Brain ischemia augments exo-focal transgene expression of adenovirus-mediated gene transfer to ependyma in hypertensive rats

The ependyma is one of the feasible targets for gene transfer to the brain. Using two different replication-deficient recombinant adenoviral vectors, AdCMVβGal or AdRSVIL10, we examined effects of cortical brain ischemia on transgene expression in the ependyma after administration of the vector into the lateral ventricle of spontaneously hypertensive rats (SHR). Expression of the reporter gene lacZ at the lateral ventricle was detected by histochemistry for semiquantitative scoring or by biochemical assay for quantitative analysis. Ependymal cells in the ventricles expressed the transgene as early as 6 h after gene transfer in both sham treatment and ischemia treatment. In the sham treatment, the expression peaked at 12 h and slowly decreased toward day 4 and day 7. However, transgene expressions in the ischemic brain on day 4 and day 7 were significantly higher than sham treatment. In the biochemical assay, β-galactosidase activity detected on day 4 at the periventricular area of the ischemic group (37 ± 9 mU/mg protein) was significantly greater than that of the sham group (12 ± 4, P < 0.01). In the enzyme-linked immunosorbent assay for gene transfer of interleukin-10 (IL-10), IL-10 in the cerebrospinal fluid (CSF) of the ischemic group (11,633 ± 4322 pg/ml) was significantly greater than that in the sham group (2460 ± 1486, P < 0.05) on day 5. These results suggest that transgene expression in the exo-focal remote area of ependyma is augmented by cortical ischemia, and the ependyma may be a promising target of gene transfer of brain ischemia.