Postischemic Intraventricular Administration of FGF-2-Expressing Adenoviral Vectors Improves Neurological Outcome and Reduces Infarct Volume after Permanent Focal Cerebral Ischemia in Rats

Recently, we showed that the intraventricular administration of fibroblast growth factor (FGF) 2-expressing adenoviral vectors (AxCAMAssFGF-2) improves neurological recovery and reduces infarct volume after transient middle cerebral artery occlusion (MCAO) in rats. In the present study, we investigated whether the intraventricular administration of FGF-2-expressing adenoviral vectors has the same effect after permanent MCAO in rats. Infection of in vitro-cultured cells with AxCAMAssFGF-2, which contain an externally fused secretory signal of interleukin-2, results in an approximately 10-fold higher secretion of FGF-2 compared to infection with AxCAJSFGF-2, which contains no secretory signal. AxCAMAssFGF-2 was injected intraventricularly 2 hours after permanent MCAO. The treatment group showed significant recovery compared with the nontreatment group in terms of serial neurological severity scores (NSS) at 14, 21, 28 and 35 days after MCAO. Furthermore, 2,3,5-triphenyltetrazolium chloride staining showed that infarct volume was significantly reduced by the intraventricular administration of AxCAMAssFGF-2 in comparison with that of untreated MCAO. These results suggest that FGF-2 gene transfer using adenoviral vectors is useful in the treatment of occlusive cerebrovascular disease, regardless of reperfusion.