Gene treatment of cerebral stroke by rAAV vector delivering IL-Ira in a rat model

In this study, we injected recombinant adeno-associated virus (rAAV) vectors expressing the interleukin-I receptor antagonist (rAAV-IL-Ira) into the cortex of rats experiencing transient cerebral ischemia. An accumulation of IL-Ira in cortical tissues of rAAVIL-Ira-injected animals was confirmed by ELISA. Triphenyltetrazolium chloride (TTC) staining of viable brain tissue revealed that the rAAV-delivered IL-Ira gene could rescue the brain tissues from ischemia-induced injury. Cortical tissues that received rAAV-IL-Ira injections had both significantly smaller total volumes of infarction as well as smaller areas of infarction on each brain slice when compared with the control models. In situ labeling analysis demonstrated significant reduction of apoptotic cells in cortical tissues rescued by rAAV-IL-Ira. Immunohistochemistry staining revealed that the rescued brain tissues contained the same levels of neuronal cells as contralateral undamaged brain tissues. These findings confirmed that the rAAV delivering the IL-Ira gene is a potential therapy for stroke.