Gene therapy against ischemic stroke targeting inflammatory signals

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Gene therapy may be a promising approach for treatment of brain ischemia although efficiency of post-ischemic gene therapy is not established. Our goal in this study was to examine effects of gene transfer of interleukin-10 (IL-10), an anti-inflammatory cytokine, after induction of brain ischemia. Brain ischemia was produced by photochemical occlusion of distal middle cerebral artery in spontaneously hypertensive rats. Ninety minutes after focal ischemia, adenoviral vectors encoding human IL-10 (AdIL10) or β-galactosidase (control) were injected into the lateral ventricle. Five days after ischemia, IL-10 in the CSF, infarct volume, infiltrations of leukocytes/macrophages in the infarct area were determined. The transduced IL-10 was released to the CSF from the ventricular wall and increased 5 days after AdIL 10 transfection. Cerebral blood flow during ischemia was not different between both treatment. Brain infarction of AdIL 10 group was significantly smaller and infiltrations of leukocytes and macrophages were fewer in the IL-10 treatment than control. In conclusion, post-ischemic gene transfer of IL-10 into the lateral ventricle significantly attenuated brain infarction, suggesting gene transfer of IL-10 as a promising approach for treatment of brain ischemia.