve cerebral vasospasm, increase the expression of serum ADM and NOS, and decrease the expression of serum ET-1 in a rat model of CVS; it is dose-dependent and can also improve nervous system function.